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#160 Sura Alwan on Teratogens

by Kira Dineen
October 29th 2021

Joining us this episode is Dr. Sura Alwan, the Co-Director of TERIS, The Teratogen Information System, a clinical resource that assesses teratogenic risks of ... More

How is it that we find ourselves surrounded by such complexity? Such elements jeans, you and me are all made of DNA were all made of the same. Hello, you're listening or watching DNA. Today we are a genetics podcast and radio show. I'm your host, Kristine. I'm a prenatal genetic counselor and on this show we explore genetics and the impact on our health with conversations of leaders in the field. My guest today is Dr Cheryl Lynn who is the co director of Terrace, the travel agent information System, which is a clinical resource that assesses telegenic risk of pregnancy exposures on the fetus. A little bit about DR Alwyn, she has a birth defects epidemiologists and tear it. Ologists who hold professional positions at the university of Washington and the University of british Columbia.

Do you or someone you know have Prader Willi syndrome? Harmony Biosciences. Looking for people with Prader Willi syndrome to enroll in a new clinical study in the United States. Harmony Biosciences will be studying the safety and impact of an investigational medicine on excessive daytime sleepiness, cognition and behavioral function in people with Prader Willi syndrome. Use the link in the show notes to learn more about the clinical study and refer a patient to a study center. The link is also available at DNA podcast dot com Picture genetics is unique. DNA testing service with test designed for every stage of life, including family planning with a picture parenting carrier test, you can uncover genetic conditions that may be passed on to your kids such as cystic fibrosis or fragile X syndrome. Unlike other companies, this is actually a clinical grade test where physicians and genetic counselors are involved. It's easy to order and understand with good looking reports to order your picture genetics test. Go to picture genetics.com and use code DNA today for 25% off and free shipping.

Get actionable genetic insights today to benefit your family of tomorrow. Thank you so much. Dr Elwyn for joining me on the show today. My pleasure. So, I thought we could start out with some background information on birth defects for those that maybe you've heard of birth defects but don't understand their causes, possibly preventions from that. Could you provide our listeners with a little bit of background on this? Absolutely. So, um birth defects um what we commonly refer to as congenital congenital anomalies um can be structural or functional abnormalities that occur during intrauterine life. Um structural birth defects or malformations are seen in about one in 33 infants within the first year of life and are considered the second most common cause of infant mortality after prematurity. So, the accounts for up to 25% of all perinatal deaths. The frequency of structural birth defects is higher, usually in spontaneous abortions or miscarriages than a live born infants reflecting that many of the most severe conditions are incompatible with survival, functional uh congenital anomalies or birth defects like intellectual disability are infrequently recognized an embassy but are at least as common as malformations among older Children and adults in terms of causes genetic factors including chromosomal abnormalities and single gene conditions probably cause about half of all recognized birth defects, While environmental factors account for up to 5%.

Um And there's also the combination of both multiple genetic and environmental factors what we call multifactorial causes um that are thought to produce the remaining and um with regard to prevention um while understanding the potential causes of a child born with a birth defect, whether it's genetic, multifactorial uh estrogenic exposure that has been identified would lead to more appropriate management and counseling for future pregnancies and would provide the families with an opportunity to make future productive decisions but are better for them of course. Primary prevention uh would be the would eliminate tremendous suffering and costs. So um with that I mean including optimizing women's health before conception by um uh screening and treating illnesses, avoiding cigarette smoking or abuse of alcohol or other recreational drugs and achieving a healthy body weight by getting sufficient exercise and a healthy diet and taking folic acid um prior to conception along with other essential vitamins and traditions can have a role in the development of birth defects.

What are some of the more common terror genetic exposures. I mean you mentioned a couple of them in terms of like cigarettes, um alcohol exposure, different medications. Are there any others to throw into the mix. Um Yeah so let me begin by um by defining strategy because sometimes that is probably a term that is not um it's not very common to hear, I agree with. Um Yeah so um generally the term to religion has been used to denote an agent that can cause um abnormalities of form function or both in an exposed embryo or fetus. And this could be a little misleading because it denotes that any agent is either a strategy or not a strategy. So we always uh commonly think of a list of human strategy since um uh that we want to avoid and a list of safe medications or exposures that are okay to take to be um to be exposed to in pregnancy. And reality strategy necessity is actually a property of an exposure which doesn't only include the physical or chemical property of the agent but also those the route um Gestational timing involved.

