Hello, everyone. I think it's two minutes after 11, so I'll probably have to start. So my name is Marina, and I am really delighted to have this opportunity to talk to you about the topic that I'm really interested in. I started teaching occupational hazards and pregnancy to occupational medicine residents a few years ago. And the reason why I started, because there was a gap in our academic curriculum. And I'm sort of, over the years, I'm realizing that there is somewhat of a gap, I think, in general, in occupational medicine, because I think this topic is somewhat less, it's somewhat overlooked or probably understudied compared to some other areas in occupational medicine. So it's a huge topic, and of course I will not be able to cover it all, so I'll just mention some select subtopics. So this is my disclosure slide. So the outline. I will start by talking about the general principles of how reproductive hazards can lead to adverse outcomes. And I will talk a little bit about the paradigm shift and increasing understanding of the role of epigenome in the development, and also in the development of negative outcomes. I will use arsenic as an example of a reproductive toxicant, which has multiple effects, including epigenetic effects. And the reason why I'm using arsenic is because it's a little bit better studied than some other toxicants when it comes to molecular understanding of how it changes the epigenome. I will mention endocrine disruptors, and then the second part of the talk, I will cover select hazards with so-called critical windows during the pregnancy. So I will mention varicella, parvovirus B19, heat, shift work, noise, ergonomic hazards, and I will finish by talking about the positive effects of exercise in pregnancy. So when we think about the endpoints during pregnancy, they can be divided into reproductive and developmental. And just to remind you, when we say reproductive, these are the outcomes that affect the mother. So the reproductive system of the mother, such as infertility, time to conception, effects on menstrual cycle length, age at puberty, or menopause. And on the other hand, developmental hazards are the ones that affect the fetus. So these could include spontaneous abortion, effects on fetal growth, various congenital malformations, abnormal organ function, and interestingly, chronic disease in the offspring. And this is actually the area where there's more emerging evidence. The Barker hypothesis is actually relatively old. It goes back to the 90s. And that's actually the hypothesis that the exposure to hazards during pregnancy can affect chronic diseases in the offspring when they grow up to be adults. And some of the original evidence comes from the studies where they showed that very poor nutrition during pregnancy can lead to low birth weights, and then later when the offspring grow up, they are more prone to cardiovascular disease, hypertension, and diabetes. So when we think about hazardous exposures, it's helpful to think about three different time frames or periods, I guess. So it's before pregnancy, during pregnancy, and after pregnancy. Before pregnancy is a very important period and often overlooked. So first of all, there could be effects on maternal hormones, and I will be mentioning endocrine disruptors later. Effects on oocytes. You know, we do not develop new oocytes after birth. It's, you know, if they are damaged, they are damaged. So there are no repair mechanisms. In some situations, there could be an increased body burden if there are persistent pollutants, such as, for example, PCB, could accumulate in the body and then later affect fetal development during pregnancy. The next time frame is the pregnancy itself. So the first two weeks is early division and implantation, followed by embryonic development, also referred to as primary morphogenesis, which occurs very early during pregnancy, starting week three, where people often don't even know that they're pregnant. And starting with week nine, this is fetal development. It continues to birth. It overlaps with organogenesis, which continues a little bit beyond birth. And then after pregnancy, there could be direct effects of hazards, and also importantly, indirect effects via lactation. So before pregnancy period, so the effects of environmental hazards on oocytes, so just to remind you that oogonia begin their first meiotic division in utero, and then the primary oocytes develop, and we are born with primary oocytes. They are arrested until follicular activation. So if we think about the acute toxicants that are more likely to affect dividing cells, so in comparison to, let's say, male germ cells, oocytes are somewhat less susceptible to those acute effects. Not to say that they're not susceptible at all, it's just, again, relatively speaking. However, at the same time, they're way more susceptible to cumulative effects over time of various occupational and environmental exposures, and together with the aging process and oocyte senescence, this contributes to DNA damage, mutagenesis, chromosomal abnormalities, importantly epigenetic alterations, and I'll be mentioning arsenic, how it does it, and destruction of the oocytes. And as a result, this could lead to decreased fertility, spontaneous abortions, abnormalities in the offspring, and I already mentioned chronic disease in the offspring. The April of this year was one of the very recent publications in environmental research where a Danish group looked at the cohort of females who were occupationally exposed to diesel exhaust, and they found that when mothers are exposed to diesel exhaust, their offspring has higher risk of developing breast cancers, and specifically is the breast cancer with the early onset at 51 years of age and earlier, and the type which is