2.8: Teratogens

Good prenatal care is essential to protect against parental and fetal/infant mortality and birth complications. The embryo and fetus 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 biological parents are unaware that they are pregnant. Today, we know many of the factors that can jeopardize the health of the developing organism. Teratogens are harmful agents/conditions in pregnancy that can contribute to birth defects, and include some parental diseases, pollutants, drugs and alcohol; and the study of factors that are harmful to a developing organism in utero is called teratology.

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 type of exposure: For example, depending on whether there is exposure to alcohol or tobacco, the results for the fetus and resultant child will be different. Fetal Alcohol Syndrome is qualitatively and substantially different from Fetal Tobacco Syndrome.
• 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 the embryo is exposed to certain substances during this period, the arms and ears may be malformed. (see figure below)
• 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 of the organism and metabolism of the pregnant individual.
• The interaction of teratogens: Fetuses exposed to multiple teratogens typically have more problems than those exposed to only one.
• Genetics: Genetic makeup 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 not experiencing the same effects. The genetic makeup of the biological parents can also have an effect; some may be more resistant to teratogenic effects than others.
• Being male or female: Biological male offspring are more likely to experience damage due to teratogens than are biological females. It is believed that the Y chromosome, which contains fewer genes than the X, may have an impact.[1]

  

  Figure \(\PageIndex{1}\): The development of an embryo into a fetus, and therefore what parts are most susceptible to harm at particular stages of prenatal development. The figure shows that in the germinal period, teratogenic effects are most likely to result in spontaneous abortion or miscarriage. In the embryonic period, when most critical periods are, teratogenic effects are most likely to result in major morphological abnormalities. In the fetal period, teratogenic effects are most likely to result in functional defects and minor morphological abnormalities.[2]

There are four categories of teratogens:

1. Physical teratogens: These could be saunas, hot tubs, or infections that raise a pregnant person's body temperature to 102 degrees Fahrenheit or higher. This is associated with neural tube defects, spontaneous abortions, and various cardiovascular abnormalities.
2. Metabolic conditions affecting pregnant females: 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 person is malnourished, then their fetus likely lacks the nutrients essential for its development. These include malnutrition, diabetes, and thyroid disorders.
3. Infections: Different parental infections, including rubella virus, herpes simplex virus, and syphilis can cause congenital abnormalities in fetuses.
4. Drugs and chemicals: When pregnant individuals ingest or absorb these, they may cause a variety of different effects based on specific agent, amount of exposure, and timing. This category includes radiation, heavy metals (including lead), insecticides and herbicides, prescription and over the counter drugs, illicit and recreational drugs, alcohol, cigarettes, nicotine, caffeine, and even some vitamins.[3]

While there are many, many potential teratogens, the following tables look at the effects of some different types of teratogens. The risks of exposure vary based on lifestyle and health. The effects may vary greatly depending on the factors mentioned previously. Protection and prevention will vary based on the method of exposure.

Drugs as Teratogens

Table \(\PageIndex{1}\): Drugs as Teratogens

Teratogen	Potential Effects
Caffeine	Moderate amounts of caffeine (200 mg or around 12 ounces of coffee) appear to be safe during pregnancy. Some studies have shown a link between higher amounts of caffeine and miscarriage and preterm birth.[4]
Tobacco	Tobacco use has been associated with low birth weight, placenta previa, preterm delivery, fetal growth restriction, sudden infant death syndrome, cleft lip or palate, and later health problems (such as high blood pressure and diabetes).[5]
Alcohol	There is no safe amount of alcohol a woman can drink while pregnant. Alcohol can slow down the fetus's growth, affect the developing brain, and cause birth defects, and may results in fetal alcohol spectrum disorder (FASD). The effects can be mild to severe. Children born with a severe form of FASD can have specific facial features, severe learning disabilities, behavioral problems, and other problems.[6]
Cocaine	Cocaine use has been connected with low birth weight, stillbirths, spontaneous abortion, placental abruption, premature birth, miscarriage, and neonatal abstinence syndrome (fetal addiction leads the newborn to experience withdrawal).[7]
Marijuana	No amount of marijuana has been proven safe to use during pregnancy. Heavy use has been associated with brain damage, premature birth, and stillbirth.[8]
Heroin	Using heroin during pregnancy can cause birth defects, placental abruption, premature birth, low birthweight, neonatal abstinence syndrome, still birth, and sudden infant death syndrome.[9]
Over-the-Counter (OTC) medication	Some OTC medications are safe to use during pregnancy and others may cause health problems during pregnancy. Pregnant individuals should consult their health care provider before using any OTC medications.[10]
Prescription drugs	Some prescription drugs can cause birth defects that change the shape or function of one or more parts of the body that can affect overall health. Pregnant individuals should consult their health care provider before discontinuing or starting new medications.[11]
Herbal or dietary supplements	Except for some vitamins, little is known about using herbal or dietary supplements while pregnant. Most often there are no good studies to show if the herb can cause harm during pregnancy. Also, some herbs that are safe when used in small amounts as food might be harmful when used in large amounts as medicines.[12]

