In
humans,
congenital disorders resulted in about 510,000 deaths globally in 2010. About 3% of newborns have a "major physical anomaly", meaning a physical anomaly that has cosmetic or functional significance. Developmental defects manifest in approximately 3% to 5% of newborns in the United States, between 2% and 3% of which are teratogen-induced. Congenital disorders are responsible for 20% of infant deaths. The most common congenital diseases are heart defects,
Down syndrome, and neural tube defects. Trisomy 21 is the most common type of Down syndrome. About 95% of infants born with Down syndrome have this disorder and it consists of three separate copies of chromosomes.
Translocation Down syndrome is not as common, as only 3% of infants with Down syndrome are diagnosed with this type. VSD, ventricular septal defect, is the most common type of heart defect in infants. If an infant has a large VSD it can result into heart failure. Infants with a smaller VSD have a 96% survival rate and those with a moderate VSD have about an 86% survival rate. Lastly, NTD, neural tube defect, is a defect that forms in the brain and spine during early development. If the spinal cord is exposed and touching the skin it can require surgery to prevent an infection.
Medications Though many pregnancies are accompanied with prescription drugs, there is limited knowledge regarding the potential teratogenic risks. Only medications that are commonly taken during pregnancies that are known to cause structural birth defects are considered teratogenic agents. One common drug in particular that is teratogenic is isotretinoin, known by many as Accutane. It became popular through its success in the care and treatment of skin cancer and severe acne. However, over time it has become clear that it causes severe teratogenic effects with 20-35% of exposed embryos experiencing developmental defects. Exposure of isotretinoin has led to severe skull, facial, cardiovascular, and neurological defects. Another drug known as carbamazepine is sometimes prescribed during pregnancy if the mother experiences more extreme concerns regarding epilepsy or bipolar disorder. Unfortunately, this drug can also cause birth and developmental defects especially during the early stages of pregnancy such as defects of the neural tube, which develops into the brain and spinal cord. An example of this is spina bifida. Oral and topical antifungal agents such as fluconazole, ketoconazole, and terbinafine are commonly prescribed in pregnancy. Some fungal infections are asymptomatic and therefore do not really cause discomfort, but some are slightly more severe and can negatively affect a pregnant woman's life quality and even the fetus. This is primarily when antifungal agents are prescribed during pregnancy. Unfortunately, the use of antifungal agents can lead to spontaneous abortions and defects mainly regarding the cardiovascular and musculoskeletal systems, as well as some eye defects. It is safer to avoid taking medications during pregnancy to keep the likelihood of teratogenicity low, as the chances of any pregnancy resulting in birth defects is only 3-5%. However, it is necessary and cannot be avoided in certain cases. As with any medical concern, a doctor should always be consulted in order for the pregnancy to have the best outcome possible for both mother and baby.
Acitretin Acitretin is a retinoid and vitamin A derivative that is used in the treatment of psoriasis.
Acitretin is highly teratogenic and noted for the possibility of severe birth defects. It was initially suggested as a replacement for Etretinate. It should not be used by pregnant women or women planning to get pregnant within 3 years following the use of acitretin. Sexually active women of childbearing age who use acitretin should also use at least two forms of birth control concurrently. Men and women who use it should not donate blood for three years after using it, because of the possibility that the blood might be used in a pregnant patient and cause birth defects. In addition, it may cause nausea, headache, itching, dry, red or flaky skin, dry or red eyes, dry or chapped lips, swollen lips, dry mouth, thirst,
cystic acne or hair loss.
Etretinate Etretinate (trade name Tegison) is a
medication developed by
Hoffmann–La Roche that was approved by the FDA in 1986 to treat severe
psoriasis. It is a second-generation
retinoid. It was subsequently removed from the
Canadian market in 1996 and the
United States market in 1998 due to the high risk of birth defects. It remains on the market in Japan as Tigason.