And there are also other factors that would determine whether an exposure can cause developmental damage. Such as um other concurrent exposures or genetic susceptibility of the mother and the embryo or the fetus to to this particular exposure. Um So um you asked me if estrogenic agents um uh what what what what kind of cryogenic exposures um um We know so um I want to I want to move on to say more like the transgenic exposures can be grouped into four major categories on the basis of the kind of agent involved. Um We could have infectious agents um such as viral infections like uh ra Bella and zika for example, um or parasites like toxoplasmosis. Um They could be physical agents like ionizing radiation, X rays, for example, or heat. So possible sources of feudal hypo hypothermia include high maternal fever during the very early stages of pregnancy, um that may predispose to the development of neural tube defects, for example.

And another type of estrogenic agents are the drug and chemical agents and those include environmental agents like organic mercury compounds, for example. Food that is heavily contaminated with methylmercury um can affect um the normal development of the central nervous system and is considered a transgenic exposure lead also is another example recreationally substances such as alcohol and tobacco use. And uh those ones stand out because they are considered important public health problems in our society and for both adults and the developing embryo or fetus. Um Also prescription drugs, um examples of those include uh um salado might um some uh it's a known example uh and then some anticonvulsant drugs um like well pro casted um retinoic acid, which is has been treated for acne. These are all considered to be pretty cryogenic and the fourth type of transgenic exposures are what we call maternal metabolic factors like inadequate intake of folic acid, um obesity or being diabetic and they so diabetes mellitus is actually considered the principal maternal metabolic disorder that raises concern for the developing fetus And focusing in on some of the medications that pregnant people are taking.

I mean, it's estimated 90% of pregnant people are taking some medication at some point during their pregnancy. So that's most people. What are some of those common medications that it's okay to take during pregnancy? Okay, so um it's important to know that medications in general are not tested for safety and human pregnancy before they are approved for marketing. Um because of ethical reasons for that. But um the passive adverse event reporting schemes that required after their approval have proven to be inefficient means of identifying drug treatments that may cause birth defects. So one of the most difficult aspects of counseling pregnant women about transgenic risks associated with various exposures during pregnancy is the fact that there are very few exposures for which the available information is sufficient to estimate the magnitude and the severity of the risk with any confidence. And when we talk about medications available data are pretty insufficient to determine the estrogenic risk associated with medications that um pregnant women may be treated with.

So I think it's important for health care professionals to admit um the limitation of their knowledge to the to themselves and to their patients as well. And the risk should be provided as an estimate um and couched in appropriate uncertainty as well. This may be inconvenient, but it is also better than assuming that the lack of information. I mean the lack of risk or vice versa. Yeah, I think that's really important just to share with patients. This is the research that we have so far. We haven't seen any adverse reactions or development birth defects in a developing fetus when taken during pregnancy, but research has never full proof. So certainly that's an aspect to be highlighting to patients of, okay, this is all the information. Yeah. You know, thinking about certain prescriptions. Antidepressants are very common. So Lexapro, Zoloft, PROzac, Just to name a few. These are more heavily studied compared to other medications that we've been talking about. The recommendation for pregnant people that are on these medications prior to getting pregnant and maybe just found out there, whatever, six weeks pregnant, they're like, okay, I just discovered this.

Do I continue my antidepressant, um what's the, the general advice or conversation surrounding that? Yeah, that's a great question because um the examples of antidepressant drugs that you mentioned as well, um all belong to a class of drugs called selective serotonin re uptake inhibitors or SS arise for short and these medications are the most commonly used antidepressants nowadays among women of reproductive age. Um they're probably the most commonly used prescription medications in general. Yeah, so because of that, there's been an extensive amount of studies assessing the strategic risk of these medications and pregnancy. And although there have been a small number of studies that have shown the risk of birth defects. Um Specifically heart defect to be slightly increased um over the background risk background population risk of 3-5%. The majority of the studies did not detect that increased risk um in terms of taking. So uh for for most, for most of the ss arise.

But in terms of taking those drugs later in the second or third trimester of pregnancy, it appears to contribute to uh some pregnancy complications, such as low birth weight or preterm delivery, and some withdrawal symptoms when taking uh late in pregnancy, uh neonatal withdrawal symptoms. Um But research has also shown that untreated anxiety or depression um could also increase the chance of such pregnancy complications. So, it's very difficult for most of most of these studies to determine whether those risks are actually attributable to the medication or to the underlying condition or to other factors that are common between the both. So it's important to focus more on assessing the individual needs for each pregnant women battling depression by providing comprehensive counseling and support with all treatment options discussed on a case by case basis. Yeah, I think that's really important just to look at, okay, there could be some risk being on a medication, but on the flip side, there also could be risk of not taking that medication.

