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Teratogens are substances that my cause birth defects and has a toxic effect on the embryo and fetus (Tantibanchai, 2014)
Some examples of Teratogens are Thalimide, Mercury and PCBS.

Teratogens cause damage to the baby during critical/sensitive. For example: Day 44 there is a hand shape then day 50 fingers between to develop. Around this time is where a tertogen such as thalimide could affect the arms and leg development (Atchinson, 2014).
In order to prevent teratogens early on is to due to a preliminary testing before being prescribed contraception (Gov, 2019).

Sources:
https://embryo.asu.edu/pages/teratogens
https://www.gov.uk/drug-safety-update/medicines-with-teratogenic-potential-what-is-effective-contraception-and-how-often-is-pregnancy-testing-needed
https://youtu.be/6BH0ntPfDrs

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Different teratogens affect children differently, for example: birth defects, physical abnormalities, heart defects, disorders, lower IQ, mental impairment, neural defects.

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the factors of Teratogens are:
The timing of exposure.
The amount of exposure.
The number of teratogons.
Genetics.
Being male or female.

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Some information about the background of teratogens, some types of them and a timeline of effects - https://www.osmosis.org/answers/teratogen

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A teratogen is any agent that causes an abnormality following fetal exposure during pregnancy. Teratogens are usually discovered after an increased prevalence of a particular birth defect. For example, in the early 1960’s, a drug known as thalidomide was used to treat morning sickness. Exposure of the fetus during this early stage of development resulted in cases of phocomelia, a congenital malformation in which the hands and feet are attached to abbreviated arms and legs.https://www.ncbi.nlm.nih.gov/books/NBK132140/

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Common teratogens..
Medications.
Social exposures.
Infections.
Physical exposures.
Environmental agents.

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Teratogens are substances that cause abnormalities to fetal development. They have the ability to affect the fetus 10-14 days after conception.

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This website is useful for having a clear definition of what teratogens are.
https://www.osmosis.org/answers/teratogen

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How can teratogens affect babies at which stage?
https://www.stanfordchildrens.org/en/topic/default?id=teratogens-overview-90-P09519

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https://d16qt3wv6xm098.cloudfront.net/RO5kRJraTUecKbBuCFJWH6g9QiKDaSf_/_.png.
This is an image of different types of teratogens, the background of them and the timeline effects.

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https://www.healthline.com/health/pregnancy/teratogens

Teratogens are drugs, chemicals, or infections that can cause abnormal fetal development. Approximately 4-5% of birth defects are caused by exposure to a teratogen. Researchers believe a teratogen can affect a developing fetus about 10 to14 days after conception.

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http://www.knowledge.scot.nhs.uk/ecomscormplayer/fasd//Understanding3.pdf

(NHS, 2013)
Extreme harm teratogens can cause is death, i.e. through miscarriage or, less frequently, very early delivery or stillbirth. Teratogenic agents, by definition, are able to produce a wide range of fetal abnormalities and birth defects.

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Teratogens are 'compounds and environmental conditions which interfere with normal in utero development.' (Hall, 2016)
J.G. Hall, (2016)

Pediatric Diseases and Epigenetics. Available at: https://www.sciencedirect.com/science/article/pii/B9780128032398000235. Date accessed 16/02/2021.

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Part of this book has info on teratogenics and some stuff for pregnancy that we have looked at. From page 105.

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This introductory text addresses the principles and mechanisms of toxicology as applied to environmentally-encountered toxic agents. Each chapter concludes with review questions that may be used for student self-testing and topics covered include dose response, hazards and risk assessment, determination of toxicity, pesticides, metals, plastics, organic solvents, environmental carcinogens, teratogens and mutagens

Published Washington, D.C.; London: Taylor & Francis, 1996

This resource is available electronically from the following locations

Copies on shelf at E-Resource.

Details

Statement of responsibility: W. William Hughes

Physical Description: xii,176p. : ill. ; 26 cm.

Subject: Environmental toxicology.; Environment Pollution Toxic chemicals

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Essentials of environmental toxicology: the effects of environmentally hazardous substances on human health

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This introductory text addresses the principles and mechanisms of toxicology as applied to environmentally-encountered toxic agents. Each chapter concludes with review questions that may be used for student self-testing and topics covered include dose response, hazards and risk assessment, determination of toxicity, pesticides, metals, plastics, organic solvents, environmental carcinogens, teratogens and mutagens Published Washington, D.C.; London: Taylor & Francis, 1996 This resource is available electronically from the following locations Copies on shelf at E-Resource.

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Examples of teratogens:
-Prescription and non-prescription drugs
-Illegal drugs
-Alcohol, tobacco and caffeine
-Infectious disease
-Maternal factors
K, Crowley. (2017) Child Development. London: SAGE

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https://youtu.be/jKnyEf81mo4
This gives some info about when different teratogens have more affect on the foetus

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Examples of Teratogens

There are many different examples of teratogens that cause birth defects. Listed in the directory below are some, for which we have provided a brief overview.

Fetal Alcohol Syndrome (FAS)

Phenytoin (Dilantin)

Varicella

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Teratogens are compounds and environmental conditions which interfere with normal in utero development.
J.G. Hall, Medical Epigenetics, 2016.

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Ways to reduce this is by taking less medication and exposure to:
Heat
Herbal Treatments
Ionizing Radiation
Children with runny noses and colds

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The extent of how a teratogen will affect a child depends on:
-Dose
-Heredity
-Age
-Combinations (pp 57-58)
K, Crowley. (2017) Child Development. London: SAGE
Teratogens are most dangerous and likely to cause more harm between weeks 2-12 off pregnancy, as this is when the foetus is forming vital organs.

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Some examples

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Harmful teratogens - Intro to Psychology

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Causes malformation of an embryo
examples could be drugs, medication, bacteria and viruses and certain health conditions

DOI: http://dx.doi.org/ 10.1055/s-0035-1556745

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useful website

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Good prenatal care is essential. The developing child is most at risk for some of the most severe problems during the first three months of development. Unfortunately, this is a time at which many mothers are unaware that they are pregnant. Today, we know many of the factors that can jeopardize the health of the developing child. The study of factors that contribute to birth defects is called teratology. Teratogens are environmental factors that can contribute to birth defects, and include some maternal diseases, pollutants, drugs and alcohol.

Factors influencing prenatal risks: There are several considerations in determining the type and amount of damage that might result from exposure to a particular teratogen (Berger, 2005). These include:

The timing of the exposure: Structures in the body are vulnerable to the most severe damage when they are forming. If a substance is introduced during a particular structure's critical period (time of development), the damage to that structure may be greater. For example, the ears and arms reach their critical periods at about 6 weeks after conception. If a mother exposes the embryo to certain substances during this period, the arms and ears may be malformed.

The amount of exposure: Some substances are not harmful unless the amounts reach a certain level. The critical level depends in part on the size and metabolism of the mother.

The number of teratogens: Fetuses exposed to multiple teratogens typically have more problems than those exposed to only one.

Genetics: Genetic make-up also plays a role on the impact a particular teratogen might have on the child. This is suggested by fraternal twins exposed to the same prenatal environment, but they do not experience the same teratogenic effects. The genetic make- up of the mother can also have an effect; some mothers may be more resistant to teratogenic effects than others.

Being male or female: Males are more likely to experience damage due to teratogens than are females. It is believed that the Y chromosome, which contains fewer genes than the X, may have an impact.

Figure 2.9 illustrates the timing of teratogen exposure and the types of structural defects that can occur during the prenatal period.

Alcohol: One of the most commonly used teratogens is alcohol, and because half of all pregnancies in the United States are unplanned, it is recommended that women of child-bearing age take great caution against drinking alcohol when not using birth control or when pregnant (CDC, 2005). Alcohol use during pregnancy is the leading preventable cause of intellectual disabilities in children in the United States (Maier & West, 2001). Alcohol consumption, particularly during the second month of prenatal development but at any point during pregnancy, may lead to neurocognitive and behavioral difficulties that can last a lifetime. Binge drinking (5 or more drinks on a single occasion) or 7 or more drinks during a single week place a child at risk.

In extreme cases, alcohol consumption during pregnancy can lead to fetal death, but also can result in Fetal Alcohol Spectrum Disorders (FASD), which is an umbrella term for the range of effects that can occur due to alcohol consumption during pregnancy (March of Dimes, 2016a). The most severe form of FASD is Fetal Alcohol Syndrome (FAS). Children with FAS share certain physical features such as flattened noses, small eye holes, and small heads (see Figure 2.10). Cognitively, these children have poor judgment, poor impulse control, higher rates of ADHD, learning issues, and lower IQ scores. These developmental problems and delays persist into adulthood (Streissguth, Barr, Kogan, & Bookstein, 1996) and can include criminal behavior, psychiatric problems, and unemployment (CDC, 2016a). Based on animal studies, it has been hypothesized that a mother's alcohol consumption during pregnancy may predispose her child to like alcohol (Youngentob, Molina, Spear, & Youngentob, 2007).