estrogen receptor negative. That's the one that's more likely to occur due to the environmental challenges as opposed to genetic predisposition. So this is a different way of looking at the various periods during pregnancy, and if you look at the green parts, so it's the first two weeks, that's where fertilization, cleavage, blastulation, implantation, and gastrulation happen. Gastrulation is an important period when we think about possible effects on epigenetics because epigenetics is something that controls gene expression, and that's where the cell differentiation happens, and there are a lot of epigenetic changes, so that's where major abnormalities can happen, and then starting at week three, that's primary morphogenesis or embryonic development, and if there are any disruptions here, they can lead to disastrous outcomes such as neural tube defects and others. Starting at week nine, it's organogenesis and fetal development, and any disruptions here can result in somewhat less pronounced morphogenic abnormalities, but pretty bad outcomes nevertheless, such as microcephaly, cognitive impairment, hearing loss, which I'll be mentioning later. And after birth, I just want to briefly mention breast milk. So xenobiotics that tend to get into the breast milk are the ones that have low molecular weight, they're lipophilic, and they're nonpolar, actually exactly the same characteristics that are needed to cross the placenta, and here just, you know, there are many xenobiotics that can enter the breast milk, but I'm mentioning two here, polychlorinated biphenyls, which are the persistent pollutants, and DDT, which is an organochlorine pesticide, still used extensively in many parts of the world to control malaria. So I've mentioned epigenetic changes a couple times already, and I want to spend a little bit of time explaining it, because I think it's a fun part, and I can talk a little bit about the molecular mechanisms underlying it. So epigenetic changes affect gene expression without changing changes, without actually causing any changes in coding of the DNA sequence. Very often when people say epigenetics, they really refer to the changes that are stable and heritable, and this could be a bit confusing, because epigenetic changes, some of them are stable and some of them are temporary, because, you know, when cells differentiate, when cells respond to various milieu and the changes in the environment, there is a constant change in the epigenome, which affects gene expression, but then at the same time, there is also a certain part which remains stable and importantly heritable. And it leads to inter- and transgenerational effects. So, and these are the three actually most important ways how epigenetics can change gene expression. DNA methylation, histone modification, and through non-coding RNA, specifically micro RNA. And I will mention all three of them later. So since I'm going to be talking about arsenic, just to briefly remind you about the sources of exposure. So when it comes to the occupational exposure, probably the most important area is construction workers and carpenters, and this is mainly because of the contact with chromated copper arsenate or CCA treated wood. Since 2014, the residential construction pretty much does not have CCA treated wood in both Canada and the U.S., but other construction may still use CCA treated wood and of course when there are any sort of renovation work or carpentry involving older structures or older wood, that's where the exposure may be important. Non-ferrous metal production and processing industry, for example, smelting where arsenic is a by-product of metal processing. And others, for example, gallium arsenide and semiconductor industry and some pesticides that have arsenic. There could be significant environmental exposures, again, related to CCA treated wood with old playgrounds, old decks. In some parts of the world, depending on the geography, there could be contaminated well water. And in fact, most of the studies that are done on the effects of arsenic in pregnancy and on children are actually in those areas where they look at the contamination of arsenic in drinking water. And sometimes it could be from food, for example, rice is grown in contaminated ground. Health effects of arsenic are multiple. Arsenic is an important carcinogen. It's IR group one. And this association is based on the evidence that it causes lung cancer, which is mainly due to inhalation. And also bladder cancer and skin cancer. And these two cancers are mainly due to ingestion. Ingestion can also lead to lung cancer, but just less often than inhalation. And there is also relatively strong association with kidney cancer and hepatic cancer, such as angiosarcoma of the liver and hepatocellular carcinoma. And there are various many other chronic health effects. These are just some of the examples. Dermatologic, such as hyperkeratosis, cardiovascular effects, vasospasm and gangrene with the well-known black food disease in occupational medicine, enhanced atherosclerosis, hypertension, and the classic symmetric painful peripheral neuropathy. So why am I emphasizing the sort of cancer? Because the molecular mechanisms that underlie carcinogenesis often are at play that affect the development of the fetus. So it's generally not a good idea to be exposed to carcinogens during fetal development. And there are some overlying molecular mechanisms that can cause both effects. And later I will be also mentioning about cancer in the offspring. So a long time ago, cancer was considered a product of genetic abnormalities or mutations. And it still holds true for some of the carcinogens. But there's an increasing understanding that many carcinogens are not genotoxic. They may trigger cancer through some other mechanisms