I think you highlighted a really important aspect that a lot of pregnant people may not be realizing of, oh, there's risk if I'm not on this medication and anxiety. Depression during pregnancy can have an effect as well. Um So really looking at the person um and you know, the individual and coming at it from more of that holistic angle. Another question that I get from patients probably every day now that we're in this pandemic is what do we know about COVID-19 and pregnancy. Have there been any findings on effects to a fetus if a pregnant person contracts covid 19? Um And then along with that as vaccinations should pregnant people be vaccinated? Yeah. So um you know, information on COVID-19 is rapidly evolving. But in terms of early pregnancy exposure, there's not enough data yet for us to determine any strategy nick risk with confidence. But available studies so far do not suggest an increased risk of either miscarriage or birth defects. Um It's important to note however, that, you know, fever is a symptom of COVID-19 and as I mentioned earlier that elevated maternal temperatures in early pregnancy could interfere with central nervous system development.

Um In terms of exposure throughout pregnancy in general and the risk of other pregnancy complications. It seems that infection with COVID-19 and pregnancy increases the chance for preterm delivery. This has been shown in plenty of studies. Big Studies and some studies have also shown increased risk for preeclampsia which is um means severe pregnancy hypertension or high blood pressure. Um and low birth weight. Uh and also um the majority of them affected pregnant women who uh um get infected with COVID-19 end up having um delivering c. section. So again this all depends on how severely affected the pregnant patient is and how sick she is. Um And and the timing of exposure of infections Um in terms of the COVID-19 vaccines. Um well they're not like vaccines and based on what is known about these types of vaccines getting a Covid vaccine is not expected to increase the chance of birth defects. Of course there's no studies um yet but um pregnant women are now who are taking the vaccine are being enrolled in clinical trials and hopefully though we'll have more data to be able to um um confirmed safety of this up taking the medication after.

Sorry of taking the vaccine in pregnancy. Yeah. And even with the COVID-19 vaccine, it's also looking at from the other side is if you don't get vaccinated during pregnancy, what is the risk of having you know, COVID during pregnancy? And we've seen that that cases of covid 19 during pregnancy, those tend to be more the severe cases um during pregnancy, the immune system is lower. So that's certainly part of, you know, the deciding whether to get vaccinated or not. And certainly talk to health care providers and helping to make that um decision. But right now I think the big highlight is we've not seen any birth defects related to the vaccine or the virus in general. That's correct. Yeah. And the other exposure I wanted to talk about briefly is marijuana. This is one that a lot of people are using and there's think limited information in terms of the effect on a pregnancy. Is is there any concrete data? Is there any recommendations If someone is obviously we want to say that we want to avoid recreational drugs during pregnancy, but some people are going to regardless.

Is there any advice coming from your standpoint with that? So the problem that the effect of marijuana use during pregnancy is very difficult to estimate or study Um marijuana or cannabis um contains about 400 different chemicals and preparations uh also differ between you know, place in place and and can be contaminated with other drugs with pesticides or um other stuff. So although the majority of studies um do not indicate an increased risk of birth defects among women who took marijuana and early pregnancy, those studies are older nature. And um the THC the main component in marijuana um that was available that is available today is uh is stronger and it's far more potent um than before. And also um The routes of exposure have changed. So most women used to inhale and now it's become more edible and uh edible marijuana might have might lead to higher levels in the body and possibly a higher risk to the fetus.

So the general recommendation is treat from marijuana like alcohol and try and avoid during pregnancy as much as possible. It's really not known what the risks could be. If you have patients with Prader Willi syndrome, please let them know about a new clinical study. Looking for participants across the United States. Harmony Biosciences will be studying the safety and impact of an investigational medicine. The study will focus on excessive daytime sleepiness, cognition and behavioral function in people with Prader Willi syndrome. The study participation is four months long and consist of five visits. If you're patient at your visits, you will participate in sleep tests and have general check ins on how you're feeling. You'll also need to keep a sleep diary for the first two weeks in a closing diary. Once you start treatment, if you're a caregiver, you'll attend all visits with the patient and help provide information to the trial researchers. There are 13 trial sites in the United States and Harmony Biosciences will reimburse patients to travel to their closest site, refer yourself a patient or a loved one to the study by visiting the link in the show notes, which is also available at DNA podcast dot com.