Head size

Below-average head circumference

Eyes

Smaller than average eye opening, skin folds at corners of eyes

Nose

Low nasal bridge, short nose

Midface

Smaller than average midface size

Lip and philtrum

Thin upper lip, indistinct philtrum

Figure 2.10 Fetal Alcohol Spectrum Disorders

Tobacco: Another widely used teratogen is tobacco. According to Tong et al. (2013) in conjunction with the Centers for Disease Control and Prevention, data from 27 sites in 2010 representing 52% of live births, showed that among women with recent live births:

About 23% reported smoking in the 3 months prior to pregnancy.

Almost 11% reported smoking during pregnancy.

More than half (54.3%) reported that they quit smoking by the last 3 months of pregnancy.

Almost 16% reported smoking after delivery.

When comparing the ages of women who smoked:

Women <20, 13.6% smoked during pregnancy

Women 20-24,17.6% smoked during pregnancy

Women 25-34, 8.8% smoked during pregnancy

Women ≥35, 5.7% smoked during pregnancy

The findings among racial and ethnic groups indicated that smoking during pregnancy was highest among American Indians/Alaska Natives (26.0%) and lowest among Asians/Pacific Islanders (2.1%).

When a pregnant woman smokes the fetus is exposed to dangerous chemicals including nicotine, carbon monoxide and tar, which lessen the amount of oxygen available to the fetus. Oxygen is important for overall growth and development. Tobacco use during pregnancy has been associated with low birth weight, ecotopic pregnancy ( fertilized egg implants itself outside of the uterus), placenta previa ( placenta lies low in the uterus and covers all or part of the cervix), placenta abruption ( placenta separates prematurely from the uterine wall), preterm delivery, stillbirth, fetal growth restriction, sudden infant death syndrome (SIDS), birth defects, learning disabilities, and early puberty in girls (Center for Disease Control, 2015d). A woman being exposed to second-hand smoke during pregnancy has also been linked to low-birth weight infants.

Prescription/Over-the-counter Drugs: About 70% of pregnant women take at least one prescription drug (March of Dimes, 2016e). A woman should not be taking any prescription drug during pregnancy unless it was prescribed by a health care provider who knows she is pregnant. Some prescription drugs can cause birth defects, problems in overall health, and development of the fetus. Over-the-counter drugs are also a concern during the prenatal period because they may cause certain health problems. For example, the pain reliever ibuprofen can cause serious blood flow problems to the fetus during the last three months.

Illicit Drugs: Common illicit drugs include cocaine, ecstasy and other club drugs, heroin, marijuana, and prescription drugs that are abused. It is difficult to completely determine the effects of a particular illicit drug on a developing child because most mothers who use, use more than one substance and have other unhealthy behaviors. These include smoking, drinking alcohol, not eating healthy meals, and being more likely to get a sexually transmitted disease. However, several problems seem clear. The use of cocaine is connected with low birth weight, stillbirths and spontaneous abortion. Heavy marijuana use is associated with problems in brain development (March of Dimes, 2016c). If a baby's mother used an addictive drug during pregnancy that baby can get addicted to the drug before birth and go through drug withdrawal after birth, also known as Neonatal Abstinence Syndrome (March of Dimes, 2015d). Other complications of illicit drug use include premature birth, smaller than normal head size, birth defects, heart defects, and infections. Additionally, babies born to mothers who use drugs may have problems later in life, including learning and behavior difficulties, slower than normal growth, and die from Sudden Infant Death Syndrome. Children of substance abusing parents are also considered at high risk for a range of biological, developmental, academic, and behavioral problems, including developing substance abuse problems of their own (Conners, et al., 2003).

Box 2.3 Should Women Who Use Drugs During Pregnancy Be Arrested and Jailed?

Women who use drugs or alcohol during pregnancy can cause serious lifelong harm to their child. Some people have advocated mandatory screenings for women who are pregnant and have a history of drug abuse, and if the women continue using, to arrest, prosecute, and incarcerate them (Figdor & Kaeser, 1998). This policy was tried in Charleston, South Carolina 20 years ago. The policy was called the Interagency Policy on Management of Substance Abuse During Pregnancy and had disastrous results.

The Interagency Policy applied to patients attending the obstetrics clinic at MUSC, which primarily serves patients who are indigent or on Medicaid. It did not apply to private obstetrical patients. The policy required patient education about the harmful effects of substance abuse during pregnancy. A statement also warned patients that protection of unborn and newborn children from the harms of illegal drug abuse could involve the Charleston police, the Solicitor of the Ninth Judicial Court, and the Protective Services Division of the Department of Social Services (DSS). (Jos, Marshall, & Perlmutter, 1995, pp. 120-121)

This policy seemed to deter women from seeking prenatal care, deterred them from seeking other social services, and was applied solely to low-income women, resulting in lawsuits. The program was canceled after 5 years, during which 42 women were arrested. A federal agency later determined that the program involved human experimentation without the approval and oversight of an institutional review board (IRB).

In July 2014, Tennessee enacted a law that allows women who illegally use a narcotic drug while pregnant to be prosecuted for assault if her infant is harmed or addicted to the drug (National Public Radio, 2015). According to the National Public Radio report, a baby is born dependent on a drug every 30 minutes in Tennessee, which is a rate three times higher than the national average. However, since the law took effect the number of babies born having drug withdrawal symptoms has not diminished. Critics contend that the criminal justice system should not be involved in what is considered a healthcare problem. What do you think? Is the issue of mothers using illicit drugs more of a legal or medical concern?

Pollutants: There are more than 83,000 chemicals used in the United States with little information on the effects of them during pregnancy (March of Dimes, 2016b). An environmental pollutant of significant concern is lead poisoning, which is connected with low birth weight and slowed neurological development. The chemicals in certain pesticides are also potentially damaging and may lead to birth defects, learning problems, low birth weight, miscarriage, and premature birth (March of Dimes, 2014). Prenatal exposure to bisphenol A (BPA), a chemical commonly used in plastics and food and beverage containers, may disrupt the action of certain genes contributing to certain birth defects (March of Dimes, 2016b). Radiation is another environmental hazard. If a mother is exposed to radiation, it can get into the bloodstream and pass through the umbilical cord to the baby. Radiation can also build up in body areas close to the uterus, such as the bladder. Exposure to radiation can slow the baby's growth, cause birth defects, affect brain development, cause cancer, and result in a miscarriage. Mercury, a heavy metal, can cause brain damage and affect the baby's hearing and vision. This is why women are cautioned about the amount and type of fish they consume during pregnancy.

Toxoplasmosis: The tiny parasite, toxoplasma gondii, causes an infection called Toxoplasmosis. According to the March of Dimes (2012d), toxoplasma gondii infects more than 60 million people in the United States. A healthy immune system can keep the parasite at bay producing no symptoms, so most people do not know they are infected. As routine prenatal screening frequently does not test for the presence of this parasite, pregnant women may want to talk to their health-care provider about being tested. Toxoplasmosis can cause premature birth, stillbirth, and can result in birth defects to the eyes and brain. While most babies born with this infection show no symptoms, ten percent may experience eye infections, enlarged liver and spleen, jaundice, and pneumonia. To avoid being infected, women should avoid eating undercooked or raw meat and unwashed fruits and vegetables, touching cooking utensils that touched raw meat or unwashed fruits and vegetables, and touching cat feces, soil or sand. If women think they may have been infected during pregnancy, they should have their baby tested.

Sexually Transmitted Diseases: Gonorrhea, syphilis, and chlamydia are sexually transmitted infections that can be passed to the fetus by an infected mother. Mothers should be tested as early as possible to minimize the risk of spreading these infections to their unborn child. Additionally, the earlier the treatment begins, the better the health outcomes for mother and baby (CDC, 2016d). Sexually transmitted diseases (STDs) can cause premature birth, premature rupture of the amniotic sac, an ectopic pregnancy, birth defects, miscarriage, and still births (March of Dimes, 2013). Most babies become infected with STDS while passing through the birth canal during delivery, but some STDs can cross the placenta and infect the developing fetus.

Human Immunodeficiency Virus (HIV): One of the most potentially devastating teratogens is HIV. HIV and Acquired Immune Deficiency Syndrome (AIDS) are leading causes of illness and death in the United States (Health Resources and Services Administration, 2015). One of the main ways children under age 13 become infected with HIV is via mother-to-child transmission of the virus prenatally, during labor, or by breastfeeding (CDC, 2016c). There are some measures that can be taken to lower the chance the child will contract the disease. HIV positive mothers who take antiviral medications during their pregnancy greatly reduce the chance of passing the virus to the fetus. The risk of transmission is less than 2 percent; in contrast, it is 25 percent if the mother does not take antiretroviral drugs (CDC, 2016b). However, the long-term risks of prenatal exposure to the medication are not known. It is recommended that women with HIV deliver the child by c-section, and that after birth they avoid breast feeding.

