Pregnant women want definitive answers to their safety-related questions regarding medications, cosmetics, cleaning products, foods, drinks, and so many others. It is important for women to know that with anything they eat, take, or use – they are not harming their baby.
These are called “environmental factors”; environmental factors that can negatively affect fetal development are called teratogens. Teratology (study of teratogens) is derived from the Greek “teratos” meaning monster.
If an agent is deemed a possible teratogen, this indicates the agent has the capacity under certain conditions to produce abnormal development in an embryo or fetus, which can include physical, neurological, and developmental birth defects.
A major principle regarding whether an agent can be identified as a possible teratogen is that the agent should cause birth defects consistently across large studies, and the type of birth defect(s) should also be consistent across studies.
However, the study of teratogenicity of any agent is fraught with complications and can be very difficult to assess with complete certainty, especially when effects are either subtle or take years to develop (neurological/developmental).
It is important that pregnant women – and their partners/families – understand why research regarding teratogens (and pregnancy in general) is the way it is and what it means before beginning a dive for answers. HCPs do not know a lot of about the safety of environmental factors or how they affect pregnancy and it is important that pregnant women understand why (read Research and Pregnant Women).
The purpose of collecting and evaluating data on drugs, chemicals, heat, and even certain activities during pregnancy is to address whether exposure to a particular agent could increase the risk of birth defects above the background rate.
Approximately 2% to 5% of pregnancies are complicated by birth defects, of which more than 7,000 different types have been identified. The most common figure reported is 3% of all pregnancies, which is considered the “expected background rate”, and is used as comparison in research studies.
For example, in general, when a study evaluates the potential cause (i.e. medication) of any specific birth defect, researchers look to determine whether the amount of birth defects in that exposed group was higher or lower than the expected background rate of 3%.
If the rate is similar to 3%, the study will indicate that within that studied group, it cannot be determined if the medication caused any of the identified defects, as it is the same as would have been expected in an unexposed group (i.e. “due to chance”) – as long as the studied group was large enough.
Researchers do not know the cause of most birth defects; however, it is currently estimated that 2% to 10% of all birth defects may be caused by drugs, viruses, bacteria, chemicals, and environmental toxins.
Despite this, research regarding outside agents during pregnancy has been very slow, especially regarding medications, cosmetics, and chemicals, mostly due to how research during pregnancy is conducted.
For example, teratology itself is relatively new because until the 1940s, it was thought that embryos were protected from outside factors due to the placenta; however, the research community started learning only 80 years ago that certain agents could in fact pass through the placenta and negatively affect the fetus.
They also started recognizing that animal studies were also not good comparisons for human pregnancy.
Further, most of this initial recognition was not necessarily due to research, but from very obvious physical malformations occurring much higher than the expected rate in large numbers of women exposed to the same agent (see thalidomide, rubella, and diethylstilbestrol, below).
However, accomplishing research scenarios to identify less obvious effects is exceedingly difficult during pregnancy:
For example, a drug’s more subtle effects may need a larger pool of women. If a study only assesses 20 women and indicates those 20 women/babies experienced no adverse outcomes, this would be considered misleading. It is possible that a study group of 10,000 live births or more may be necessary to identify possible associations. Again, well-established research hurdles make this hard to accomplish.
Although only a small number of possible categories of teratogens have currently been identified, this list is growing.
Due to certain physiological aspects of pregnancy, transfer of certain pharmaceutical drugs and other agents can cross the placenta, thus adversely exposing the fetus to the agent.
Note: Of interest, based on this, researchers are also attempting to learn which medications or agents could pass the placenta and positively affect fetal development, especially in fetuses with certain treatable conditions.
However, the exact mechanisms by which drugs, chemicals, and other environmental factors disrupt embryonic development and cause miscarriage or birth defects is not known, which also hinders research.
