St. Louis Baby Tooth Study – Phase II: Frequently Asked Questions

Please keep all of your kit materials out of reach of children and animals at all times! Carefully open the outermost packaging, making sure not to lose or discard any materials inside the shipping box. Your package will include two separate kits, one marked “Blood Collection Kit” and one marked “Water & Toenail Collection Kit”, along with two ice packs and three sheets of paper.

Please take the two ice packs and place them in a safe place in your freezer, ensuring they are laid flat. This is important as they need to be flat in order to fit back into the “Blood Collection Kit”. You MUST have two frozen ice packs at the time of your blood draw.

BSI will contact you at your preferred email or phone number within a week of you receiving your kit to schedule your at-home phlebotomy (blood draw) appointment. Before you begin collecting any of your samples, please review the online instructions for blood, water, and toenail collection. To view these instructions please click here or go back to our main study page and then click “Sample Collection Instructions.”

In Phase I, we invited participants of the original Baby Tooth Survey who donated their baby teeth as children in the 1950s and 60s to join the St. Louis Baby Teeth – Later Life Health Study by completing a questionnaire on their personal history and an online cognitive test.

In Phase II, we will randomly invite about 1000 of the participants who have completed both the survey and cognitive test to donate blood, toenails (yes, toenails!) and tap water to our study.

Blood donation will be conducted through BSI, a professional laboratory service with licensed phlebotomists, while you will collect your own toenail and tap water samples. To view these detailed instructions including demonstrational videos please click here or go back to our main study page and then click “Sample Collection Instructions”.

The  goal of the St. Louis Baby Tooth Study – Later Life Health Study is to explore how early-life exposures relate to later-life health. Your previously donated baby teeth provide data about your early-life exposures. Deciduous teeth, also known as baby teeth, grow like trees, with the earliest-forming layers closest to the center, and the outer layers forming last. We can use your previously donated baby tooth to look at what you may have been exposed to while your tooth was forming, much like rings in a tree!

We can use the survey and cognitive test from Phase I of this study to explore links between your early-life exposures and later-life health. By participating in Phase I, we are able to use statistical methods to explore how your early-life exposures relate to your cognitive scores and self-reported health outcomes.

The blood, toenail, and tap water samples give us additional information on current exposures that we can add to the data from the teeth. That combined information allows us to use statistics to explore questions about the role of early-life versus current exposures and how they relate to your health now. 

The blood samples, in part, are contributing to ground-breaking research that explores how early life exposures impact extracellular vesicles and their contents. This is an important way that cells communicate.

By donating these samples, you are playing a vital role in helping advance the research on interactions between early-life exposures, current-life environment, self-reported health, and present-day measures of health. We are thankful for your interest in supporting us as we continue to explore and investigate health across the lifespan!

It is our goal to provide you with any relevant results of your teeth, blood, toenail, and water samples, but getting these results will take us some time and will require approval from our Institutional Review Board.

All of the samples we receive will be frozen and placed in carefully managed storage. Any and all access to these samples will be monitored by Harvard, our Institutional Review Board, and the study team. This allows us to continue our groundbreaking research as new analytical techniques are developed and more funding is secured. 

Some of the samples will be processed right away, like some of your donated blood. However, the analytical methods used are very new, and do not yet have any health implications. These methods will be looking at extracellular vesicles in your blood. You can read more about this in the FAQ below.

While we are exploring the best way to provide you with meaningful results, we have started a semi-annual digital newsletter for our participants. The first letter went out in February of 2024 and provided updates on what we are doing and information about the study! We are working on a second newsletter and we will send the newsletter to your preferred email, so please make sure we have your preferred contact information by clicking here to access our Phase II Update Information Survey.