German measles (or rubella): Rubella, also called German measles, is an infection that causes mild flu-like symptoms and a rash on the skin. However, only about half of children infected have these symptoms, while others have no symptoms (March of Dimes, 2012a). Rubella has been associated with a number of birth defects. If the mother contracts the disease during the first three months of pregnancy, damage can occur in the eyes, ears, heart or brain of the unborn child. Deafness is almost certain if the mother has German measles before the 11th week of prenatal development and can also cause brain damage. Women in the United States are much less likely to be afflicted with rubella, because most women received childhood vaccinations that protect her from the disease.

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Good prenatal care is essential. The developing child is most at risk for some of the most severe problems during the first three months of development. Unfortunately, this is a time at which many mothers are unaware that they are pregnant. Today, we know many of the factors that can jeopardize the health of the developing child.

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The most common malformations include craniofacial dysmorphisms, cleft palate, thymic aplasia, and neural tube defects. The tranquilizer thalidomide is one of the most famous and notorious teratogens.

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Teratogen definition: "An environmental hazard to prenatal development" (pp. 523)

Reference: Gillibrand, R., Lam, V and L. O'Donnell, V (2011) Developmental Psychology. Essex: Pearson Education.

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A teratogen  is something that can cause or raise the risk for a birth defect in a baby. For example drugs, alcohol, certain medications and underlying health conditions.

This is a useful where i found my infomation.
https://www.nationwidechildrens.org/conditions/health-library/medical-genetics-teratogens

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Has a good description and background on Teratogens.

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Teratogens

Teratogens are substances that may produce physical or functional defects in the human embryo or fetus after the pregnant woman is exposed to the substance. Alcohol and cocaine are examples of such substances. Exposure to the teratogen affects the fetus or embryo in a variety of ways, such as the duration of exposure, the amount of teratogenic substance, and the stage of development the embryo or fetus is in during the exposure. Teratogens may affect the embryo or fetus in a number of ways, causing physical malformations, problems in the behavioral or emotional development of the child, and decreased intellectual quotient (IQ) in the child. Additionally, teratogens may also affect pregnancies and cause complications such as preterm labors, spontaneous abortions, or miscarriages. Teratogens are classified into four types: physical agents, metabolic conditions, infection, and finally, drugs and chemicals.

The word teratogen originates from the Greek word for monster, teratos. Isidore Geoffroy Saint-Hilaire, a physician from Paris, France, defined it in 1832 in Histoire générale et particuliére des anomalies de l'organisation chez l'homme et les animaux (General and Particular History of Structural Monstrosities in Man and Animals). People had sought explanations for abnormal human and animal development, however, for centuries, and they had developed different theories about the causes for the abnormalities. In Babylon, many said that infants with congenital malformations, or structural abnormalities present at birth, were constellations in human forms as well as fortune-tellers. Many early Hebrews said that abnormal development resulted from the deformed person's association with the devil. Aristotle, who lived in Athens, Greece in the fourth century, B.C., deemed birth defects as disturbances in reproduction rather than supernatural occurrences. Aristotle and Hippocrates, a physician who practiced in Greece in the fifth century B.C., claimed that a pregnant woman's experiences or emotions, which became called maternal impressions, can affect the formation of the fetus. The theory of maternal impressions persisted until the early 1900s, despite evidence to the contrary by John Hunter, a surgeon in Scotland in the late eighteenth century.

At the beginning of the 19th century, Johann Friedrich Meckel, the Younger, an anatomist from Halle, Germany, asserted that deviations from the normal developmental process caused malformations. Meckel wrote his doctoral thesis on an anatomical study of heart disease in 1802 and founded a journal dedicated to teratology, Journal für anatomische Varietäten, feinere und pathologische Anatomie ( Journal of Anatomical Varieties, Finer and Pathological Anatomy). Meckel examined anatomical defects and their causes. Because he asserted that to understand abnormal development, one must first understand normal development, he documented his observations of normal embryological development of mammals in a sequence of forms. Meckel also categorized abnormal development into four basic types: reduced or absent body parts (insufficient generative energy), enlarged or multiple body parts (excessive energy), aberration of form and of position, and hermaphroditism, which included deformities such as ambiguous genitalia.

Following Meckel, scientists in the nineteenth century began experimental studies to detect teratogens. Etienne Geoffroy Saint-Hilaire in Paris, France, experimented on chick eggs by subjecting them to pricking, inversion, jarring, and abnormally high or low temperatures to study the resulting malformations; he believed that certain manipulations could invoke specific deformations. Although deformities materialized, Saint-Hilaire didn't identify their exact causes. His son Isidore then reported the results of the experiments between the years of 1832 and 1837 in his three-volume Traité de Tératologie (Treatise on Teratology). Other scientists following Saint-Hilaire also experimented with teratogens, notably Camille Dareste in France, who successfully produced abnormalities in chick embryos during twenty-two years of experiments until his death in 1899.

Scientists in the twentieth century classified teratogens into four categories, physical, chemical, or infectious agents and maternal conditions. Physical agents include ionizing radiation or other agents that contribute to hyperthermia, or elevated body temperature. Ionizing radiation is radiation composed of particles, X-rays, or gamma rays that carry adequate energy to free an electron from an atom or molecule, resulting in electrically charged ions in matter. In the 1920s reports surfaced of abnormalities in the children of women who were X-rayed while pregnant. The common anomalies were small head circumference, or microcephaly, and small eyes, or microphthalmia. Douglas P. Murphy, from the University of Pennsylvania in Philadelphia, Pennsylvania, surveyed gynecologists and radiologists across the US between 1928 and 1929, and found that of the seventy-four children reported to have been exposed to radiation in utero, twenty-five were malformed.

Agents that cause hyperthermia are also physical teratogens. These could be saunas, hot tubs, or infections that raise a pregnant woman's body temperature to 102 degrees Fahrenheit or higher. Scientists have shown that hyperthermia-causing agents acted as teratogens in both animals and humans. Experiments on animals, such as guinea pigs, hamsters, rats, mice, rabbits, sheep, pigs, and monkeys from the early 1970s to the early 1990s demonstrated that hyperthermia causes central nervous system malformations, microcephaly, abdominal wall defects, defects of the eye and palate, and limb reduction defects. David L. Cockroft and Denis Alan Trevor New in the UK reported in the 1970s that heating explanted rat embryos caused microcephaly, enlarged hearts, and skeletal deformities. In the 1980s, scientists used other agents to cause hyperthermia in pregnant females, such as ultrasound and electromagnetic radiation, to test the agent's capacity to cause birth defects in offspring. In humans, hyperthermia is associated with neural tube defects, spontaneous abortions, and various cardiovascular abnormalities. Physicians and scientists gathered evidence in the early 1990s which supported their theories that there was an association between the high fevers of pregnant women and congenital abnormalities, such as cardiac defects, abdominal wall defects, or a disruption of the enervation of the large intestine called Hirschsprung disease, in their offspring.

Metabolic conditions affecting pregnant females such as malnutrition, diabetes, and thyroid disorders are a second category of teratogens. Metabolic conditions are abnormalities in the chemical process of producing energy from food, and thereby affect the development and function of the body. If a pregnant woman is malnourished, then her fetus likely lacks the nutrients essential for its development. In the case of diabetes, low blood sugar, or hypoglycemia, may cause fetal malformations. Hypoglycemia interferes with some proteins in the developing fetal heart by increasing the expression of proteins which are regulated by glucose. Excessive blood sugar, also seen with diabetes, may cause neural tube defects, or birth defects of the brain and spinal cord, and may also induce the release of free radicals, or damaged cells that are missing an essential molecule, which disrupt fetal development. In the 2000s, The Society of Obstetricians and Gynaecologists of Canada reviewed reports from 1990 to 2005 on the risk of congenital anomalies in pregnancies caused by pre-existing or gestational diabetes. They found that the risk of major malformations increases from four to ten percent in infants of diabetic mothers. This statistic was two to three times higher than that in general populations.

Thyroid disorders include disorders in which the thyroid gland malfunctions, thereby producing abnormal amounts of the thyroid hormones, thyroxine and triiodothyronine, which regulate metabolism. Thyroid disorders can cause a number of teratogenic effects to a developing fetus, as well as adverse effects on pregnancy such as miscarriage, premature separation of the placenta from the uterine wall (placental abruption), preterm labor, and lower IQ scores in the children. In the 1940s, pediatrician Josef Warkany and colleagues in Cincinnati, Ohio raised female rats on a diet high in substances which interfere with thyroid function or goitrogens. As a result of this diet, the pregnant females developed enlarged thyroid glands and their offspring had skeletal malformations such as abnormally short jaw bones and tails, shortened or absent lower leg bones, and fusion of the ribs.