Isotretinoin Isotretinoin is classified as a retinoid drug and is used as a treatment for severe acne, other skin conditions, and some cancer types. In treatment against acne, it functions by hindering the activity of skin's sebaceous glands. It is extremely effective in its use in treatment against severe acne, but does have some negative side effects such as dry skin, nausea, joint and muscle pain, blistering skin, and the development of sores on mucous membranes. Isotretinoin is able to cross the placenta, potentially harming the developing fetus. If a fetus is exposed to isotretinoin during the first trimester of pregnancy, craniofacial, cardiac, and central nervous system malformations can occur. Some prenatal exposures to isotretinoin can result in still births or spontaneous abortions.
Vaccination In
humans,
vaccination has become readily available, and is important for the prevention of various communicable diseases such as
polio and
rubella, among others. There has been no association between congenital malformations and vaccination — for example, a population-wide study in Finland in which expectant mothers received the oral polio vaccine found no difference in infant outcomes when compared with mothers from reference cohorts who had not received the vaccine. However, on grounds of theoretical risk, it is still not recommended to vaccinate for polio while pregnant unless there is risk of infection. An important exception to this relates to provision of the influenza vaccine while pregnant. During the
1918 and
1957 influenza pandemics, mortality from influenza in pregnant women was 45%. In a 2005 study of vaccination during pregnancy, Munoz et al. demonstrated that there was no adverse outcome observed in the new infants or mothers, suggesting that the balance of risk between infection and vaccination favored preventative vaccination.
Reproductive hormones and hormone replacement therapy There are a number of ways that a fetus can be affected in pregnancy, specifically due to exposure to various substances. There are a number of drugs that can do this, specifically drugs such as female
reproductive hormones or hormone replacement drugs such as
estrogen and
progesterone that are not only essential for reproductive health, but also pose concerns when it comes to the synthetic alternatives to these. This can cause a multitude of congenital abnormalities and deformities, many of which can ultimately affect the fetus and even the mother's reproductive system in the long term. According to a study conducted from 2015 till 2018, it was found that there was an increased risk of both maternal and neonatal complications developing as a result of
hormone replacement therapy cycles being conducted during pregnancy, especially in regards to hormones such as estrogen,
testosterone and thyroid hormone. When hormones such as estrogen and testosterone are replaced, this can cause the fetus to become stunted in growth, born prematurely with a lower birth weight, develop intellectual disability, while in turn causing the mother's ovarian reserve to be depleted while increasing ovarian follicular recruitment.
Chemotherapeutic agents It is rare for cancer and pregnancy to coincide, occurring in only 1 in 1,000 pregnancies and making up less than 0.1% of all recorded malignant tumors. However, when this does occur, there are many complications and great, although not well understood, risks to the fetus in the event that
chemotherapy drugs are used. The majority of these drugs are cytotoxic, meaning that they have the potential to be
carcinogenic, mutagenic, and teratogenic. If used during the first two weeks of pregnancy, they may inhibit implantation of the fetus and led to miscarriage. Chemotherapeutic drugs are considered safer to use during the second and third trimester, but there is limited research to fully support this.
Thalidomide agent.
Thalidomide, also known as Thalomid, was used in the mid-1900s primarily, as a sedative. It is a drug that was first introduced in Germany and spread to other countries as a therapeutic prescription from the 1950s to early 1960s in Europe as an anti-nausea medication to alleviate morning sickness among pregnant women. While the exact mechanism of action of thalidomide is not known, it is thought to be related to inhibition of
angiogenesis through interaction with the insulin like growth factor(IGF-1) and fibroblast like growth factor 2 (FGF-2) pathways. As it became more well known, other uses were found, such as its use in
leprosy treatment,
cancer treatment, and
HIV infections. PAE remains the leading cause of birth defects and neurodevelopmental abnormalities in the United States, affecting 9.1 to 50 per 1,000 live births in the U.S. and 68.0 to 89.2 per 1,000 in populations with high levels of alcohol use.