For example, if a baby is born with a birth defect and the mother was exposed to medication X, it may not be known whether it was the medication, the disease or condition for which she took the medication, if the woman had any other type of exposure that could have played a role, or whether the birth defect would have occurred anyway, regardless of the medication exposure or her condition.
Whether an environmental agent causes abnormal development depends not only on the physical and chemical nature of the agent, but the potential exposure (dose, duration, frequency, route of exposure) and timing of exposure (stage of fetal development).
Human teratogens generally increase rates of very specific defects or spectrum of defects. This is because certain stages of embryonic development are more vulnerable to disruption than others and by those specific agents. If certain time windows have passed, it is unlikely that agent would produce the same effect(s).
Therefore, since the first trimester is the period when most organs are formed, most HCPs recommend certain drugs not be used to skip this vulnerable window and avoid any possible unknown adverse effects. Researchers also recognize that medications that are potentially unsafe in the first trimester could be much safer later in pregnancy.
For example, if a drug is potentially associated with the development of cleft palate, but the drug is taken after 10 to 12 weeks of pregnancy (after the palate has formed), then the drug cannot cause cleft palate in that particular pregnancy. However, it is still possible the drug could have a different negative effect later in gestation, or none at all.
As a more detailed example, thalidomide (see below) produces harmful physical birth defects with a 10 milligram dose taken prior to 6 weeks of pregnancy, but no structural defects at 10 weeks with the same 10 milligram dose.
Another example regarding timing and fetal development: exposure to potential teratogens during 3 to 4 weeks of pregnancy (fertilization and implantation) are assessed to either potentially cause miscarriage (not birth defects) or no issues at all, known as the "all-or-none" phenomenon.
This is because the first four weeks mainly involve the development of the amniotic sac, extraembryonic structures, and chorionic sac. Differentiation of specific cells and organs starts on the 29th day of gestation (approximately 4 weeks, 1 day).
Additionally, it is theorized the embryo may somehow correct itself from some harmful environmental exposure during this time. Therefore, the most vulnerable period during pregnancy is likely weeks 5 through 16 (months 2 through 4, and not months 1 through 3).
Weeks 16 through delivery are considered lower risk, and it is assessed that teratogen exposure during this time likely results in functional deficits to a particular organ system, rather than structural.
Further, the brain grows throughout the entirety of pregnancy, and could potentially be affected at any point. Thus, even though women pass the period of organogenesis by the second trimester, developmental or neurological effects may still occur from certain exposures (learn more about Fetal Development).
The list of known and suspected teratogens is growing. Although research is slow, we know a lot more than we did decades ago. Current known and suspected teratogens include:
Viruses: Cytomegalovirus, rubella virus, and viruses associated with smallpox, chickenpox, measles, herpes, and poliomyelitis may pass through the placenta and cause fetal infection. The first time this was documented was in 1941, in which it was determined rubella could produce severe birth defects such as cataracts, deafness, and cardiac defects.
Herpes: The acquisition of genital herpes during pregnancy has been associated with miscarriage, intrauterine growth restriction, and preterm labor. In rare cases, HSV can transfer to the fetus during pregnancy, known as a congenital infection, and is associated with severe consequences, to include microcephaly (abnormally small head), hepatosplenomegaly (enlargement of liver and spleen), and stillbirth (read Oral and Genital Herpes).
Bacteria: Microorganisms can potentially cross through the placenta and infect the fetus.
Syphilis: A woman who has syphilis while pregnant can transmit the infection to her baby at any point during pregnancy or delivery, known as congenital syphilis (CS). CS can occur if a woman has untreated syphilis prior to pregnancy or contracts syphilis during pregnancy. CS can cause miscarriage, stillbirth, preterm birth, low birth, and even newborn/infant death. CS in the United States (U.S.) has increased by over 260% since 2013 (read Syphilis).