Infections such as those caused by rubella virus, herpes simplex virus, and syphilis, are a third kind of teratogen. In 1941, ophthalmologist Norman McAlister Gregg at the Royal Alexandra Hospital for Children in Sydney, Australia witnessed cataracts in seventy-eight children whose mothers were infected with the rubella virus during either the first or second months of pregnancy. The connection Gregg made between the virus and congenital malformations contributed to one of the first discoveries of a teratogen that wasn't a manufactured chemical. In addition to rubella, herpes simplex virus, and cytomegalovirus-one of the herpes viruses that passes through direct contact with body fluids, congenital abnormalities can be caused by infections of Toxoplasma gondii, a parasite often obtained by eating contaminated meat, drinking contaminated water, or coming into contact with infected cat feces, and Treponema pallidum, the bacterium that causes syphilis.

The fourth kind of teratogen includes drugs and chemicals the pregnant female ingests such as alcohol, cocaine, thalidomide, Agent Orange, and vitamin A and its derivatives, called retionids. In 1933, Fred Hale at the Texas Agricultural Experiment Station in College Station, Texas, fed pregnant female pigs a diet severely deficient in vitamin A and found that the offspring had various congenital malformations such as anophthalmia, which is the absence of one or both eyes, and cleft palate. Over the next four years, Hale experimented with pigs and vitamin A deficiency and found other defects such as cleft lip and malformed hind legs. Hale's experiments established that an absence or deficiency of a nutrient could produce severe congenital malformations in mammalian embryos. In 1953, pediatrician Sidney Q. Cohlan in New York City, New York, reported that large doses of vitamin A caused congenital malformations of the central nervous system and other systems in rats. That announcement led to decades of experimentation with vitamin A and its derivatives, retinoids.

In the 1960s, thalidomide provided one of the first instances when governments enacted regulations regarding the risk of teratogens to the developing fetus. Thalidomide had been patented in 1954 and was approved for use in Europe as a sedative and anti-nausea medicine for pregnant women. After several years on the market, physicians noted that women who had taken thalidomide while pregnant gave birth to a increased number of infants with severe malformations such as shortened, absent, or extra limbs (dysmelia), incomplete development or a below average number of cells (bone hypoplasticity), and a variety of ear, heart, and internal organ defects. In 1961, physician Widukind Lenz in Hamburg, Germany reported his observations on thalidomide's teratogenicity and the drug was soon taken off the market. Physician and pharmacologist Frances Kelsey of the US Food and Drug Administration (FDA), headquartered in Washington D.C., never approved the sale of thalidomide in the US. Kelsey requested more clinical test results after she received reports of the adverse effects of thalidomide in Europe. Approximately 10,000 babies worldwide were born with defects due to thalidomide. After the thalidomide incident, in August 1962, the American Pharmaceutical Manufacturers Association implored the US pharmaceutical industry to establish a Commission on Drug Safety to develop ways of improving animal teratogenicity tests. In 1966, the FDA issued Guidelines for Reproductive Studies for Safety Evaluation of Drugs for Human Use, which created a standard for evaluating teratogenicity and was issued in many countries.

In 1977, James G. Wilson at the University of Florida Medical School in Gainesville, Florida, refined the principles of teratology he had first introduced in 1959 at a conference on congenital malformations. Wilson's six principles of teratology state verbatim:

1. Sensitivity to teratogen-induced malformation depends on the genotype (species) of the conceptus.

2. Sensitivity to teratogen-induced malformation varies during different developmental stages at the time of exposure, where there are critical periods of sensitivity to agents and organ systems.

3. Teratogens act via a specific mechanism on developing cells and tissues to initiate a cascade of altered developmental events.

4. Teratogenic effects are dependent on the nature of the teratogen, including chemical properties of the chemical, route of exposure, maternal/fetal bioactivation, placental transport, etc.

5. Teratogens produce a consistent deviation from normal development. Deviation can include: (1) death, (2) malformation, (3) growth retardation, or (4) functional defect.

6. Teratogen-induced malformations occur in a dose-dependent manner, ranging from no observable defects to total lethality.

Alcohol, which also falls under the fourth category of teratogen, can cause Fetal Alcohol Syndrome (FAS) in children born to women who drank too much alcohol while pregnant. FAS can cause defects such as minor facial abnormalities and damage to the brain, which consequently leads to learning, behavioral, and cognitive abnormalities. In the US, pediatricians David W. Smith and Kenneth L. Jones examined a group of children at the University of Washington's Harborview Medical Center in Seattle, Washington in 1973. Of the eight children observed, four had similar deficiencies in growth and cognitive development. This observation led Smith and Jones to investigate alcohol as a teratogen and over the next few years, the duo collected case studies of children born to alcoholic mothers to enumerate morphological anomalies and growth deficiencies associated with FAS.

Today, the FDA monitors teratogen exposures to pregnant women in the US with a number of regulations and risk management programs. For example, the retinoic acid isotretinoin which is commonly used for acne treatment cannot be given to any patient unless they are enrolled in iPLEDGE, a risk management program designed to prevent fetal exposure to isotretinoin.

Sources

1. Allen, Victoria M., and B. Anthony Armson. "Teratogenicity Associated with Pre-Existing and Gestational Diabetes." Journal of Obstetrics and Gynaecology Canada 200 (2007): 927-934.http://www.jogc.com/abstracts/full/200711_SOGCClinicalPracticeGuidelines_1.pdf (Accessed January 9, 2014).

2. Angles, J.M., D.A. Walsh, K. Li, S.B. Barnett, and Marshall J. Edwards. "Effects of Pulsed Ultrasound and Temperature on the Development of Rat Embryos in Culture." Teratology 42 (1990): 285-93.

3. Barrow, Mark V. "A Brief History of Teratology to the Early 20th Century." Teratology 4 (1971): 119-29.

4. Brown-Woodman, Patricia D. C., John A. Hadley, Janet Waterhose, and William S. Webster. "Teratogenic Effects of Exposure to Radiofrequency Radiation (27.12 MHz) from a Shortwave Diathermy Unit." Toxicology and Industrial Health 26 (1988): 1-10.

5. Centers for Disease Control and Prevention. "Cytomegalovirus (CMV) and Congenital CMV Infection." USA.gov. http://www.cdc.gov/cmv/index.html (Accessed October 15, 2012).

6. Centers for Disease Control and Prevention. "Parasites-Toxoplasmosis (Toxoplasma Infection)." USA.gov. http://www.cdc.gov/parasites/toxoplasmosis/ (Accessed October 15, 2012).

7. Chambers, Christina D., Kathleen A. Johnson, Robert J. Felix, Lyn M. Dick, and Kenneth Lyons Jones. "Hyperthermia in Pregnancy: A Prospective Cohort Study." Teratology 55 (1997): 45.

8. Children's Hospital of Wisconsin. "Teratogens." Children's Hospital and Health System. http://www.chw.org/display/PPF/DocID/22924/router.asp (Accessed June 14, 2012).

9. Clark, Owen E. "The Contributions of J.F. Meckel, the Younger, to the Science of Teratology." Journal of the History of Medicine and Allied Sciences 24 (1969): 310-22.

10. Cockroft, David L., and Denis Alan Trevor New. "Effects of Hyperthermia on Rat Embryos in Culture." Nature 258 (1975): 604-6.

11. Cockroft, David L., and Denis Alan Trevor New. "Abnormalities Induced in Cultured Rat Embryos by Hyperthermia." Teratology 17 (1978): 277-84.

12. Cohlan, Sidney Q. "Excessive Intake of Vitamin A as a Cause of Congenital Anomalies in the Rat." Science 117 (1953): 535-6.

13. Dareste, Camille. Recherches sur la production artificielle des monstruosités, ou, Essais de tératogénie expérimentale [Research on the production of artificial monstrosities, or, Essays on experimental teratology]. Paris: E. Reinwald, 1877 http://dx.doi.org/10.5962/bhl.title.45945 (Accessed January 8, 2014).

14. Edwards, Marshall J. "Hyperthermia as a Teratogen: A Review of Experimental Studies and Their Clinical Significance." Teratogenesis, Carcinogenesis, and Mutagenesis 6 (1986): 563-82.

15. Finnell, Richard H. "Teratology: General Consideration and Principles." Journal of Allergy and Clinical Immunology 103 (1999): 337-42.

16. Friedman, Jan M. "The Principles of Teratology: Are They Still True?" Birth Defects Research Part A: Clinical and Molecular Teratology 88 (2010): 766-8.

17. Garfield, Eugene. "Teratology Literature and the Thalidomide Controversy." In Essays of an Information Scientist. Philadelphia: ISI Press, 1986, 404-12.