Extracellular vesicles (EV’s) are tiny little pods that come from all the different cell types of your body. When they leave a cell, they wind up carrying parts of that cell inside them. It is thought that at least sometimes, these little packages are used to communicate and send information to other nearby cells. The things inside the EVs can be proteins, nucleic acids, or other molecules. The type of information within an EV, as well as the number of EV’s sent by one cell to another, can relay the presence of danger in the environment. Think of an EV as a letter from one cell to another letting them know whether or not they’re ok. If the contents of that letter simply says “HELP!” or if there are dozens of letters arriving every second, this would alert the cell receiving this communication that something is wrong. This is an important way that cells can communicate to one another when the body experiences a disease or is exposed to certain dangers in their environment. If this messaging system is dysregulated, it may cause a decrease or increase in messaging between cells. We are trying to see if we can identify different signals being carried by these EVs

EV’s are a relatively new field of research and have not been well studied in adults who may have had early life exposure to heavy metals. By examining EV’s and the things they carry in donated blood, we hope to gain more insight about how metal exposures can alter the structure and contents of EV’sin adulthood. This is preliminary research, and we cannot say for certain whether any results we find will directly impact an individual’s health.

However, we hope that by beginning to unravel these complex relationships, we will be able to see whether EV’s are impacted by heavy metal exposure, so that future research may expand on our work and potentially generate insights on any clinical implications for health.

We are randomly inviting about 1000 participants who have completed both the survey and cognitive test to join Phase II of the study. Unfortunately, this must be done through random selection, so we are unable to take volunteers unless they have already been selected.

If you have been chosen for Phase II, you will receive an invitation letter and further detailed instructions via email or physical mail.

To make sure that you receive your letter, please make sure we have your preferred contact information by clicking here to access our update information form.

If you completed both the survey and cognitive test portion of our study, and received an invitation to Phase II, you were one of the 1000 participants randomly selected to be invited to participate in Phase II of our study.

Phase II is expected to begin in the spring of 2023 and will run for about one year.

Nope! We will be continuing to run Phase I in parallel with Phase II. If you have received an invitation for Phase I, please continue to send in responses to both the survey and
cognitive test if you have not done so already.

Additionally, we are inviting all our Phase I participants to take another questionnaire expanding on the questions we’ve asked in the first survey, which began in September of 2024. Please look out for emails and letters from us about it!

We will send you all necessary materials for collecting blood, toenail, and water samples. All materials have been sterilized and approved by Harvard’s Institutional Review Board (IRB) and Harvard’s Office of the Vice Provost for Research (which oversees data safety and research compliance), as well as the National Institutes of Health (NIH), which is the sponsor of this work, to make sure we are up to every standard for human subjects research and data safety.

You will only be collecting toenail and water samples yourself. Blood samples will be drawn by a licensed phlebotomist that we will send (at no cost to you) to your home through our partnership with BSI laboratories (learn more here: https://biospecimensolutions.com/). We will send blood collection materials directly to you in the event that you agree to have your blood drawn at home. Please do not open or touch any blood collection materials yourself!

We will do everything in our power to make the donation process as clear and stress-free as possible, including sending a certified phlebotomist to your home and providing detailed instructions with demonstrational videos. If you face any limitations with a licensed BSI phlebotomist coming to your home, please let us know at slbt@hsph.harvard.edu as we may be able to find an alternate phlebotomy service!

If you would like to donate blood samples without the water and/or toenail samples, please still complete the invitation survey by clicking here. Please email us at slbt@hsph.harvard.edu to let us know that you will not be completing the water and or toenail sample collection.

If you do not want to donate blood samples, but would still donate toenail samples, please email us at slbt@hsph.harvard.edu, we may be able to work out a different way for you to return toenail clippings. At the moment, we are not taking water samples if you are not donating a blood sample.

Genes are very small units that carry information (DNA) about traits, functions, and even diseases. Scientists can learn about genes by taking the DNA out of a blood sample and doing a test called genotyping on this DNA. This test shows what information a person has inherited.

If you opt in to this optional portion of Phase II, we may genotype your blood for genes that might be related to environmental exposures like metals and later life health outcomes. For example, a gene called ApoE is known to be a predictor of dementia, and how metals affect cognitive function could be different depending on the ApoE genotype a person has.