Listeria: Listeriosis can cross the placenta and infect the fetus, with a prevalence estimated to be 8.6 in 100,000 live births. If the mother is infected, there is a 20% to 60% the infection will pass to the fetus, which has a neonatal fatality rate between 20% and 35%; infection earlier in pregnancy carries a higher risk of severe complications. Congenital infection could also lead to miscarriage, preterm labor, and neonatal meningitis (read Listeria).
Salmonella: Most salmonella infections during pregnancy do not affect the fetus and outcomes are similar to non-pregnant individuals. However, in severe, systemic cases, salmonella infection during pregnancy can result in the spread of the infection to the fetus.
Salmonella bacteria has been identified in amniotic fluid and documented cases of an infected newborn have been reported. Consequences of infection during pregnancy can cause pregnancy loss, preterm labor, and stillbirth. However, early diagnosis and treatment is associated with a good pregnancy outcome (read Salmonella).
Toxoplasmosis: Congenital toxoplasmosis is a serious parasitic infection during pregnancy that causes miscarriage, as well as neurologic or ocular (eye) disease, and heart and brain anomalies in the fetus (pregnant women tend to be asymptomatic).
To prevent infection, pregnant women are asked to avoid cat litter boxes as cats can excrete T. gondii eggs that can then infect humans; women are also advised to avoid food, water, and soil that may have been in contact with cat feces. Note: Pet cats that are kept indoors and only provided with cooked, preserved, or dry food are less likely to cause infection (but infection is still possible).
The prevalence of the infection is unknown as it is not a reportable condition; further, it is not routinely screened for in pregnant women, despite its potential consequences. Further, some of the visual, developmental, and neurological effects may not affect the child until years later.
The best method of prevention is for women to avoid changing cat litter, but if they need to, they should use gloves and wash their hands afterward.
Toxoplasmosis can also occur through consumption of contaminated fruits and vegetables and improperly cooked meat (read Food Safety).
Alcohol: Based on what science currently understands about embryology, fetal growth and development, and the breakdown of alcohol, every ounce of alcohol affects the fetus. Therefore, no amount of alcohol is safe during pregnancy. Alcohol’s most well-known effects on a fetus are physical – mostly affecting head and face development. However, alcohol also negatively influences the brain, which grows the entirety of pregnancy.
Alcohol can cross the placental barrier into the fetal bloodstream and amniotic fluid; further, the fetal liver is not mature enough to convert/metabolize the alcohol; it is also one of the last organs to fully develop.
Therefore, the fetus’ blood alcohol content is not only the same as the mother’s, but alcohol remains in the fetal system for much longer. Further, when the fetus urinates into the amniotic fluid, it creates the possibility the fetus will either swallow the alcohol or “breathe” its breakdown components into the liquid-filled lungs (read Alcohol).
Fever: Currently, fever is a suspected teratogen, but significantly more research is necessary. While it does appear that a high, prolonged fever during pregnancy may be associated with fetal physical and development defects, especially during the first trimester, there are many factors to consider and women should not panic if they get a fever during pregnancy.
Results regarding fever’s effects during pregnancy are very inconsistent and incomplete. The impact of a woman’s fever on her pregnancy depends on the fever itself, when the fever occurs and for how long, the illness causing the fever, and whether the woman takes steps to adequately manage the fever and/or seeks treatment for the underlying illness (read Fever).
Heat: Concern regarding the use of hot tubs, saunas, hot climate, and lengthy hot showers and baths is due to research showing harmful effects in the general population as well as pregnant animals from prolonged heat exposure. However, “prolonged” exposure is not defined, and the minimum core body temperature at which damage may begin is not known (research is similar to fever) (read Heat Exposure).
Illicit Drugs: Use of illicit drugs like cocaine and opioids during pregnancy can cause serious problems for the mother, fetus, and newborn. Cocaine readily crosses the placenta, which constricts blood vessels, reduces blood flow, and restricts growth. In general, these drugs can cause placental problems, birth defects, fetal growth restriction, and preterm birth.