and, importantly, actually epigenetic changes. Some carcinogens can also be called co-carcinogens when they require a second carcinogen to produce an effect. And, in fact, arsenic is a really poor mutagen. It's been shown in vitro that it doesn't really produce a whole lot of mutations. So it's actually thought that it is mainly a non-genotoxic carcinogen and it works through changes in the epigenome. And here are some of the reproductive and developmental effects. Now I already mentioned that most of the studies that lead to this confusion come actually from the environmental exposures to relatively low lead, sorry, arsenic, relatively low level arsenic in drinking water. So the odds ratios that I mentioned here for spontaneous abortion and stillbirth is really from studies of maternal exposures to drinking water that had at least 50 micrograms per liter of arsenic. Congenital malformations, it's still debated because the evidence from humans is really poor. There's a lot of evidence from animals that arsenic can cause congenital malformations. And interestingly, there are also latent health problems in the offspring, particularly cancer, and particularly it's lung and bladder cancer. So when mothers are exposed to contaminated well water, contaminated with arsenic, their offspring is more likely to develop lung cancer and bladder cancer later in life. So in 1950s, Conrad Waddington, who was a developmental biologist in the UK, came up with the definition of epigenetics. So according to his definition is the interaction of genes with their environment, which brings the phenotype into being. However, it was not clear at all how this interaction really happens. With our understanding of the molecular biology, evolved our understanding of the epigenome. So now we can sort of look at this paradigm more as really the interaction between genes and the epigenome. And the epigenome is really tells which genes should be expressed and which genes should be silenced, and this results in a phenotype. And the environment can have direct effects on the genome. It can possibly have direct effects on the epigenome, but it's probably relatively more rare, and more likely it works through some other levels. For example, hormonal alterations, and I'll be talking about endocrine disruptors later. And then it modifies those exogenous cues, and exogenous cues then signal epigenome to affect gene expression. So I mentioned three different ways how epigenome can affect gene expression. So DNA methylation is the most commonly understood, and if you remember DNA sequence, there are four nucleosides. There is adenine, cymidine, cytosine, and guanine. And methylation happens at cytosine, and it's specifically when cytosine is followed by guanine, so-called CG or CPG motifs. So at these CG motifs, cytosine gets methylated with an enzyme called DNA methyltransferase, and there are different types of DNA methyltransferase. Some of them are more important in actually that most stable expression, and some of them are more important in the temporary changes in the epigenome. And SAM, or S-adenosylmethionine, is a very important methyl donor in this process. It donates methyl group to methylate cytosine, and it becomes S-adenosylhomocysteine. And this mechanism is actually important to remember when you think about how arsenic affects this process, and I'll be mentioning it later on. So there are different areas in the genome where we have CG motifs. Importantly, promoter regions of our genes are enriched with CG motifs, and if those CG motifs in promoter regions are unmethylated, this results in gene expression. If they are methylated, this triggers gene silencing. This is a very important mechanism, if not the most important mechanism, how various genes are expressed or silenced. So it's been shown that arsenic has very significant effects on the epigenome. And arsenic, first of all, affects the availability of the methyl donor SAM, because if you remember arsenic metabolism, arsenic requires methylation to be metabolized into its more toxic metabolites, which is MMA and DMA, and during that process of metabolism, it consumes SAM. As a result, there is less enzyme activity, but there are also some other less known direct ways how arsenic actually suppresses activity of DNA methyltransferase, and there are some changes that have been observed in the epigenome upon arsenic exposure is decreased global methylation. Now, I mentioned CG motifs in the promoter regions, but they're also present in between genes, so when we talk about this global reduced methylation, it's more about those other regions that are not methylated, and this actually also often leads to genomic instability, actually also a hallmark of carcinogenesis, often present during aging process, and I'm probably digressing a little bit, but I think it's a fun fact that the methylation patterns change as we age, to the point that right now, like scientists talk about the epigenetic clock. If we take our peripheral blood cells, and if we look at the methylation pattern of our peripheral blood cells, we can actually estimate our chronological age within an era within four or five years, and some people who are sort of more prone to chronic disease and kind of faster sort of aging, they have the so-called epigenetic age acceleration, sort of more accelerated changes in the epigenome, so it's actually another fascinating area, but I'm somewhat digressing from the topic, but it's just to say that epigenome controls everything. It controls aging, it controls carcinogenesis, it controls our development, it controls development of many diseases. So in addition to global decrease in methylation, there has also been observed that upon when arsenic, with the exposure of arsenic, there is targeted hypermethylation