Environmental Teratogens

Table \(\PageIndex{2}\): Environmental agents as teratogens

Teratogen	Potential Effects
Lead	Exposure to high levels of lead before and during pregnancy can lead to high blood pressure, problems with fetal brain and nervous system development, premature birth, low birthweight, and miscarriage.[13]
Mercury	Exposure to mercury in the womb can cause brain damage and hearing and vision problems.[14]
Radiation	Exposure to radiation during pregnancy (especially between 2 and 18 weeks of pregnancy) can slow growth, cause birth defects, affect brain development, cause cancer, and cause miscarriage.[15]
Solvents	These chemicals include degreasers, paint thinners, stain and varnish removers, paints, and more. Inhalation of solvents during pregnancy can cause fetal exposure leading to miscarriage, slow fetal growth, premature birth, and birth defects.[16]

Maternal Infections as Teratogens

Table \(\PageIndex{3}\): Maternal infections as Teratogens

Teratogen	Potential Effects
Rubella	Congenital infection (becoming infected while in the womb) can damage the development of the eyes, ears, heart, and brain and result in deafness.[17]
Zika	Congenital infection can cause microcephaly and other severe brain abnormalities.[18]
Varicella (chicken pox)	Congenital infection can cause a severe form of the infection affecting the eyes, limbs, skin, and central nervous system.[19]
Sexually transmitted infections	Infections such as HIV, gonorrhea, syphilis, and chlamydia can be passed from the pregnant person during pregnancy and/or delivery.[20]
Listeria	Pregnant individuals are more susceptible to this food-borne illness. Congenital infection can cause miscarriage, stillbirth, premature labor, and neonatal sepsis.[21]

Teratogens from Animals/Pets

Table \(\PageIndex{4}\): Teratogens from Animals/Pets

Teratogen	Potential Effects
Toxoplamosis	This parasite can be passed through cat feces and undercooked meat (especially pork, lamb, or deer meet). If the fetus is infected it can cause miscarriage, stillbirth, hydrocephalus, macro or microcephalus, vision issues, and damage to the nervous system.[22]
Lymphocytic choriomeningitis	This virus carried by rodents including mice, hamsters, and guinea pigs. If passed to the fetus it can cause issues with brain development, long-term neurological and/or visual impairment, and higher mortality rates after birth.[23]

Parental Factors

There are additional factors that affect the outcome of pregnancy for both pregnant individual and prospective child. Let’s look at these next.

Pregnancy over age 35

Most people over 35 who become pregnant are in good health and have healthy pregnancies. However, according to the March of Dimes (2016d), biological females over age 35 are more likely to have an increased risk of:

• Fertility problems
• High blood pressure
• Diabetes
• Miscarriages
• Placenta Previa
• Cesarean section
• Premature birth
• Stillbirth
• A baby with a genetic disorder or other birth defects

Because a biological female is born with all their eggs, environmental teratogens can affect the quality of those eggs as the person grows older. Also, the reproductive system ages which can adversely affect the pregnancy. Special prenatal screening tests, such as a maternal blood screening, are generally available to determine if there are any health risks for the fetus.