18. Germain, Mary-Ann, William S. Webster, and Marshall J. Edwards. "Hyperthermia as a Teratogen: Parameters Determining Hyperthermia-Induced Head Defects in the Rat." Teratology 31 (1985): 265-72.

19. Goldstein, Leopold and Douglas P. Murphy. "Microcephalic Idiocy Following Radium Therapy for Uterine Cancer During Pregnancy." American Journal of Obstetrics and Gynecology 18 (1929): 89-95.

20. Graham Jr., John M., and Marshall J. Edwards. "Teratogenic Effects of Maternal Hyperthermia." Annals of the Research Institute of Environmental Medicine 40 (1989): 365-74.

21. Graham Jr., John M., Matthew J. Edwards, and Marshall J. Edwards. "Teratogen Update: Gestational Effects of Maternal Hyperthermia Due to Febrile Illnesses and Resultant Patterns of Defects in Humans." Teratology 58 (1998): 209-21.

22. Gregg, Norman McAlister. "Congenital Cataract Following German Measles in the Mother." Transactions of the Ophthalmological Society of Australia 3 (1941): 35-46. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2272051/ (Accessed January 8, 2014).

23. Hale, Fred. "Pigs Born Without Eyeballs." Journal of Heredity 24 (1933): 105-6. http://www.oxfordjournals.org/our_journals/jhered/freepdf/24-105.pdf (Accessed January 8, 2014).

24. Hellmann, Wilhelmine. "Endotoxin Fever and Anomalies of Development in Rabbits." Arzneimittel-Forschung 29 (1977): 1062-4.

25. Hill, Robert. "Model Systems and Their Predictive Value in Assessing Teratogens." Fundamental and Applied Toxicology 3 (1983): 229-32.

26. Kalter, Harold. "Teratology in the 20th Century: Environmental Causes of Congenital Malformations in Humans and How They Were Established." Neurotoxicology and Teratology 25 (2003): 131-282.

27. Lary, Joseph M., David L. Conover, Edward D. Foley, and Peggy L. Hanser. "Teratogenic Effects of 27.12 MHz Radiofrequency in Rats." Teratology 26 (1982): 299-309.

28. Lary, Joseph M., David L. Conover, Peggy H. Johnson, and Jenné A. Burg. "Teratogenicity of 27.12-MHz Radiation in Rats is Related to Duration of Hyperthermic Exposure." Bioelectromagnetics 4 (1983): 249-55.

29. Lenz, Widukind and Klais Knapp. "Thalidomide embryopathy." Archives of Environmental Health: An International Journal 5 (1962): 14-19.

30. Lipson, Anthony, John M. Optiz, and James F. Reynolds. "Hirschsprung Disease in the Offspring of Mothers Exposed to Hyperthermia During Pregnancy." American Journal of Medical Genetics 29 (1988): 117-24.

31. Little, Bertis B., Fred E. Ghali, Laura M. Snell, Kraig A. Knoll, W. Johnston, and Larry C. Gilstrap "Is Hyperthermia Teratogenic in the Human?" American Journal of Perinatology 8 (1991): 185-9.

32. Meyers, Vera Kolb. "Chemicals Which Cause Birth Defects-Teratogens: A Special Concern of Research Chemists." Science of the Total Environment 32 (1983): 1-12.

33. Murphy, Douglas P. "Ovarian Irradiation; Its Effects on the Health of Subsequent Children: Review of the Literature, Experimental and Clinical, with a Report of Three-Hundred and Twenty Human Pregnancies." Surgery, Gynecology, and Obstetrics 47 (1928): 201-5.

34. Murphy, Douglas P. "Outcome of 625 Pregnancies in Women Subjected to Pelvic Radium or Roentgen Irradiation." American Journal of Obstetrics and Gynecology 18 (1929): 79

35. Ringholm, Lene, Ulrik Pedersen-Bjergaard, Birger Thorsteinsson, Peter Damm, and Elisabeth R. Mathiesen. "Hypoglycaemia During Pregnancy in Women with Type 1 Diabetes." Diabetic Medicine 29 (2012): 558-66.

36. Saint-Hilaire, Isidore Geoffroy. 1832-1837. Histoire générale et particuliére des anomalies de l'organisation chez l'homme et les animaux, ouvrage comprenant des rescherches sur les caractéres, la classification, l'influence physiologique et pathologique, les rapports généraux, les lois et les causes des monstruosités, des variétés et vices de conformation, ou traité de tératogologie (General and particular history of the abnormalities of the organization of humans and animals, or work comprising researches on characters, classification, physiological and pathological influence, general relations, the laws and causes of monstrosities, varieties and vices in formation, or treatise on teratology). 3 Vols. and atlas. Paris: Balliere, 1832-1837. http://dx.doi.org/10.5962/bhl.title.50400 (Accessed January 8, 2014).

37. Smoak, Ida W. "Hypoglycemia and Embryonic Heart Development." Frontiers in Bioscience 7 (2002): 307-18.

38. Squier, Susan. Poultry Science, Chicken Culture. Piscataway, NJ: Rutgers University Press, 2011.

39. US Department of Health, Education and Welfare, Food and Drug Administration Bulletin. Guidelines for Reproductive Studies for Safety Evaluation of Drugs for Human Use. January 1966.

40. Vissenberg, Rosa, Emmy van den Boogaard, Madelon van Wely, Joris A. van der Post, Eric Fliers, Peter H. Bisschop, and Mariëtte Goddijn. "Treatment of Thyroid Disorders Before Conception and in Early Pregnancy: A Systematic Review." Human Reproduction Update 18 (2012): 360-73.

41. Warkany, Josef and Rose C. Nelson. "Changes in the Anterior Pituitary Gland of Rats with Experimental Goiter." Proceedings of the Society for Experimental Biology and Medicine 39 (1938) 66-71.

42. Warkany, Josef and Rose C. Nelson. "Appearance of Skeletal Abnormalities in the Offspring of Rats Reared on a Deficient Diet." Science 92 (1940): 383-4.

43. Warkany, Josef and Rose C. Nelson. "Skeletal Abnormalities in the Offspring of Rats Reared on Deficient Diets." The Anatomical Record 79 (1941): 83-100.

44. Warkany, Josef, Rose C. Nelson, and Elizabeth Scraffenberger. "Congenital Malformations Induced in Rats by Maternal Nutritional Deficiency: II. Use of Varied Diets and of Different Strains of Rat." American Journal of Diseases of Children 64 (1942): 860-6.

45. Warkany, Josef and Rose C. Nelson. "Congenital Malformations Induced in rats by Maternal Nutritional Deficiency." Journal of Nutrition 23 (1942): 321-33. http://jn.nutrition.org/content/23/4/321.full.pdf+html(Accessed January 8, 2014).

46. Wilson, James G. Environment and Birth Defects. New York, New York: Academic Press, 1973.

47. Wilson, James G. "Current Status of Teratology: General Principles and Mechanisms Derived from Animal Studies." In Handbook of Teratology, eds. James G. Wilson and Frank Clarke Fraser, Vol. 1. New York: Plenum Press, 1977, 47-74.

48. Wilson, James G. "The Evolution of Teratological Testing." Teratology 20 (1979): 205-11.

49. Zuck, Michael V. "Teratogen." In The Gale Encyclopedia of Genetic Disorders, Vol. 2, 2nd ed., ed. Brigham Narins. Detroit: Gale, 2006, 1246-8.

Tantibanchachai, Chanapa, "Teratogens". Embryo Project Encyclopedia (2014-01-22). ISSN: 1940-5030 http://embryo.asu.edu/handle/10776/7510.

Arizona State University. School of Life Sciences. Center for Biology and Society. Embryo Project Encyclopedia.

Copyright Arizona Board of Regents Licensed as Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported (CC BY-NC-SA 3.0) http://creativecommons.org/licenses/by-nc-sa/3.0/

Teratogens; Abnormalities, Human; Fetus; Pregnancy; Teratogenicity testing; Embryos; Teratogenic agents; Human embryo; Fetus; Miscarriage; Thalidomide; Concept

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Teratogens Teratogens are substances that may produce physical or functional defects in the human embryo or fetus after the pregnant woman is exposed to the substance. Alcohol and cocaine are examples of such substances.

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This is a useful page for info on what teratogens are and the effect they have

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Teratogens

Teratogens are substances that may produce physical or functional defects in the human embryo or fetus after the pregnant woman is exposed to the substance. Alcohol and cocaine are examples of such substances. Exposure to the teratogen affects the fetus or embryo in a variety of ways, such as the duration of exposure, the amount of teratogenic substance, and the stage of development the embryo or fetus is in during the exposure. Teratogens may affect the embryo or fetus in a number of ways, causing physical malformations, problems in the behavioral or emotional development of the child, and decreased intellectual quotient (IQ) in the child. Additionally, teratogens may also affect pregnancies and cause complications such as preterm labors, spontaneous abortions, or miscarriages. Teratogens are classified into four types: physical agents, metabolic conditions, infection, and finally, drugs and chemicals.