of certain genes, and importantly, tumor suppressor genes, such as P16 and P53. So you remember hypermethylation means gene silencing, so if you silence a tumor suppressor gene, this promotes oncogenesis, and it can also affect the development. And I already mentioned that, maybe again going back, that when mothers are exposed to arsenic, the offspring is more likely to develop lung cancer and bladder cancer in the future, and this could be one of the possibly likely mechanisms behind it. So besides DNA methylation, which is a bit better understood, there is another level how epigenome affects gene expression, and this is through histone modification. So if you remember, DNA is wrapped around histones, proteins, and different modifications of histones make chromatin, which is basically DNA and histones, to be more compact, which is more sort of like heterochromatin, or more loosely packed as euchromatin. So when chromatin is more densely packed, gene expression is silenced, and when chromatin is more loosely packed, that's when gene expression happens. And one of the mechanisms to affect histones is through acetylation, and that happens at lysine. So acetylation of lysine results in loosening of the chromatin, and deacetylation results in more dense chromatin, and that's another way to affect gene expression. So besides acetylation, there are other processes. There is phosphorylation, ubiquination, somylation, et cetera, with sort of more complex effects on chromatin structure. And just to say that arsenic actually changes these patterns, it's a little bit less understood how it sort of affects disease, but it's been shown that the patterns are changed significantly. It can cause acetylation in some places and deacetylation in other places. And finally, the last way how epigenome can affect gene expression is through so-called non-coding RNA. And a bit of a fun fact, if you may or may not remember that only 1 percent of our genome actually codes for protein, which is quite remarkable. And many years ago, the rest of the genome was called so-called junk because people just didn't understand what it does. Again, with the development of molecular biology, it's now clear that these other regions are actually very important. They control gene expression. And close to probably 90 percent, or definitely more than 80 percent of that so-called non-coding DNA is actually transcribed into non-coding RNA. And why it's called non-coding RNA is because it's not translated into proteins. But it has an important function. It controls translation of other proteins. So an important example of non-coding RNA is microRNA. So microRNA just simply is because it's short, it's about 22 nucleosides length. It travels to ribosomes or travels to the sites where a protein is produced and looks for complementary messenger RNA. So when those little pieces of microRNA find complementary messenger RNA, they bind to them and then this leads to degradation of messenger RNA. And if this doesn't happen, then the messenger RNA is free to go and get translated into a protein. So it's a very important way of either silencing or maybe more importantly doing some kind of like dose response or affecting how much of a protein is really produced. Arsenic has also been shown to affect microRNA expression profile. But among all these three types of epigenetic modifications, this one is the least well studied simply because of the tools that are needed to study mRNA as opposed to DNA. So moving to endocrine disruptors. So endocrine disruptors are hormonally active agents. There are many, many of them and they have many various ways how they can affect our endocrine system. Some of them are xenoestrogens. So they act through our estrogen receptors. Others include DDT, other organochlorine pesticides, bisphenol A, which could be found, for example, in epoxy resin products and epoxy resin lining is used in various cans for our food and beverage. So there is a lot of environmental exposure in addition to occupational exposure. These affect ovulation and importantly, they are obesogenic. So also, you know, there's sort of hypothesis, you know, but that was sort of epidemic of obesity, how much of it actually comes from the endocrine disruptors in the environment. Some other agents are anti-antigens. These examples include PBDs or polybrominated diphenyl ethers. Important usage is in flame retardants, phthalates, which are in various plastics, some food packaging, even some cosmetics. And these have significant effects on male reproductive system, but also can lead to early pregnancy loss, increased weight gain during pregnancy. Aryl hydrocarbon receptor is a very important receptor in regulating reproductive system and endocrine system. It's also called dioxin receptor, named after dioxin because dioxin acts via this receptor. In addition to dioxin, which is a product of incomplete combustion, polyaromatic hydrocarbons and PCBs are also known to act via aryl hydrocarbon receptor and trigger very complex pathways because the downstream signaling from this receptor involves estrogen, androgen and progestin modulated pathways, so very complex signaling results. Some toxicants have direct toxicity to testes and ovaries. Examples include arsenic-led cadmium. Some have direct effects on thyroid function. So just one example is PBDs, and some affect glucocorticoid metabolism. And one example is, there are definitely many, but I just put one example there, which is DDT. So moving, shifting gears a little bit, so just now I just want to mention just some select hazards that seem to have more critical windows during the pregnancy. So some of the examples of biological hazards that I would like to mention are varicella and parvovirus B19, which are more important during the first 20 