Although there are medical concerns associated with having a child later in life, there are also many positive consequences to being a more mature parent. Older parents are more confident, less stressed, and typically more likely to be married, providing family stability. Their children perform better on math and reading tests, and they are less prone to injuries or emotional troubles (Albert, 2013). People who choose to wait to get pregnant are often well educated and lead healthy lives. According to Gregory (2007), older parents are more stable, demonstrate a stronger family focus, possess greater self-confidence, and have more money. Having a child later in one’s career equals overall higher wages. In fact, for every year a woman delays motherhood, she makes 9% more in lifetime earnings. Lastly, women who delay having children actually live longer.

Teenage Pregnancy

A teenage pregnant person is at a greater risk for having pregnancy complications including anemia, and high blood pressure. These risks are even greater for those under age 15. Infants born to teens have a higher risk for being premature and having low birthweight or other serious health problems. Premature and low birthweight babies may have organs that are not fully developed which can result in breathing problems, bleeding in the brain, vision loss, serious intestinal problems, and higher likelihood of dying. Reasons for these health issues include that teenagers are the least likely of all age groups to get early and regular prenatal care and they may engage in negative behaviors including eating unhealthy food, smoking, drinking alcohol, and taking drugs.

Gestational Diabetes

Seven percent of pregnant individuals develop gestational diabetes (March of Dimes, 2015b). Diabetes is a condition where the body has too much glucose in the bloodstream.

Figure \(\PageIndex{2}\): Individuals diagnosed with gestational diabetes need to test, chart and maintain their sugar levels.[25]

Most pregnant individuals have their glucose level tested between 24 to 28 weeks of pregnancy. Gestational diabetes usually goes away after giving birth, but it might indicate a risk for developing diabetes later in life. If untreated, gestational diabetes can cause premature birth, stillbirth, the baby having breathing problems at birth, jaundice, or low blood sugar. Babies born to persons with gestational diabetes can also be considerably heavier (more than 9 pounds) making the labor and birth process more difficult. For expectant individuals, untreated gestational diabetes can cause preeclampsia (high blood pressure and signs that the liver and kidneys may not be working properly) discussed in another section.

Risk factors for gestational diabetes include age (being over age 25), being overweight or gaining too much weight during pregnancy, family history of diabetes, having had gestational diabetes with a prior pregnancy, and race and ethnicity (African-American, Native American, Hispanic, Asian, or Pacific Islander have a higher risk). Eating healthy and maintaining a healthy weight during pregnancy can reduce the chance of gestational diabetes. People who already have diabetes and become pregnant need to attend all their prenatal care visits, and follow the same advice as those for people with gestational diabetes as the risk of preeclampsia, premature birth, birth defects, and stillbirth are the same.

High Blood Pressure (Hypertension)

Hypertension is a condition in which the pressure against the wall of the arteries becomes too high. There are two types of high blood pressure during pregnancy, gestational and chronic. Gestational hypertension only occurs during pregnancy and goes away after birth. Chronic high blood pressure refers to individuals who already had hypertension before the pregnancy or to those who developed it during pregnancy and it did not go away after birth.

Figure \(\PageIndex{3}\): At every prenatal visit the pregnant individual’s blood pressure is checked, because high blood pressure is indicative of possible problems with the fetus and birth complications.[26]

According to the March of Dimes (2015c), about 8 in every 100 pregnant people have high blood pressure. High blood pressure during pregnancy can cause premature birth and low birth weight (under five and a half pounds), placental abruption, and preeclampsia.

Rh Incompatibility

Rh is a protein found in the blood. Most people are Rh positive, meaning they have this protein. Some people are Rh negative, meaning this protein is absent. Pregnant individuals who are Rh negative are at risk of having a baby with a form of anemia called Rh disease (March of Dimes, 2009). With just one Rh positive gene, the organism will be a carrier for Rh-negative, but be Rh-positive themselves. A biological male who is Rh-positive and biological female who is Rh-negative can conceive a baby who is Rh-positive. Some of the fetus’s blood cells may get into the pregnant person’s bloodstream and their immune system is unable to recognize the Rh factor. The immune system starts to produce antibodies to fight off what it thinks is a foreign invader. Once their body produces immunity, the antibodies can cross the placenta and start to destroy the red blood cells of the developing fetus. As this process takes time, often the first Rh positive baby is not harmed, but as the biological parent’s body will continue to produce antibodies to the Rh factor across their lifetime, subsequent pregnancies can pose greater risk for an Rh positive baby. In the newborn, Rh disease can lead to jaundice, anemia, heart failure, brain damage and death.