Tobacco and Nicotine Consuming
tobacco products while pregnant or breastfeeding can have significant negative impacts on the health and development of the unborn child and newborn infant. In a research study conducted in 1957, the relationship between tobacco consumption during pregnancy and premature births was studied. It can be harmful to the developing fetus' brain and lungs. The liquid also contains artificial flavoring agents that can be harmful to the body. Some common teratogenic defects caused by cocaine include
hydronephrosis,
cleft palate,
polydactyly, and
down syndrome. Because cocaine is able to pass through the placenta and enter the fetus, the fetus' circulation can be negatively affected. With restriction of fetal circulation, the development of organs in the fetus can be impacted, even resulting in
intestines developing outside of the fetus' body. The
neurodevelopmental effects include sleep disturbances, hyperactivity, increased delinquency, and worsened problem-solving. It is advised that mothers refrain from using any products containing
THC while they are breastfeeding or pregnant.
Caffeine Caffeine consumption during pregnancy has been linked to intrauterine growth retardation and spontaneous abortion during the first trimester. Other teratogenic effects include low birthweight, problems with neural tube development, decreased head circumference, excessive infant growth, and cognitive impairments at birth. Caffeine's chemical structure allows it to be transmitted across biological membranes, including the placental barrier, which is then transmitted to the developing embryo. The inability to break down caffeine results in a build up of caffeine in the embryo. The build up of caffeine in embryos can produce teratogenic effects by blocking adenosine receptors, which regulate several neurotransmitters, including dopamine, serotonin, norepinephrine, and GABA. The teratogenic effects of caffeine are variable, and affects individuals differently depending on their sensitivity to caffeine. One mother may not have any teratogenic effects from caffeine consumption during pregnancy, while another could have significant complications.
Physical Agents as Teratogenic Agents Heat One example of a physical agent which may give rise to developmental complications is heat. Women may be exposed to heat from external sources such as extreme heat conditions and hot-tub exposures. External temperatures that exceed 102 °Fahrenheit can give rise to fetal complications via the mechanism of neural tube malformation. The exact mechanisms relating heat to neural tube defects are not well-known. A potential theory connects heat to multiple cell-related issues, including cell movement, cell division, and apoptosis. The disruption in these normal processes may ultimately feed into the mechanism of neural tube malformation. Another method of exposure to heat can be seen as a result of the pregnancy itself. This phenomenon can be associated with maternal weight gain as well the heat produced via fetal metabolism, both of which may cause dysregulation of heat escape. The exact mechanisms beyond these surface-level causes are not clear. One theory associates this heat with producing heat-shock proteins, which then disrupt a certain normal protein balance. This deviation from a normal protein balance may then interfere with fetal development. Another theory draws potential connections between elevated temperature, oxidative stress, and inflammation with blood flow restriction to the fetus.
Radiation Although large exposures to radiation during pregnancies are often rare, when such exposures occur the resulting teratogenic complications occur due to various factors and/or mechanisms. The negative effects associated with radiation in general have to do with the interaction of said radiation with the stem cells of the developing fetus. There are also associations with DNA damage, oxidative stress responses, and changes in protein expression. In terms of ionizing radiation in particular, such forms of radiation often cause chemical changes to occur that yields abnormal chemical species. These chemical materials can then act on two different structures: they can either alter specific tissue-level structures in a predictable way, or act on DNA structures in a more random fashion.
Noise While some ranges of sound are kept from reaching the fetus due to the presence of the mother's abdomen and uterus as barrier of sorts, there is still evidence that both high intensity sounds and continuous exposure to sound can be harmful to the fetus. Such sounds may bring about many potential problems within the fetus, including chromosomal abnormalities, altered social behavior after birth, and issues with hearing. In terms of hearing damage specifically, it is thought that these external sounds cause damage to the developing fetal cochlea and its constituent parts, particularly the inner and outer hairs of the structure.
Lead exposure Long before modern science, it was understood that heavy metals could cause negative effects to those who were exposed. The Greek physician
Pedanius Dioscorides described the effects of lead exposure as something that "makes the mind give way". Lead exposure in adults can lead to cardiological, renal, reproductive, and cognitive issues that are often irreversible, however, lead exposure during pregnancy can be detrimental to the long-term health of the fetus. Exposure to lead during pregnancy is well known to have teratogenic effects on the development of a fetus. Specifically, fetal exposure to lead can cause cognitive impairment, premature births, unplanned abortions, ADHD, and much more. Lead exposure during the first trimester of pregnancy leads to the greatest predictability of cognitive development issues after birth. A well-known recent example of lead and the impacts it can have on a was the
2014 water crisis in Flint, Michigan. Researchers have found that female fetuses developed at a higher rate than male fetuses in Flint when compared to surrounding areas. The higher rate of female births indicated a problem because male fetuses are more sensitive to pregnancy hazards than female fetuses.