weeks of gestation. So varicella, so insusceptible mothers, if they're infected, it's estimated that two to three percent of fetuses develop congenital varicella syndrome, which includes various malformations of CNS, eye and limb. And we have a very good prevention, obviously we have vaccination that has to happen before pregnancy. It's a live vaccine, so it's contraindicated in pregnancy, but knowing the vaccination status prior to pregnancy is important, and that's the important prevention. Parvovirus B19 is where we do not have a vaccine, however, if females were exposed to parvovirus B19 in the past, they're deemed immune and not susceptible. A critical window is also considered first 20 weeks of gestation. It's not a 100 percent clear cut, sort of cut off, because sometimes exposures later can also lead to fetal high drops, but it's very rare. It's way more dangerous if the exposure happens during the first 20 weeks of gestation. So it results in nonimmune fetal high drops, and the mechanism for this, it's not actually a teratogen, but it affects progenitors of red blood cells. And it may result in severe anemia in the fetus, and the severe anemia can result to just edema of the fetus, and there are multiple mechanisms involved, including potentially high output heart failure, increased capillary leak, portal hypertension that can result from extramedullary hematopoiesis in the liver, and sometimes there could be direct effects on the myocardium because parvovirus B19 is known to cause myocarditis. So as a result, there could be fetal high drops and fetal death. However, removal from the workplace is not routinely recommended. Researchers attempted to estimate the risk, and in early 2000s, there was a publication that there was an estimate that about 50% of females of the reproductive age are susceptible to parvovirus B19, and among those who are susceptible, there is about 20% risk of acquiring the infection during pregnancy. And among those who acquired the infection during pregnancy, CDC says that it's a little bit under 5% chance that it might result in fetal death and fetal high drops and fetal death. So if you sort of, if you use these estimates, 50% chance of an infection, sorry, of susceptibility, 20% chance of infection, 5% chance of fetal death, you come up with 0.5% risk. So that's based on those older estimates, 0.5% risk of fetal death. Later studies showed that 50% is probably, it's an underestimate of susceptibility, sorry, not susceptibility, but the immune status, and it's more than 60% of females in North America have IgG to parvovirus B19. So that already means that it's less than 0.5%. And also during the pandemic, we learned that masks and N95s are very effective in reducing our chances of actually contracting infection. So I would say that, you know, it should be recommended if pregnant women work in schools and kindergartens, it makes sense to wear mask or N95, and that reduces significantly the risk of contracting the infection, therefore reducing that 20% chance significantly. And then depending again on the critical time period during the pregnancy, it could be, it's whether it's 5% in the first 20 weeks of gestation or significantly less in the later part of the pregnancy. So these are the numbers that could be used in sort of risk communication. Another important fact is that women who have children at home are way more likely to contract parvovirus B19 compared to any exposures outside of home, whether you work at school or you work in the kindergarten, which is another important fact if you sort of think about the risk communication with a pregnant woman. Heat exposures. So there is some evidence that first trimester maternal hyperthermia increases the risk of neural tube defects. This comes from studies that were done for non-occupational exposures. Moretti and colleagues in 2005 did a meta-analysis where they looked at fever due to infection, exposures to hot tubs, saunas, and electric blankets. And they found that all those exposures result in almost two odds ratio of neural tube defects. So there is not a lot of literature on occupational exposures, and if you came across any, please let me know. But I think it is reasonable to extrapolate and at least be concerned that if there is sort of heat stress to women in the occupational setting, which may result in maternal hyperthermia, you would expect similar results. So I would be concerned with any sort of exposures to extreme heat environments during the first trimester during pregnancy. So you probably know that ACOM produces LEO guidance documents, and one of the LEO guidance documents is on pregnancy. I believe it was produced in maybe 2011 or so. This guidance document refers to Sports Medicine Australia, which recommends avoiding exercise in hot conditions and also makes a statement that exercising in warm environments should be limited and adequate hydration should be maintained with physical activity. So besides the concerns with the first trimester and neural tube defects, there are also changes in physiology of pregnancy, which predispose pregnant subjects to be more susceptible to heat stress simply because there is a decreased ability to compensate and decreased ability to be able to have this homeostasis. So it's more likely that pregnant subjects would be more susceptible to various negative outcomes of heat stress, and there will be definitely less tolerance. Anesthetic gases, hazards in healthcare workers. So with anesthetic gases, the evidence suggests that there is an association with reduced fertility, spontaneous abortion, and even congenital malformations. There are a number of studies, but I'll just mention one, which was done in British Columbia, where the authors looked at the retrospective cohort of nurses, and