Weight Gain during Pregnancy

According to March of Dimes (2016f), during pregnancy most people need only an additional 300 calories per day to aid in the growth of the fetus. Gaining too little or too much weight during pregnancy can be harmful. People who gain too little may have a baby who is low-birth weight, while those who gain too much are likely to have a premature or large baby. There is also a greater risk for developing preeclampsia and diabetes, which can cause further problems during the pregnancy.

The table below shows the healthy weight gain during pregnancy. Putting on the weight slowly is best. Individuals who are concerned about their weight gain should talk to their health care provider.

Table \(\PageIndex{5}\): Desirable weight gain in pregnancy

If you were a healthy weight before pregnancy:	If you were underweight before pregnancy:	If you were overweight before pregnancy:	If you were obese before pregnancy:
Gain 25-35 pounds 1-4½ pounds in the 1^st trimester 1 pound per week in the 2^nd and 3^rd trimesters	Gain 28-30 pounds 1-4½ pounds in the 1^st trimester A little more than 1 pound per week thereafter	Gain 12-25 pounds 1-4½ pounds in the 1^st trimester A little more than ½ pound per week in 2^nd and 3^rd trimesters	11-20 pounds 1-4½ pounds in the 1^st trimester A little more than ½ pound per week in 2^nd and 3^rd trimesters
Mothers of twins or higher order multiples need to gain more in each category.

Stress

Feeling stressed is common during pregnancy, but high levels of stress can cause complications including having a premature baby or a low-birthweight baby. Babies born early or too small are at an increased risk for health problems. Stress-related hormones may cause these complications by affecting a pregnant person’s immune systems resulting in an infection and premature birth. Additionally, some people deal with stress by smoking, drinking alcohol, or taking drugs, which can lead to problems in the pregnancy. High levels of stress in pregnancy have also been correlated with problems in the fetus’s brain development and immune system functioning, as well as childhood problems such as trouble paying attention and being afraid (March of Dimes, 2012b).

Depression

Depression is a significant medical condition in which feelings of sadness, worthlessness, guilt, and fatigue interfere with one’s daily functioning. Depression can occur before, during, or after pregnancy, and 1 in 7 people are treated for depression sometime between the year before pregnancy and year after pregnancy (March of Dimes, 2015a). Those who have experienced depression previously are more likely to have depression during pregnancy. Consequences of depression include the baby being born premature, having a low birthweight, being more irritable, less active, less attentive, and having fewer facial expressions.

About 13% of pregnant individuals take an antidepressant during pregnancy. It is important that they discuss the medication with a health care provider as some medications can cause harm to the developing organism.

Paternal Impact

The age of biological fathers at the time of conception is also an important factor in health risks for children. According to Nippoldt (2015), offspring of men over 40 face an increased risk of miscarriages, autism, birth defects, achondroplasia (bone growth disorder) and schizophrenia. These increased health risks are thought to be due to accumulated chromosomal aberrations and mutations during the maturation of sperm cells in older men (Rahbari et al, 2016). However, like older women, the overall risks are small.

Figure \(\PageIndex{4}\): Exposure to hazardous chemicals is of particular concern during pregnancy and has been found to adversely affect birth outcomes.[28]

Attributions:

Child Growth and Development by Jennifer Paris, Antoinette Ricardo, and Dawn Rymond, 2019, is licensed under CC BY 4.0

[1] Lifespan Development: A Psychological Perspective (pages 46-47) by Martha Lally and Suzanne Valentine-French is licensed under CC BY-NC-SA 3.0

[2] Image by Laura Overstreet is licensed under CC BY-NC-SA 3.0

[3] The Embryo Project Encyclopedia by Chanapa Tantibanchachai is licensed under CC BY-NC-SA 3.0

[4] Staying healthy and safe by OWH is in the public domain

[5] Chapter 3: Prenatal Development – Environmental Risks references Psyc 200 Lifespan Psychology by Laura Overstreet, which is licensed under CC BY 4.0;

Staying healthy and safe by OWH is in the public domain

[6] Staying healthy and safe by OWH is in the public domain

[7] Chapter 3: Prenatal Development – Environmental Risks references Psyc 200 Lifespan Psychology by Laura Overstreet, which is licensed under CC BY 4.0;