To remind you about picture genetics with their exclusive 25% discount for you as a DNA. Today listener picture genetics is different from a traditional direct consumer test because it's clinical grade testing with every case reviewed by a health care provider. Results are focused on health with medically actual and useful information for you and your family. I did a couple of their kits including their picture parenting one. Here's how it worked. I sent off my tube spits the lab who sequenced a bunch of genes. This means that they've read through each gene to see if there was a mutation or pathogenic variants as we genetic counselors call them. Then a geneticist looked at my results and created a beautifully easy to read report, informing me about my carrier results. Here's my favorite part. There's also genetic counseling offered. So you can speak with a genetic counselor about your results. Order your own kit at picture genetics dot com and use code DNA today for 25% off and free shipping again. That's picture genetics dot com get actual genetic insights today to benefit your family of tomorrow.

There's a lot to keep track of during pregnancy for people that are pregnant, looking to get pregnant. But also health care providers to track all the new research with all of the traditions and Okay, what is the recommendation? How dangerous is this at what point in pregnancy? Is it dangerous? You're the co director of terrorists. Could you give us a bit of a background on the database and how this could help health care providers stay updated on this. I mean, I'm included in this list of practicing prenatal genetic counseling. Absolutely. So terrorists. Um, Which stands for the tradition information system. It's an authoritative dynamic clinical dermatology resource located at the University of Washington. That provides expert guidance on the cryogenic risk of over 1700 medications and other exposures, including infections and vaccines. and terrace was founded in 1984 by Dr. Jan Friedman, who is a clinical geneticist and the a clinical psychologist and a professor of medical genetics at the University of british Columbia.

Um so dr Freedman colette the database um as its principal investigator along with dr Janine politica who served as terrorist director until december 2019. And together they wrote an updated the summaries for all this time. Um and terrorists wouldn't have been there without them. Um And Dr Friedman continues to hold a key role in terrorist as an advisory board member. So who else is part of the team to create all these summaries for all the different religions. I mean, you have over 1700. That's that's a huge database. I mean, that's like you know, you think about the most common medications, that's usually like 100, But you go way beyond that. That's right. Um So um We have um as of January 2020 terrorists um um agent summaries are written and updated by myself and my co worker Dr Kimberly Grant, who co directs terrorists with me. Dr Grant is a developmental neuro toxicologists in the department of Environmental and occupational health sciences at the university of Washington.

Um Our current uh principal investigator is dr tom burr Becker who is a professor in the department of environmental and occupational health sciences at U. W. As well. Um Terrace is also supported by our wonderful program administrator, uh jenny Yang. And the risk ratings in Terrace are specifically vetted by an advisory board of eight world experts in clinical tear it ology. Uh We meet twice a year either in person um at our annual meeting of the Society of Birth defects and prevention or over video conferencing which has been the case lately. Um And uh we review all the updated summaries and engage in discussions and get a group consensus from the uh from the group from the from the board on the risk ratings. So I'd like to mention who was on our board because it's a feature that we are very lucky to have on terrorism and distinguishes terrorists from other resources on our board. We have dr Jan Friedman, who is the founder of terrorists. I mentioned him earlier.

We have dr ken jones who is the world renowned archaeologist and tear it ologists. He's considered the leading expert of fetal alcohol syndrome As he was one of the two doctors at um U. W. who first identified uh fetal alcohol syndrome in the United States in 1973. So we are also fortunate to have dr Rich Miller, he's a senior pharmacologist and toxicologist and dermatology expert from the University of Rochester medical center and dr Margaret Adams. Our clinical geneticist from UW. Also on our board. We have four senior perinatal epidemiologist. Dr Christina Chambers from U. C. S. D. Dr Sonia Hernandez Diaz from Harvard School of Public Health, Doctor Cheryl Broussard from the division of uh birth defects and infant disorders at C. D. C. And dr Garry shaw from Stanford University. So it really takes a team to be able to review all the literature, all the studies and come up with these very easy short summaries.

What are some of the information that health care providers can access in the summaries? And we're going to include an example on the website but just for a preview for people what information is included in the breakdown. Um So um as you know, um let's see uh clinical assessment of human transgenic risk requires careful interpretation of data obtained from several kinds of human studies as well as animal studies. So in terrace analysis of each agent strategy, ethnicity has been made on the basis of um it's reproducibility, consistency and biological plausibility or available data or of available clinical epidemiological and experimental data. And the reproducibility is considered to be particularly important if this is the study of the studies are of different design and if the types of anomalies observed in various studies are consistent. So um um near the beginning you want to know what information is available in terrorist.