The word teratogen originates from the Greek word for monster, teratos. Isidore Geoffroy Saint-Hilaire, a physician from Paris, France, defined it in 1832 in Histoire générale et particuliére des anomalies de l'organisation chez l'homme et les animaux (General and Particular History of Structural Monstrosities in Man and Animals). People had sought explanations for abnormal human and animal development, however, for centuries, and they had developed different theories about the causes for the abnormalities. In Babylon, many said that infants with congenital malformations, or structural abnormalities present at birth, were constellations in human forms as well as fortune-tellers. Many early Hebrews said that abnormal development resulted from the deformed person's association with the devil. Aristotle, who lived in Athens, Greece in the fourth century, B.C., deemed birth defects as disturbances in reproduction rather than supernatural occurrences. Aristotle and Hippocrates, a physician who practiced in Greece in the fifth century B.C., claimed that a pregnant woman's experiences or emotions, which became called maternal impressions, can affect the formation of the fetus. The theory of maternal impressions persisted until the early 1900s, despite evidence to the contrary by John Hunter, a surgeon in Scotland in the late eighteenth century.

At the beginning of the 19th century, Johann Friedrich Meckel, the Younger, an anatomist from Halle, Germany, asserted that deviations from the normal developmental process caused malformations. Meckel wrote his doctoral thesis on an anatomical study of heart disease in 1802 and founded a journal dedicated to teratology, Journal für anatomische Varietäten, feinere und pathologische Anatomie ( Journal of Anatomical Varieties, Finer and Pathological Anatomy). Meckel examined anatomical defects and their causes. Because he asserted that to understand abnormal development, one must first understand normal development, he documented his observations of normal embryological development of mammals in a sequence of forms. Meckel also categorized abnormal development into four basic types: reduced or absent body parts (insufficient generative energy), enlarged or multiple body parts (excessive energy), aberration of form and of position, and hermaphroditism, which included deformities such as ambiguous genitalia.

Following Meckel, scientists in the nineteenth century began experimental studies to detect teratogens. Etienne Geoffroy Saint-Hilaire in Paris, France, experimented on chick eggs by subjecting them to pricking, inversion, jarring, and abnormally high or low temperatures to study the resulting malformations; he believed that certain manipulations could invoke specific deformations. Although deformities materialized, Saint-Hilaire didn't identify their exact causes. His son Isidore then reported the results of the experiments between the years of 1832 and 1837 in his three-volume Traité de Tératologie (Treatise on Teratology). Other scientists following Saint-Hilaire also experimented with teratogens, notably Camille Dareste in France, who successfully produced abnormalities in chick embryos during twenty-two years of experiments until his death in 1899.

Scientists in the twentieth century classified teratogens into four categories, physical, chemical, or infectious agents and maternal conditions. Physical agents include ionizing radiation or other agents that contribute to hyperthermia, or elevated body temperature. Ionizing radiation is radiation composed of particles, X-rays, or gamma rays that carry adequate energy to free an electron from an atom or molecule, resulting in electrically charged ions in matter. In the 1920s reports surfaced of abnormalities in the children of women who were X-rayed while pregnant. The common anomalies were small head circumference, or microcephaly, and small eyes, or microphthalmia. Douglas P. Murphy, from the University of Pennsylvania in Philadelphia, Pennsylvania, surveyed gynecologists and radiologists across the US between 1928 and 1929, and found that of the seventy-four children reported to have been exposed to radiation in utero, twenty-five were malformed.

Agents that cause hyperthermia are also physical teratogens. These could be saunas, hot tubs, or infections that raise a pregnant woman's body temperature to 102 degrees Fahrenheit or higher. Scientists have shown that hyperthermia-causing agents acted as teratogens in both animals and humans. Experiments on animals, such as guinea pigs, hamsters, rats, mice, rabbits, sheep, pigs, and monkeys from the early 1970s to the early 1990s demonstrated that hyperthermia causes central nervous system malformations, microcephaly, abdominal wall defects, defects of the eye and palate, and limb reduction defects. David L. Cockroft and Denis Alan Trevor New in the UK reported in the 1970s that heating explanted rat embryos caused microcephaly, enlarged hearts, and skeletal deformities. In the 1980s, scientists used other agents to cause hyperthermia in pregnant females, such as ultrasound and electromagnetic radiation, to test the agent's capacity to cause birth defects in offspring. In humans, hyperthermia is associated with neural tube defects, spontaneous abortions, and various cardiovascular abnormalities. Physicians and scientists gathered evidence in the early 1990s which supported their theories that there was an association between the high fevers of pregnant women and congenital abnormalities, such as cardiac defects, abdominal wall defects, or a disruption of the enervation of the large intestine called Hirschsprung disease, in their offspring.

Metabolic conditions affecting pregnant females such as malnutrition, diabetes, and thyroid disorders are a second category of teratogens. Metabolic conditions are abnormalities in the chemical process of producing energy from food, and thereby affect the development and function of the body. If a pregnant woman is malnourished, then her fetus likely lacks the nutrients essential for its development. In the case of diabetes, low blood sugar, or hypoglycemia, may cause fetal malformations. Hypoglycemia interferes with some proteins in the developing fetal heart by increasing the expression of proteins which are regulated by glucose. Excessive blood sugar, also seen with diabetes, may cause neural tube defects, or birth defects of the brain and spinal cord, and may also induce the release of free radicals, or damaged cells that are missing an essential molecule, which disrupt fetal development. In the 2000s, The Society of Obstetricians and Gynaecologists of Canada reviewed reports from 1990 to 2005 on the risk of congenital anomalies in pregnancies caused by pre-existing or gestational diabetes. They found that the risk of major malformations increases from four to ten percent in infants of diabetic mothers. This statistic was two to three times higher than that in general populations.

Thyroid disorders include disorders in which the thyroid gland malfunctions, thereby producing abnormal amounts of the thyroid hormones, thyroxine and triiodothyronine, which regulate metabolism. Thyroid disorders can cause a number of teratogenic effects to a developing fetus, as well as adverse effects on pregnancy such as miscarriage, premature separation of the placenta from the uterine wall (placental abruption), preterm labor, and lower IQ scores in the children. In the 1940s, pediatrician Josef Warkany and colleagues in Cincinnati, Ohio raised female rats on a diet high in substances which interfere with thyroid function or goitrogens. As a result of this diet, the pregnant females developed enlarged thyroid glands and their offspring had skeletal malformations such as abnormally short jaw bones and tails, shortened or absent lower leg bones, and fusion of the ribs.

Infections such as those caused by rubella virus, herpes simplex virus, and syphilis, are a third kind of teratogen. In 1941, ophthalmologist Norman McAlister Gregg at the Royal Alexandra Hospital for Children in Sydney, Australia witnessed cataracts in seventy-eight children whose mothers were infected with the rubella virus during either the first or second months of pregnancy. The connection Gregg made between the virus and congenital malformations contributed to one of the first discoveries of a teratogen that wasn't a manufactured chemical. In addition to rubella, herpes simplex virus, and cytomegalovirus-one of the herpes viruses that passes through direct contact with body fluids, congenital abnormalities can be caused by infections of Toxoplasma gondii, a parasite often obtained by eating contaminated meat, drinking contaminated water, or coming into contact with infected cat feces, and Treponema pallidum, the bacterium that causes syphilis.

The fourth kind of teratogen includes drugs and chemicals the pregnant female ingests such as alcohol, cocaine, thalidomide, Agent Orange, and vitamin A and its derivatives, called retionids. In 1933, Fred Hale at the Texas Agricultural Experiment Station in College Station, Texas, fed pregnant female pigs a diet severely deficient in vitamin A and found that the offspring had various congenital malformations such as anophthalmia, which is the absence of one or both eyes, and cleft palate. Over the next four years, Hale experimented with pigs and vitamin A deficiency and found other defects such as cleft lip and malformed hind legs. Hale's experiments established that an absence or deficiency of a nutrient could produce severe congenital malformations in mammalian embryos. In 1953, pediatrician Sidney Q. Cohlan in New York City, New York, reported that large doses of vitamin A caused congenital malformations of the central nervous system and other systems in rats. That announcement led to decades of experimentation with vitamin A and its derivatives, retinoids.