Women who used these drugs prior to pregnancy or who are currently abusing opioids or other prescription medications during pregnancy should talk to their HCP without fear of recourse. Resources to help women quit substance abuse can be found here.
Lead: Even low lead exposure during pregnancy is a serious concern, as it can cause neurotoxicity, developmental delays, and low birth weight in the newborn, as well as potential miscarriage. Interestingly, lead exposure can cause problems during a pregnancy even when a woman was exposed to lead years prior, but not actually during her current pregnancy.
This is due to the transfer of lead stores in the mother’s skeletal system to the fetus during pregnancy. Women who believe they may be exposed to lead (from their home or occupation) or who were exposed to lead previously (before pregnancy) should inform their HCP.
Marijuana: The THC molecule in marijuana combines very well with fats and is distributed rapidly to the brain and fat of the fetus after ingestion or inhalation by a pregnant woman. When a pregnant woman consumes marijuana, it is estimated the THC in fetal blood may be about 10% to 33% of the mother’s blood levels; this can change based on amount and potency.
Adverse fetal effects as a result of THC exposure is also highly dependent on the stage of pregnancy. Exposures during initial stages are associated with increases in pregnancy loss and birth defects; exposures in mid-gestation could lead to fetal growth restriction.
In addition to THC, there are several harmful chemicals present in marijuana smoke including nitrous oxide (NO), oxides of nitrogen (NOx), carbon monoxide (five times higher than tobacco), hydrogen cyanide, aromatic amines, ammonia, toluene, benzene, and polycyclic aromatic hydrocarbons – all of which present their own adverse effects (read Marijuana).
Methylmercury: Mercury is a metal that occurs naturally in the environment, accumulating in the aquatic food chain (seafood) as methylmercury (mercury). Exposure can occur through touch, inhalation, or consumption.
Evidence of acute effects on the developing fetus were first seen following an industrial disaster in Japan in the 1950s when mercury spilled into a local bay. Pregnant women who consumed the contaminated seafood had a high prevalence of fetal neurotoxicity and abnormalities involving the central nervous system.
Mercury readily crosses the placenta and fetal levels have been found to be greater than maternal levels (read Seafood for more information, to include dietary recommendations). Seafood is safe and beneficial during pregnancy as long as certain factors are taken into consideration.
Radiation: Radiation is a type of energy that travels as rays or particles in the air. When used for medical imaging, these rays are used to pass through the body to create an image. Radiation exposure during pregnancy has been associated with adverse outcomes to include prenatal death, intrauterine growth restriction, small head size, mental disabilities, birth defects, and childhood cancer.
However, not all types of imaging expose the fetus to the same dose or in the same way. Radiation risks throughout pregnancy are related to the stage of pregnancy, the absorbed dose, the amount of tissue the x-ray beam must penetrate, the direction of the projection, the depth of the embryo/fetus from the skin surface, x-ray technique factors, and lead shielding.
Further, some imaging techniques that use radiation (CT scan, x-ray) during pregnancy may be necessary for the health of the mother; therefore, in some cases, the diagnostic information may be of significant benefit compared to the minimal assessed risk (read Radiation).
Tobacco Smoke/Nicotine: Nicotine travels from the mother to the fetus, affecting the developing brain and lungs, leading to potential neurological and pulmonary problems after birth. Tobacco smoke and its chemical make-up can affect gene regulation, decrease folic acid, and cause inflammation in the body – increasing the risk of complications such as miscarriage, ectopic pregnancy, fetal growth restriction, various birth defects, preterm labor, and even stillbirth (read Smoking).
Vaping: E-cigarettes contain dozens of chemicals that have yet to be studied in humans, let alone during pregnancy. However, while there are more than 7,000 different flavors available, the main chemicals in these solutions have only been studied regarding oral ingestion, and not inhalation.
Further, nicotine is only one of numerous different identified chemicals in e-vapor; it is already known to be neurologically toxic to a fetus, and it is assessed that pregnant women may receive higher amounts of nicotine through the use of e-cigarettes than traditional cigarettes (read Vaping).