they looked at those who were exposed to anesthetic gases compared to unexposed. And they looked at both halogenated gases exposure and nitrous oxide. And they found odds ratios of about two to three, suggesting an association with particularly cardiac and integumental malformations in this cohort. So I'm just, well, I'm from Canada. So I'm mentioning here Canadian legislation, which, you know, most of the workplaces in Canada are under the provincial legislation. So in Ontario, there's Occupational Health and Safety Act. And as a rule, it doesn't prescribe things about any particular hazards, but actually anesthetic gases are sort of more of an exception to the rule, where there is a regulation under the Act on health care and residential facilities, where this regulation actually prescribes what's needed to be in place to reduce the exposures, particularly the use of and maintenance of scavenging systems, and also maintenance of the ventilation system to reduce the exposures to waste anesthetic gases. So shift work has drawn a lot of attention in terms of how it affects or doesn't affect health and pregnancy. Royal College of Physicians of the UK, in 2013, came up with a concise guideline based on under a systematic review where they looked at different types of shift work and how the shift work affects miscarriage, preterm delivery, small fegestational age, low birth weight, preeclampsia, gestational hypertension. And they found that out of all these outcomes, it's the miscarriage that seemed to be the most obvious, and out of different types of shift work, it's particularly fixed night shift work that seems to increase the risk. So the general population of reproductive females has about 12 cases of miscarriage per 100 pregnancies. And the fixed night shift work seems to increase that risk with an extra 6.1 cases, meaning 50% increase, and the graphic on the right could be used as a good sort of risk communication tool when you talk to workers. The authors, however, noted that this is based on low-quality data. They said it is uncertain whether there is an increase, but if there is an increase, this is the best estimate. So since then, there was a systematic review done in 2019 by Kay and colleagues who found similar findings. The only thing that they found was a 23% increase as opposed to a 50% increase with fixed night shift work. In addition to miscarriages, they also found a slight increase in preterm deliveries, and the preterm deliveries, the estimate was a 21% increase with fixed night shift work. The same two groups also looked at long working hours, long working hours as defined by working more than 40 hours per week. So the Royal College of Physicians group estimated 1.2 extra cases of preterm delivery per 100 deliveries, which is 18% increase, and two extra cases of miscarriage per 100 pregnancies as a 16% increase. And the 2019 systematic review found similar results with increase in preterm delivery by 21% and increase in miscarriage by 38%. Exposure to noise. There is some evidence that late, meaning after 20th week of gestation exposure to noise could lead to pediatric sensorineural hearing loss. The evidence is not very strong, but it is there nevertheless, and there is a sort of biological plausibility there. It's been shown that the association is particularly important with lower frequency noise, as the abdominal soft tissue better attenuates higher frequency sounds, and lower frequency noise meaning less than 500 hertz. And with higher frequency sounds, there are even some studies that say that it could be, sorry, with lower frequency noise, it can even be amplified through the abdominal soft tissue. So after the 20th week of gestation, if one looks at the peripheral auditory system of the fetus, it already resembles the adult. And it can respond to auditory responses after the 20th week. That's where is the first demonstration of fetal cochlear auditory responses. So based on this, the U.S. Navy and Marine Corps have actually a technical manual on reproductive and developmental hazards, and according to that manual, they recommend exclusion of pregnant subjects after the 20th week of gestation from discharging firearms. ACGIH, or the American College of Governmental and Industrial Hygienists, states that noise in excess of 115 dBc TWA, or peak 155 dBc to the abdomen, may cause hearing loss in the fetus. So talking about the third trimester of pregnancy, that's where all these changes in biomechanics become particularly pronounced. There is an increased body mass, especially the upper body mass. The center of gravity, as a result, shifts upward and away from L5-S1 level. There is an increased spinal load, especially during forward flexion. There is an increased abdominal girth, which impedes the ergonomic lifting. There is an increased spinal instability with increased anteroposterior postural sway, increased joint laxity, which contributes to decreased load-bearing capacity, and there are some changes in balance control where pregnant subjects are more likely to fall. So based on the biomechanics of pregnancy, NIOSH has weight limits for lifting, and I'm sure that you're probably familiar with it, but just in case I'm mentioning, because it's a very useful tool to talk to pregnant women, even for non-occupational exposures, when you talk about lifting, when you talk about daily activities, or maybe even heavy exercise at the gym. So you can easily download it if you Google NIOSH and lifting and pregnancy. So it has three charts, and the three charts depend on the frequency of lifting. So the very left chart is for those who lift less than once every five minutes, and I'm just going to focus on this one. And every chart is divided into before 20 weeks of gestation on the left and after 20 weeks of