In the 1960s, thalidomide provided one of the first instances when governments enacted regulations regarding the risk of teratogens to the developing fetus. Thalidomide had been patented in 1954 and was approved for use in Europe as a sedative and anti-nausea medicine for pregnant women. After several years on the market, physicians noted that women who had taken thalidomide while pregnant gave birth to a increased number of infants with severe malformations such as shortened, absent, or extra limbs (dysmelia), incomplete development or a below average number of cells (bone hypoplasticity), and a variety of ear, heart, and internal organ defects. In 1961, physician Widukind Lenz in Hamburg, Germany reported his observations on thalidomide's teratogenicity and the drug was soon taken off the market. Physician and pharmacologist Frances Kelsey of the US Food and Drug Administration (FDA), headquartered in Washington D.C., never approved the sale of thalidomide in the US. Kelsey requested more clinical test results after she received reports of the adverse effects of thalidomide in Europe. Approximately 10,000 babies worldwide were born with defects due to thalidomide. After the thalidomide incident, in August 1962, the American Pharmaceutical Manufacturers Association implored the US pharmaceutical industry to establish a Commission on Drug Safety to develop ways of improving animal teratogenicity tests. In 1966, the FDA issued Guidelines for Reproductive Studies for Safety Evaluation of Drugs for Human Use, which created a standard for evaluating teratogenicity and was issued in many countries.

In 1977, James G. Wilson at the University of Florida Medical School in Gainesville, Florida, refined the principles of teratology he had first introduced in 1959 at a conference on congenital malformations. Wilson's six principles of teratology state verbatim:

1. Sensitivity to teratogen-induced malformation depends on the genotype (species) of the conceptus.

2. Sensitivity to teratogen-induced malformation varies during different developmental stages at the time of exposure, where there are critical periods of sensitivity to agents and organ systems.

3. Teratogens act via a specific mechanism on developing cells and tissues to initiate a cascade of altered developmental events.

4. Teratogenic effects are dependent on the nature of the teratogen, including chemical properties of the chemical, route of exposure, maternal/fetal bioactivation, placental transport, etc.

5. Teratogens produce a consistent deviation from normal development. Deviation can include: (1) death, (2) malformation, (3) growth retardation, or (4) functional defect.

6. Teratogen-induced malformations occur in a dose-dependent manner, ranging from no observable defects to total lethality.

Alcohol, which also falls under the fourth category of teratogen, can cause Fetal Alcohol Syndrome (FAS) in children born to women who drank too much alcohol while pregnant. FAS can cause defects such as minor facial abnormalities and damage to the brain, which consequently leads to learning, behavioral, and cognitive abnormalities. In the US, pediatricians David W. Smith and Kenneth L. Jones examined a group of children at the University of Washington's Harborview Medical Center in Seattle, Washington in 1973. Of the eight children observed, four had similar deficiencies in growth and cognitive development. This observation led Smith and Jones to investigate alcohol as a teratogen and over the next few years, the duo collected case studies of children born to alcoholic mothers to enumerate morphological anomalies and growth deficiencies associated with FAS.

Today, the FDA monitors teratogen exposures to pregnant women in the US with a number of regulations and risk management programs. For example, the retinoic acid isotretinoin which is commonly used for acne treatment cannot be given to any patient unless they are enrolled in iPLEDGE, a risk management program designed to prevent fetal exposure to isotretinoin.

Sources

1. Allen, Victoria M., and B. Anthony Armson. "Teratogenicity Associated with Pre-Existing and Gestational Diabetes." Journal of Obstetrics and Gynaecology Canada 200 (2007): 927-934.http://www.jogc.com/abstracts/full/200711_SOGCClinicalPracticeGuidelines_1.pdf (Accessed January 9, 2014).

2. Angles, J.M., D.A. Walsh, K. Li, S.B. Barnett, and Marshall J. Edwards. "Effects of Pulsed Ultrasound and Temperature on the Development of Rat Embryos in Culture." Teratology 42 (1990): 285-93.

3. Barrow, Mark V. "A Brief History of Teratology to the Early 20th Century." Teratology 4 (1971): 119-29.

4. Brown-Woodman, Patricia D. C., John A. Hadley, Janet Waterhose, and William S. Webster. "Teratogenic Effects of Exposure to Radiofrequency Radiation (27.12 MHz) from a Shortwave Diathermy Unit." Toxicology and Industrial Health 26 (1988): 1-10.

5. Centers for Disease Control and Prevention. "Cytomegalovirus (CMV) and Congenital CMV Infection." USA.gov. http://www.cdc.gov/cmv/index.html (Accessed October 15, 2012).

6. Centers for Disease Control and Prevention. "Parasites-Toxoplasmosis (Toxoplasma Infection)." USA.gov. http://www.cdc.gov/parasites/toxoplasmosis/ (Accessed October 15, 2012).

7. Chambers, Christina D., Kathleen A. Johnson, Robert J. Felix, Lyn M. Dick, and Kenneth Lyons Jones. "Hyperthermia in Pregnancy: A Prospective Cohort Study." Teratology 55 (1997): 45.

8. Children's Hospital of Wisconsin. "Teratogens." Children's Hospital and Health System. http://www.chw.org/display/PPF/DocID/22924/router.asp (Accessed June 14, 2012).

9. Clark, Owen E. "The Contributions of J.F. Meckel, the Younger, to the Science of Teratology." Journal of the History of Medicine and Allied Sciences 24 (1969): 310-22.

10. Cockroft, David L., and Denis Alan Trevor New. "Effects of Hyperthermia on Rat Embryos in Culture." Nature 258 (1975): 604-6.

11. Cockroft, David L., and Denis Alan Trevor New. "Abnormalities Induced in Cultured Rat Embryos by Hyperthermia." Teratology 17 (1978): 277-84.

12. Cohlan, Sidney Q. "Excessive Intake of Vitamin A as a Cause of Congenital Anomalies in the Rat." Science 117 (1953): 535-6.

13. Dareste, Camille. Recherches sur la production artificielle des monstruosités, ou, Essais de tératogénie expérimentale [Research on the production of artificial monstrosities, or, Essays on experimental teratology]. Paris: E. Reinwald, 1877 http://dx.doi.org/10.5962/bhl.title.45945 (Accessed January 8, 2014).

14. Edwards, Marshall J. "Hyperthermia as a Teratogen: A Review of Experimental Studies and Their Clinical Significance." Teratogenesis, Carcinogenesis, and Mutagenesis 6 (1986): 563-82.

15. Finnell, Richard H. "Teratology: General Consideration and Principles." Journal of Allergy and Clinical Immunology 103 (1999): 337-42.

16. Friedman, Jan M. "The Principles of Teratology: Are They Still True?" Birth Defects Research Part A: Clinical and Molecular Teratology 88 (2010): 766-8.

17. Garfield, Eugene. "Teratology Literature and the Thalidomide Controversy." In Essays of an Information Scientist. Philadelphia: ISI Press, 1986, 404-12.

18. Germain, Mary-Ann, William S. Webster, and Marshall J. Edwards. "Hyperthermia as a Teratogen: Parameters Determining Hyperthermia-Induced Head Defects in the Rat." Teratology 31 (1985): 265-72.

19. Goldstein, Leopold and Douglas P. Murphy. "Microcephalic Idiocy Following Radium Therapy for Uterine Cancer During Pregnancy." American Journal of Obstetrics and Gynecology 18 (1929): 89-95.

20. Graham Jr., John M., and Marshall J. Edwards. "Teratogenic Effects of Maternal Hyperthermia." Annals of the Research Institute of Environmental Medicine 40 (1989): 365-74.

21. Graham Jr., John M., Matthew J. Edwards, and Marshall J. Edwards. "Teratogen Update: Gestational Effects of Maternal Hyperthermia Due to Febrile Illnesses and Resultant Patterns of Defects in Humans." Teratology 58 (1998): 209-21.

22. Gregg, Norman McAlister. "Congenital Cataract Following German Measles in the Mother." Transactions of the Ophthalmological Society of Australia 3 (1941): 35-46. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2272051/ (Accessed January 8, 2014).

23. Hale, Fred. "Pigs Born Without Eyeballs." Journal of Heredity 24 (1933): 105-6. http://www.oxfordjournals.org/our_journals/jhered/freepdf/24-105.pdf (Accessed January 8, 2014).

24. Hellmann, Wilhelmine. "Endotoxin Fever and Anomalies of Development in Rabbits." Arzneimittel-Forschung 29 (1977): 1062-4.

25. Hill, Robert. "Model Systems and Their Predictive Value in Assessing Teratogens." Fundamental and Applied Toxicology 3 (1983): 229-32.

26. Kalter, Harold. "Teratology in the 20th Century: Environmental Causes of Congenital Malformations in Humans and How They Were Established." Neurotoxicology and Teratology 25 (2003): 131-282.

27. Lary, Joseph M., David L. Conover, Edward D. Foley, and Peggy L. Hanser. "Teratogenic Effects of 27.12 MHz Radiofrequency in Rats." Teratology 26 (1982): 299-309.

28. Lary, Joseph M., David L. Conover, Peggy H. Johnson, and Jenné A. Burg. "Teratogenicity of 27.12-MHz Radiation in Rats is Related to Duration of Hyperthermic Exposure." Bioelectromagnetics 4 (1983): 249-55.