Phthalate exposure Phthalate acid esters (PAEs) are a classification of chemical plasticizers used to increase flexibility in commercial plastics, such as polyethylene terephthalate (PET) and polyvinyl chloride (PVC). Phthalates are currently used in several consumer goods, including food packaging, cosmetics, clothing, fragrance, and toys. Additionally, they have wide-spread use in pharmaceutical and medical products, including in coatings and fillers of extend-release medications, blood bag packaging, tubes used in blood transfers, and hemodialysis units. The most common phthalates include di(2-ethylhexyl) phthalate and di-n-butyl phthalate. As of 2017, di(2-ethylhexyl) phthalate is estimated to make up 30% of plastic produced in the United States and European Union, vascular malformations, decreased bodyweight The use of di-n-butyl phthalate in children's products was restricted in the United States in 2008, and is restricted in cosmetics in the European Union. Several phthalates, including di-n-butyl phthalate, di-n-hexyl phthalate, and butyl benzyl phthalate, were issued a Proposition 65 warning by the state of California in March, 2005 following evidence of reproductive toxicity and teratogenic effects.
Stress Maternal stress has been associated with an increased risk of various birth defects, though a direct causal relationship has not been conclusively established. Studies suggest that the exposure to significant psychological stress or traumatic events during pregnancy may correlate with a higher incidence of congenital anomalies, such as oral facial cleft (cleft lip and palate), neural tube defects and conotruncal heart defects. One proposed mechanisms involves the dysregulation of maternal stress hormones, particularly glucocorticoids, which include cortisol and other corticosteroids. These hormones, often referred to as "stress hormones", are capable of crossing the placental barrier, but their effects on the fetus depends on the timing, duration, and intensity of exposure. The placenta expresses various enzymes, which metabolizes active cortisol into its inactive form, protecting the fetus. However extreme physiological responses or chronic stress could overwhelm this protective factor. Additionally, stress-induced changes in maternal physiology, such as reduced uteroplacental blood flow, inflammation, and oxidative stress, may further contribute to developmental disruptions. Sometimes, corticosteroids are used therapeutically to promote fetal lung maturation in preterm labor, excessive or prolonged exposure has been linked to intrauterine growth restriction and altered fetal programming. Further research is needed to clarify the exact role of maternal stress in teratogenesis and to determine the potential long-term impacts on offspring health.
Nutrient Deficiencies Micronutrient deficiencies during pregnancy can contribute to teratogenesis by disrupting essential developmental processes. Deficiencies in folate, iodine, vitamin A, and other key nutrients have been linked to congenital anomalies, miscarriage, and impaired fetal growth. These deficiencies impair cellular differentiation, gene expression, and organogenesis, making proper maternal nutrition crucial for fetal development. Prevention strategies include dietary supplementation and food fortification programs to reduce the incidence of birth defects worldwide.
Folate Deficiency Folate deficiency increases the risk of neural tube defects. It has been shown that supplementation of folate before, during, and after conception is able to reduce the risk of a fetus developing neural tube defects, cardiovascular malformations, cleft lip and palate, urogenital abnormalities, and reduced limb size.
Iodine Deficiency In mothers, an iodine deficiency can lead to hypothyroidism, increasing the chances for miscarriage to occur.
Hypothyroidism can also potentially cause growth problems in the baby, increasing the chances for preterm delivery. If the iodine deficiency is severe, the likelihood of stillbirth is increased as well as the child having the potential for increased hearing problems.
Zinc Deficiency Zinc deficiency can result in fetal death, intrauterine growth retardation, and teratogenesis. It can also have postnatal effects, such as behavioral abnormalities, elevated risk of high blood pressure, or impaired cognitive abilities. == Other animals ==