Researchers learned a lot about the teratogenicity of medications after the thalidomide and diethylstilbestrol disasters.
Thalidomide is one of the most famous teratogenic agents from the last 70 years. Originally prescribed in Europe for nausea and vomiting of pregnancy (“morning sickness”) in the 1950s, it was found to be a potent teratogen that caused primarily limb defects in the babies of the mothers who took the medication, as well as issues in almost every other organ system.
There are currently more than 20 hypotheses of how the drug disrupted development/caused these defects. It is no longer prescribed during pregnancy (since 1961), but its current use for other medical reasons is increasing (leprosy, multiple myeloma).
It is currently estimated the drug caused birth defects in over 10,000 children, mostly in Europe. The drug was never approved or officially given to pregnant women in the U.S. (some women in the U.S. were still exposed to the medication).
Regardless, drug testing in the U.S. completely changed after this tragedy, which indicated for the first time that pregnant animal studies (which showed it to be safe) cannot always be extrapolated to pregnant humans.
Diethylstilbestrol: Diethylstilbestrol (DES) is an estrogen drug previously prescribed to pregnant women from 1938 to 1971 to prevent miscarriage. Research later showed that it could potentially be a carcinogen or even a teratogen. Female fetuses who were exposed to this drug were determined to have a high risk for clear cell adenocarcinoma of the vagina and cervix as young girls or adults; male fetuses were also shown to have structural anomalies in the genital tract during adulthood.
Anticoagulants: Anticoagulants are known teratogens during pregnancy; this is a very complex and challenging issue, as these medications may be necessary for certain pregnant women to prevent venous thromboembolic events (deep vein thrombosis, pulmonary embolism) and as well as complications from other conditions.
Anticoagulants have been shown to cause harm in animal embryos early in pregnancy; however, in humans, effects can be unpredictable and are most likely dose dependent (the lower the dose, the lower the risk). Adverse effects in the fetus may include brain hemorrhage and nasal hypoplasia. Although low molecular weight heparins may carry the lowest risk, women may be advised to avoid these drugs during the first trimester and the last several weeks before possible delivery.
Women who are currently on these medications or need these medications during pregnancy will need to have a detailed risks and benefits discussion with their HCP. Women should ask as many questions as they need to feel comfortable and confident with their decision. Women should also read Venous Thromboembolism and Vitamin K for more information.
Anticonvulsants: Approximately 1 in 200 pregnant women is epileptic and requires treatment with an anticonvulsant; these medications are also used to treat neuropathic pain, migraine headaches, and psychiatric disorders.
Although study sizes are small, these medications (such as valproic acid) may cause neural tube and facial defects, as well as intrauterine growth restriction, cognitive dysfunction, low IQ, microcephaly, and possible infant death.
As mentioned above, women who are currently on these medications or need these medications during pregnancy should have a detailed risks and benefits discussion with their HCP. This is important, as women also need to consider the risks of not taking these medications.
Oral Contraceptives: Although DES is a hormonal drug, the teratogenicity of oral contraceptives is not clear. Oral contraceptives taken during the early stages of an unrecognized pregnancy are suspected of being teratogenic, but this remains inconclusive and not all studies have determined accidental exposure to be harmful.
However, contraceptives should be stopped as soon as pregnancy is suspected or confirmed. Women who were taking contraceptive pills before learning they were pregnant should not be concerned but should still inform their HCP.
Retinoids are a form of Vitamin A that include the active substances acitretin, adapalene, alitretinoin, bexarotene, isotretinoin, tazarotene and tretinoin (Vitamin A through food is not toxic). They are taken by mouth or applied as creams or gels to treat several conditions mainly affecting the skin, including severe acne and psoriasis. Some retinoids are also used to treat certain forms of cancer.