gestation to the right. And you can follow the chart. It's really easy to interpret. It depends on the lifting zones, how much women can actually safely lift, and that's, of course, talking about uncomplicated pregnancies. So average uncomplicated pregnancy, safe weight limits. Some of the key things to remember, that women during pregnancy should avoid any lifting reaching overhead. It contributes to balance and stability. They should avoid any lifting from below mid-shin. So there should not be any lifting from the ground. And then in the sort of most of the ergonomic zone, then it depends where you operate, and you can see a different sort of weight limits there. So in addition to this, lifting involving bending and reaching should be either minimized or eliminated, and also frequent stooping, bending, and squatting. And this has two main, I guess, sort of outcomes in mind. One is, again, the effects on the mother. With all the changing biomechanics, there is just simply more predisposition to musculoskeletal injury or falls. Pregnant subjects are particularly prone to low back pain during the six and seven months of gestation. That's where the prevalence of low back pain is at its peak. But there also could be fetal outcomes. And that's particularly with that sort of forward bending, possibly compromising the circulation to the fetus. And there is some suggestion that excessive lifting could result in preterm birth, small for gestational age babies, and an early pregnancy could result in miscarriage. And finally, very briefly, I want to talk about the positive effects of exercise. So again, talking about uncomplicated monozygotic pregnancies. And here's a list of risks that are associated with not participating in exercise activities. There is loss of muscular and cardiovascular fitness. There is excessive maternal weight gain, increased risk of gestational diabetes or pregnancy-induced hypertension, development of varicose veins and DVT, increased risk of dyspnea and low back pain, poor psychological adjustment to physical changes of pregnancy, and increased risk of falls. Also, regular physical exercise improves sleep during pregnancy. The Royal College in the UK recommends 150 minutes per week of moderate intensity exercise for pregnant subjects. And generally, I guess, sort of, you know, the OBGYNs recommend that as long as you can talk during your physical exercise, you're sort of in the safe, you know, in the safe sort of region that's kind of, I guess, separating moderate from strenuous exercise. So just some of the key points. So I just want, again, to emphasize that the period before pregnancy is very important because that's where, you know, the oocytes are there exposed to various occupational and environmental hazards. You cannot replace them. So all the safety controls at work, all the sort of our hierarchy of, you know, controls should be there to minimize the exposures, regardless, actually, of the pregnancy status for any reproductive age, female, or, you know, for any worker, for that matter. So it's not just pregnancy. And very early pregnancy can result in disastrous outcomes. Think about the third week of gestation where morphogenesis already starts. So I'll, so before I stop, so I have some of the references here, and they're available in the handout. My email is there. So I really encourage you, you know, reach out with your questions, comments, maybe additional resources to discuss anything related to pregnancy. I'm very interested in this topic. And I have to say, because I hurried to submit the handout before the deadline, so I have one significant omission there. And there is actually an ACOM guidance document published in 2016, which is a guidance statement on reproductive and developmental hazards and hazard management by John Mayer and colleagues. And if you have any sort of questions, if you want to look up the legislative landscape in the U.S. around pregnancy, that's a good document. Or any questions about the global risk management framework in pregnancy, that's the document to go to. And for some additional references. So I'm going to stop here. And I'll take any questions. We have a question from a virtual attendee that, in your talk, you had discussed. Sorry, could you just speak up a little bit? We have a question from a virtual attendee. In your talk, you had discussed the effects of arsenic as arsenate, and also the smelter oxide form. The question is, is it clear as to what form is more of the concern? Yeah, thank you for the question. So I tried to mention that I'm talking about inorganic arsenic. So I was not talking about organic arsenic at all. So it's inorganic arsenic. And there is not that much sort of literature on various sort of productions and how they affect the toxicity. Really most of the results that I showed were really the inorganic arsenic in drinking water. And that's the one that sort of metabolized into MMA and GMA. And there are more toxic metabolites that are produced that way. So hopefully that sort of answers the question. Thank you very much for that excellent review of pregnancy in the workplace, Dr. Afana Sayeva. I have to applaud you here, because no one can pronounce that. I usually go by Marina. All right, Marina. You asked if there were any additional information about heat stress in pregnancy. And I know for a fact that in the mid-1970s, the US Air Force changed their protocol for taxing fighter aircraft into the airports because of the complaint by the marshallers that they were being overheated by the targeting radar and microwave systems that they had up front. And since 10% of the female Air Force enlisted were pregnant at any one time, their concern was for that first trimester. So they actually had a procedure where they turned off those units on