So near the beginning of each agent summary would be and what we call an aphorism printed clearly or entirely in capital letters. And it rates the risks and the quality of data available upon which the risk rating has been determined. This aphorism was rates the risk of transgenic effects and the Children of women exposed to the agent during pregnancy as either none, minimal, small, moderate high, undetermined or unlikely. In some instances this rating is amplified by a comment. For example, an agent may be rated as undetermined with a comment that says a small risk cannot be excluded, but there is no indication that the risk of congenital anomalies and the Children of women treated with this agent during pregnancy is likely to be great. And similarly the risk of transgenic effects may be may be rated as unlikely um with a comment that says unlikely to pose a substantial strategic risk with usual exposures just to make it clearer what it means. Um So to conclude uh so you so so you wouldn't conclude that there's absolutely no risk.

Um So and such statements are made specifically on the basis of general pharmacology, animal data or or analogy too closely related agents that have been more thoroughly studied then. Um um The aphorism also rates the available data, so which right below the risk rating there is a quality of data and those are based as none LTD fair, good or excellent and risk assessments based on the evidence that is limited or fair ought to be considered tentative uh and may change as more information would be available for that agent. Um And so proceeding all of this is a brief discussion of the data upon which it is based? Uh some emphasis has been placed primarily on information obtained from human studies and experimental animal studies are also included to amplify and clarify the analysis, but in general all the experiments and mammals are considered. Um and the references we have at the end included in the age of summaries have been selected for their quality and accessibility.

Um These references are not intended to provide a comprehensive bibliography but rather to help the clinician obtain a broader understanding of the agents effects on the embryo and a fetus. So we provide free summaries as well. If you go to our website, we provide free summaries, a sample summaries and the covid related summaries are all available for free all the time because of its need. So we have covid agents, we have the medication, the vaccines associated um and that are updated on a regular basis of every three months. And how can people subscribe and access the information that's not included in that free. You know, it's it's fantastic. You're offering the COVID resources that are free because that's so important right now for all health care providers to know. Um if they're looking to access some of the other drug summaries. I mean you have over 1700. So all of those how can they subscribe to terrorists. Um So when you visit our website at D. O. A. Chess dot Washington dot e.

D. U slash terrorists. It's a long website because it's affiliated with the university, but you can simply google terrorist University of Washington and you'll get there. Um So subscriptions there you go to subscribe now and you'll find that we have a list of licenses that you could choose from. Um subscriptions there are for individual use. Um and you can also there's life, there's a license for clinical use that involves 2-4 practitioners. There is also another license for uh you know, for 10 investigators or more to use terrorists under one license. Um and there are also large volume licensing, such as for pharmaceutical companies, uh medical centers or universities which are also available. We uh provide uh an evaluation license for um for uh 15 days, which is for free to members of the National Society of Genetic counselors and would like to extend that as well to D. N.

A. Uh today uh subscribers or listeners. So uh so another thing we provide is an academic license that is also at no charge provided to medical students and medical residents until the end of the program. So all of these press subscriptions are managed by the commotion Innovation Center at the university of Washington. Anything else to add before we end? Uh while there are several sources of information available on the safety of drug exposures during pregnancy terrorists is unique in that it is governed by an advisory board of global authorities and clinical pathology from the fields of medicine, epidemiology and genetics. And the advisory board carefully reviews all agent summaries, anthropogenic risk ratings are generated by group consensus. This makes the level of clinical authority on the strategic risks provided by terrorists unmatched in the world. Also, unlike other transgenic risk databases, terraces and academic resource located to the school of public health at the University of Washington, which is ranked 4th in the world. The terrorist databases considered an intellectual property of the University of Washington, visit terrorist today via the link in the show notes.

Also available at DNA podcast dot com and use Codina today for your free no obligation, two week evaluation license. And you connect with us on social media search DNA Today on all the social media places. Any questions for myself or Doctor Alwyn can be sent in to info at D. N. A podcast dot com. Thanks for listening and watching. You can join us next time to learn discover new advances in the world of genetics and DNA. We're all made of the same chemical. DNA. We're all made of being a

#160 Sura Alwan on Teratogens
#160 Sura Alwan on Teratogens
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