Oral retinoids can cause depression and suicidal thoughts in women who take it, as well as birth defects when taken during pregnancy; therefore, retinoids are absolutely contraindicated (not recommended/complete avoidance) for women who are pregnant or considering pregnancy. Although not every baby exposed to oral retinoids during prenatal life is born with a birth defect, the risks are very high (20% to 60% of all fetuses exposed).
Oral or topical retinoid medications can include (but are not limited to) the following brand names:
Isotretinoin (Acutane®, Zenatane®, Absorica®, Claravis®, Amnesteem®, Myorisan®)
Tazarotene (Fabior®, Tazorac®, and Avage®)
Tretinoin (Retin-A Micro®, Refissa®, Retin-A Micro Pump®, Tretin-X®, Atralin®, Renova®, Retin-A®, and Avita®)
Although topical versions of retinoids have not been shown to produce the same detrimental effects as oral retinoids, most HCPs advise against topical versions of these medications as well as an act of caution. However, sporadic cases of ear, eye, and central nervous system malformations have been reported with topical use (read Acne).
Tetracyclines (which include minocycline, doxycycline, and tetracycline) are commonly used in the general population for the treatment of acne but are not recommended during pregnancy. Tetracyclines can case fetal malformations as well as deposits that discolor fetal bones and developing teeth; they may also cause liver concerns in women. However, there is currently very little evidence that these fetal concerns occur with tetracycline use during the first trimester. The exact point in pregnancy where tetracycline begins to cause harm is unknown.
Additional specific medications to be avoided (contraindicated) during pregnancy due to evidence of fetal harm (Note: women should always call their HCP first before stopping any medication regimen):
Ethisterone, norethisterone, and megestrol
As soon as women find out they are pregnant, or are considering getting pregnant, they should call their HCP and discuss:
Their current medications
Possible exposures to lead, mercury, and other heavy metals
Any history or current use of tobacco, nicotine, alcohol, or marijuana
Any history or current use of illicit drugs such as cocaine, heroin, and methamphetamine
Any possibility of a current bacterial, viral, or fungal infection
For women who are required to take regular medication and find out they are pregnant, they should call their HCP as soon as possible. Some medications may need to be stopped or changed immediately upon pregnancy, and some women may not have their first appointment until 6 or 8 weeks. Women can simply call their HCP and leave a message to discuss their medications.
Women should also remember, however, that not all medications are considered unsafe and may be necessary; they should not stop any medication unless they have spoken with their HCP.
Women should also be forthcoming to their HCP about any potential illicit drug use either prior or during their pregnancies. HCPs can help women find support and resources necessary to quit.
While not all birth defects can be prevented, women can take steps to increase the chance of having a healthy baby. Women should:
Take care of medical conditions before pregnancy.
See a healthcare professional regularly.
Take prenatal vitamins.
Get 400 micrograms of folic acid every day.
Maintain a healthy weight.
Ask an HCP to measure thyroid hormone levels at the first appointment.
Speak to an HCP regarding any and all medications (to include over-the-counter and herbal).
Prevent infection and learn to recognize infection.
Switch their regularly used salt source to iodized table salt (instead of pink/Himalayan, kosher, sea salt)
Follow HCP guidance regarding vaccinations.
Treating for Two: Medicines and Pregnancy (U.S. Centers for Disease Control and Prevention)
Medicine and Pregnancy (U.S. Food and Drug Administration)
Teratogen Information System (University of Washington)
MotherToBaby (Organization of Teratology Information Specialists)
Prescribing medicines in pregnancy database (Australian Government Department of Health)
Drugs and Lactation Database (LactMed)
Thalidomide‐induced teratogenesis: History and mechanisms (Birth Defects Res C Embryo Today. 2015 Jun)
Preventing Congenital Toxoplasmosis (U.S. Centers for Disease Control and Prevention)
Netflix documentary called "Attacking the Devil" (2014) which is based on the journalistic aspect of the Thalidomide disaster in the U.K.