29. Lenz, Widukind and Klais Knapp. "Thalidomide embryopathy." Archives of Environmental Health: An International Journal 5 (1962): 14-19.

30. Lipson, Anthony, John M. Optiz, and James F. Reynolds. "Hirschsprung Disease in the Offspring of Mothers Exposed to Hyperthermia During Pregnancy." American Journal of Medical Genetics 29 (1988): 117-24.

31. Little, Bertis B., Fred E. Ghali, Laura M. Snell, Kraig A. Knoll, W. Johnston, and Larry C. Gilstrap "Is Hyperthermia Teratogenic in the Human?" American Journal of Perinatology 8 (1991): 185-9.

32. Meyers, Vera Kolb. "Chemicals Which Cause Birth Defects-Teratogens: A Special Concern of Research Chemists." Science of the Total Environment 32 (1983): 1-12.

33. Murphy, Douglas P. "Ovarian Irradiation; Its Effects on the Health of Subsequent Children: Review of the Literature, Experimental and Clinical, with a Report of Three-Hundred and Twenty Human Pregnancies." Surgery, Gynecology, and Obstetrics 47 (1928): 201-5.

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Copyright Arizona Board of Regents Licensed as Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported (CC BY-NC-SA 3.0) http://creativecommons.org/licenses/by-nc-sa/3.0/

Teratogens; Abnormalities, Human; Fetus; Pregnancy; Teratogenicity testing; Embryos; Teratogenic agents; Human embryo; Fetus; Miscarriage; Thalidomide; Concept

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Teratogens Teratogens are substances that may produce physical or functional defects in the human embryo or fetus after the pregnant woman is exposed to the substance. Alcohol and cocaine are examples of such substances.

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Some examples are:

. some medicines
. Street drugs
. Alcohol
. Tobacco
. Toxic chemicals
. Some viruses and bacteria
Certain health conditions, such as uncontrolled diabetes

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Teratogens are substances that may produce physical or functional defects in the human embryo or fetus after the pregnant woman is exposed to the substance.

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This can occur in the first 10-14 days after conception

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What is a teratogen?

A teratogen (ter-AT-uh-jen) is something that can cause or raise the risk for a birth defect in a baby. They are things that a mother may be exposed to during her pregnancy. Teratogens include:

The riskiest times of pregnancy

Experts believe that teratogens can begin affecting a baby growing in the womb about 10 to14 days after conception. Conception is when a woman's egg is fertilized by a man's sperm. After conception, it takes about 6 to 9 days for the egg to implant in the uterus. Once the fertilized egg is attached to the uterus, the mother and the embryo share a blood supply. Chemicals in the mother's blood can then affect the growing baby.

As a baby grows in the womb, teratogens may affect parts of the baby's body as they are forming. For example, the neural tube closes in the first 3 to 5 weeks of the pregnancy. During this time, teratogens can cause neural tube defects such as spina bifida. Some organs are sensitive to teratogens during the whole pregnancy. This includes the baby's brain and spinal cord. Alcohol affects the brain and spinal cord, so it can cause harm at any time during pregnancy. This is why you should not drink alcohol if you are pregnant.

How are teratogens known?

Researchers have two ways of finding out if a substance is a teratogen. They are:

What are nonteratogenic agents?

Certain things have been shown to not cause birth defects. These are called nonteratogenic agents. These include:

Spermicides. These are chemicals that kill sperm to prevent pregnancy. These chemicals are found in products for birth control, such as gels, creams, and foams, and on some condoms. Studies have shown no link with the use of spermicides and any increased chance for birth defects.

Acetaminophen. This is a common ingredient in some pain medicines. There has been no link between birth defects and taking acetaminophen at the advised dose during pregnancy.

Prenatal vitamins. Prenatal vitamins are prescribed to pregnant women to help meet the extra nutritional needs of pregnancy. When used at the recommended dose, they don't increase the risk for birth defects. But don't take any extra vitamins, minerals, or herbal supplements without talking with your healthcare provider first. Extra amounts may be harmful.

Microwave ovens. Microwave ovens use nonionizing radiation. This type of radiation is not teratogenic. Microwaving food while pregnant is not known to increase the risk for birth defects or health problems.

Talking with your healthcare provider

If you're pregnant, talk with your healthcare provider about things to avoid during pregnancy that may cause birth defects. He or she can help answer your questions and help you have a safe pregnancy.

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teratogen; nonteratogenic agents; birth defects; alcohol; street drugs; tobacco; diabetes; toxic chemicals; neural tube defects; spina bifida; feta alcohol syndrome

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A teratogen (ter-AT-uh-jen) is something that can cause or raise the risk for a birth defect in a baby. They are things that a mother may be exposed to during her pregnancy. Teratogens include: Experts believe that teratogens can begin affecting a baby growing in the womb about 10 to14 days after conception.

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there is lots of examples of specific teratogens on this website!

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Teratogens are drugs, chemicals, or even infections that can cause abnormal fetal development. There are billions of potential teratogens, but only a few agents are proven to have teratogenic effects. These effects can result in a baby being born with a birth defect. Approximately 4 to 5 percent of birth defects are caused by exposure to a teratogen.

The majority of agents that people come into contact with aren't proven teratogens. Talk to your doctor if you're concerned about being exposed to a particular medication, chemical, or infection during pregnancy.

Researchers believe a teratogen can affect a developing fetus about 10 to14 days after conception.

The best way to reduce the risk of exposure to teratogens during pregnancy is to avoid taking medications when possible and to avoid exposure to the following:

Avoid prolonged stays in whirlpools, steam rooms, or saunas.

Talk to your doctor before you start taking any over-the-counter supplements during pregnancy. Products that claim to be natural may not necessarily be safe to use during pregnancy.

If your doctor orders a test with possible radiation exposure during your pregnancy, they must strongly believe that the risk of exposure is less than the risk of an untreated or undiagnosed condition. In most cases, the lower abdomen can be shielded with a protective apron to prevent exposure.

It isn't always possible to avoid sick children, and in most cases, exposures only lead to minor illnesses. When you can, it's best to avoid such exposures while you're pregnant. Every parent knows that the easiest place to acquire an illness is in a day care center or school, so avoid these locales as much as possible.

Certain infections can be passed from child to adult, including chickenpox, rubella, and cytomegalovirus (CMV). Adults are immune to many of these diseases. In some cases, however, the exposure may result in an infection that can affect the baby while in the womb. If you've been exposed to a known viral or bacterial illness, call your doctor right away so they can decide whether a blood test is needed.

Toxoplasmosis is an infection that can be transmitted from cat feces to humans. If you're pregnant and have a cat, you should minimize your exposure to the litter box as much as possible. Ask someone else in your household to clean the litter box. If you don't have anyone to help you with the litter, clean the litter box every day to reduce your risk of contracting toxoplasmosis. You don't need to get rid of your cat.

You should also avoid known teratogens. These include

angiotensin converting enzyme (ACE) inhibitors, such as Zestril and Prinivil

alcohol

aminopterin

androgens, such as methyltestosterone (Android)

busulfan (Myleran)

carbamazepine (Tegretol)

chlorobiphenyls

cocaine

coumarins

warfarin (Coumadin)

cyclophosphamide (Cytoxan)

danazol (Danocrine)

diethylstilbestrol (DES)

etretinate (Tegison)

isotretinoin (Accutane)

lead

lithium (Eskalith)

mercury

methimazole (Tapazole)

methotrexate (Rheumatrex)

penicillamine (Depen, Cuprimine)

phenytoin (Dilantin)

phenobarbital (Solfoton)

propylthiouracil (PTU)

prostaglandins

radioactive iodine

tetracycline (Sumycin)

tobacco

trimethadione (Tridione)

valproic acid (Depakene)

Some of these agents are easy to avoid. Others may be required for a medical condition and are unavoidable. For instance, you may require phenytoin to control your seizures if you're pregnant and you have epilepsy. Despite the risk of teratogenic effects, you may be better off taking the phenytoin than risking the occurrence of uncontrolled seizures during pregnancy.

If you need treatment with any of the medications that are known teratogens and you're pregnant, ask your doctor to send you to a geneticist. Geneticists specialize in the effects of teratogens on fetuses and can help you assess your actual risk given a specific exposure. You may also receive a targeted ultrasound evaluation to determine whether the fetus has been affected in some way.

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Pregnancy and Teratogens: What You Need to Know

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Teratogens are drugs, chemicals, or even infections that can cause abnormal fetal development. There are billions of potential teratogens, but only a few agents are proven to have teratogenic effects. These effects can result in a baby being born with a birth defect.

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How many examples of specific teratogens can you find?

Link your findings to this comment.

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Descriptions,  definitions, and links to useful sources of information

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Descriptions,  definitions, and links to useful sources of information

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Create your own posts using the plus in the bottom corner, then right-click on your own posts to link them with existing posts on the board