Prescription drugs, over-the-counter drugs, supplements and herbal products (n.d.). Retrieved from: https://www.marchofdimes.org/pregnancy/prescription-drugs-over-the-counter-drugs-supplements-and-herbal-products.aspx

[8] Chapter 3: Prenatal Development – Environmental Risks references Psyc 200 Lifespan Psychology by Laura Overstreet, which is licensed under CC BY 4.0;

Prescription drugs, over-the-counter drugs, supplements and herbal products (n.d.). Retrieved from: https://www.marchofdimes.org/pregnancy/prescription-drugs-over-the-counter-drugs-supplements-and-herbal-products.aspx

[9] Prescription drugs, over-the-counter drugs, supplements and herbal products (n.d.). Retrieved from: https://www.marchofdimes.org/pregnancy/prescription-drugs-over-the-counter-drugs-supplements-and-herbal-products.aspx

[10] Prescription drugs, over-the-counter drugs, supplements and herbal products (n.d.). Retrieved from: https://www.marchofdimes.org/pregnancy/prescription-drugs-over-the-counter-drugs-supplements-and-herbal-products.aspx

[11] Prescription drugs, over-the-counter drugs, supplements and herbal products (n.d.). Retrieved from: https://www.marchofdimes.org/pregnancy/prescription-drugs-over-the-counter-drugs-supplements-and-herbal-products.aspx

[12] Chapter 3: Prenatal Development – Environmental Risks references Psyc 200 Lifespan Psychology by Laura Overstreet, which is licensed under CC BY 4.0

[13] Prescription drugs, over-the-counter drugs, supplements and herbal products (n.d.). Retrieved from: https://www.marchofdimes.org/pregnancy/prescription-drugs-over-the-counter-drugs-supplements-and-herbal-products.aspx

[14] Prescription drugs, over-the-counter drugs, supplements and herbal products (n.d.). Retrieved from: https://www.marchofdimes.org/pregnancy/prescription-drugs-over-the-counter-drugs-supplements-and-herbal-products.aspx

[15] Prescription drugs, over-the-counter drugs, supplements and herbal products (n.d.). Retrieved from: https://www.marchofdimes.org/pregnancy/prescription-drugs-over-the-counter-drugs-supplements-and-herbal-products.aspx

[16] Prescription drugs, over-the-counter drugs, supplements and herbal products (n.d.). Retrieved from: https://www.marchofdimes.org/pregnancy/prescription-drugs-over-the-counter-drugs-supplements-and-herbal-products.aspx

[17] Chapter 3: Prenatal Development – Environmental Risks references Psyc 200 Lifespan Psychology by Laura Overstreet, which is licensed under CC BY 4.0

[18] Protocols on prenatal care for pregnant women with Zika infection and children with microcephaly: nutritional approach by Rachel de Sá Barreto Luna Callou Cruz, Malaquias Batista Filho, Maria de Fátima Costa Caminha, and Edvaldo da Silva Souza is licensed under CC BY 4.0

[19] Congenital Varicella syndrome by WikiDoc is licensed under CC BY-SA 3.0

[20] Chapter 3: Prenatal Development – Environmental Risks references Psyc 200 Lifespan Psychology by Laura Overstreet, which is licensed under CC BY 4.0

[21] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2860824/

[22] Prescription drugs, over-the-counter drugs, supplements and herbal products (n.d.). Retrieved from: https://www.marchofdimes.org/pregnancy/prescription-drugs-over-the-counter-drugs-supplements-and-herbal-products.aspx

[23] Prescription drugs, over-the-counter drugs, supplements and herbal products (n.d.). Retrieved from: https://www.marchofdimes.org/pregnancy/prescription-drugs-over-the-counter-drugs-supplements-and-herbal-products.aspx

[24] Image by Thomas Pompernigg is licensed under CC BY-SA 2.0

[25] Image by Jessica Merz is licensed under CC BY 2.0

[26] Image by rawpixel on Unsplash

[27] Lifespan Development: A Psychological Perspective (pages 52-55) by Martha Lally and Suzanne Valentine-French is licensed under CC BY-NC-SA 3.0

[28] Image by USDA is in the public domain