landing before they taxied in. So just to give you that information on that, that was a concern even back in the 70s. Thank you very much for that additional information. That's very interesting. Quick question. You said exposure to night shifts increases risk for preterm delivery and miscarriages, correct? And one of the populations you mentioned was fixed night shifts or fixed shifts. What is that? Is that someone who only works night shifts? Yes, exactly. So it's not a rotating shift. It's really when people work night shifts only. And the author specifically looked at different sort of types, like changing shifts and rotating shifts and working in the evenings. So it's specifically fixed night shift. There are maybe some increase with others, but the change is so small that it's hard to say whether it's significant and has any sort of biological, at least they couldn't detect any significant effects. I ask because I'm seeing more work restrictions that say no night shifts, and it's impacting the mission at my place at work. And so when I talk to the women's health consultant for the Air Force, she does not recommend restricting night shifts for pregnant women. But I don't know if there's a way for mitigating the risk, maybe alternating shifts. Do we know if that will reduce the risk? Well, that's, again, going back to that study, they found that other types of shift work have less of an increase. A lower risk. Yeah. But then again, even with that, the first group found 50% increase. The other group found 23% increase. They both say that the quality of data is poor. So again, it's hard to translate small increases based on poor quality data into sort of policy changes. And that's, it's a difficult area because, you know, you can debate is that significant enough or big enough to worry, or it's not big enough and, you know, all pregnant women should just continue fixed night shift. It's a hard question. I think in reality, it all comes down to can you accommodate? If there are ways to accommodate without, you know, undue hardship, it might be sort of, it might be reasonable to pursue that because there seems to be a little bit of an increased risk. However, this is miscarriage. So we're just talking about early pregnancy. And that's where it becomes sort of more significant. So you actually need to know that you're pregnant. It's about early, early periods of pregnancy. It's not about late term. Thank you. You're welcome. Good morning. Jan Mabee, U.S. Army. Morning. Do you have any information about vibration with wind turbines, as an example, and any stage of pregnancy and any effects? Yeah, you know, the only thing that I came across in the literature regarding vibration is direct vibration to the abdomen. That seems to be the one, because that sort of can be transmitted to the fetus, and it should be avoided. Do you believe that the vibration from wind turbine potentially might? I haven't seen anything about that. So it's... Okay. And actually, you're not the first... Keep our eyes open. Yeah. I haven't seen any of that. But it's actually a frequent question. Thank you for a very interesting presentation. Thank you. And very detailed. My question is on vaccines and the benefits of preventing these vaccine-preventable diseases before a woman gets pregnant. Oh, sorry. Could you just speak up a little bit? Yeah. I'm talking about vaccines and their benefits in preventing diseases in women that are likely to become pregnant. So with respect to COVID-19, seeing that pregnant women, especially during the peak of the pandemic, they were pregnant when they got infected, got very sick, and were more likely to need ICU care. Is there any recommendation for COVID-19 in pregnant women, or any plans for that, since COVID-19 seems to be trending towards becoming an endemic illness or disease that we're going to be living with for a while? And also, I don't know if you have any data from the COVID-19 vaccine registry, if there's any data that has been updated in terms of it having a clear-cut benefit-to-risk analysis from the data they're collecting. Thank you. Thank you. Well, that's a huge question, and I almost on purpose avoided talking about COVID-19. So I think what we've learned throughout the pandemic is that pregnant women should get vaccinated. Of course, there was a lot of fear during the pandemic, and many pregnant women avoided vaccination, and that was actually not a good decision, because pregnant women are at an increased risk for complications, and they should be considered the higher risk group. So they should definitely be encouraged to be vaccinated, regardless of the time in pregnancy, whether it's before pregnancy, early, late. So vaccine does not increase the risk to pregnancy. If anything, it reduces the risk of complications due to COVID-19. And in fact, there is also some evidence now that, especially if you get vaccination in the second half of the pregnancy, the antibodies are transmitted to the baby. So the baby is more protected during the first six months of their life, and they're less likely to also have bad effects from COVID-19. So it's all sort of positive effects, and the policies depend on the region, on the country, but generally, whenever boosters are recommended, pregnant females should be considered as a higher risk group, and they should get the boosters, and not fear the complications, because it's good for the mother, and it's also good for the baby during the first six months of life. Okay, and I think we, well, it's two minutes into the break, so I think break time. Thank you so much for attending. Thank you.

occupational hazards

pregnancy

academic curriculum

epigenome

reproductive toxicant

endocrine disruptors

varicella

parvovirus B19

exercise during pregnancy

Barker hypothesis