We will not be genotyping your blood samples immediately so we will not have any results to share with you. When we do begin this process, we will discuss further with IRB to find appropriate ways to return any meaningful results to you. In the meantime, we have started a semi-annual digital newsletter for Phase II participants. The first letter was published in February of 2024 and provided you with updates on what we are doing and information about the study! We are working on a second newsletter, and will send it to your preferred email, so please make sure we have your preferred contact information by clicking here to access our Phase II Update Information Survey.

Yes! In the invitation survey for Phase II (found on our main study web page by clicking “Start Phase II!”) you will be able to opt out of genotyping. Scroll to the section titled “What will I be asked to do?” and click the box “No, you may not genotype my blood sample” at the bottom of the section. You will still be able to participate in the rest of Phase II.

For any questions on this process, please email us at slbt@hsph.harvard.edu for the fastest response, or 617-432-0041.

Yes – if we are made aware of potentially concerning health problems related to the samples we collect, we will contact you directly at the preferred email or address you have provided us. We will follow pre-established Environmental Protection Agency (EPA)/Centers for Disease Control (CDC) guidelines for determining this. For example, if your tap water contains higher levels of lead than recommended by EPA guidelines, we will reach out to you.

However, much of the work we are conducting is exploratory and has no pre-established links to health. For example, there are no current standards for “normal” vs. “concerning” levels of lead in baby teeth. We are presently trying to understand how such exposures may affect later-life health, but because of the inherently novel nature of our research, there are no guidelines about what may be too much! Your participation in this study, along with the information we gather from your baby teeth, personal survey, cognitive test, and biosamples will help towards the potential creation of such standards for future generations.

Due to a large volume of participants and samples, we will not be able to test all samples immediately upon receiving them. It will take some time for your samples to be tested. Please contact your trusted local health providers with any questions regarding urgent medical issues.

Our entire study, including any method of using or accessing your biosamples or data, is monitored by Harvard’s Institutional Review Board (IRB) and Harvard’s Office of the Vice Provost for Research (which oversees data safety and research compliance), as well as the National Institutes of Health (NIH), which is the sponsor of this work, to make sure we abide by every standard for human subjects research protection and data safety.

Additionally, all personnel on the study are required to be certified in human subjects protection training. We take every precaution to make sure all biosamples and data stay private.

After the study is completed, your data would only be made public if it was completely anonymized—meaning any and all personally identifiable information was removed—so no information could be traced back to you. As underlined in the Phase II consent form (if you would like to access a PDF copy of the Phase II consent form please click here), we will never use your biosamples in the creation of immortalized cell lines. In short, this ensures your samples will undergo the least possible handling and cannot be mass-replicated for use in any biological experimentation.

To ensure your confidentiality during the collection process, we have assigned you a lab ID that is different from your study ID number. This ID will be visible on the collection materials. You do not need to remember this number; we will only ever ask for your 6-digit study ID found on your invitation letter.

You can reach us at slbt@hsph.harvard.edu or 617-432-0041 with any questions. We will do our best to get back to you as soon as possible! Please note that it is easier for us to respond to emails than phone calls, so please try to email us first.

Yes! If you have requested to be notified about published papers in Phase I either by email or through our update information form and we have your preferred contact information, we will make sure to let you know when we begin publishing papers about Phase II as well. If not, please opt into being notified when we publish papers and make sure we have your preferred contact information by clicking here to access our Phase II Update Information Survey.

No, you can complete the 3 sections (blood, water, and toenails) in any order that you like (but see below about water collection). We understand that getting your blood drawn by mid-afternoon on a Monday is a tall order, so it may be easier for you to complete the water and toenail collection first.

We do ask that you hold off on collecting your tap water samples until after your toenails are clipped, so there is less time for the water to become contaminated. If you need to collect your water samples more than a few days before you can clip your toenails, then please keep your collected water samples in a cool dark place, such as your refrigerator or a cabinet, away from your stove.

After you agree to participate in Phase II by answering and submitting our invitation survey, we will ask our kit manufacturer to send you a kit to the address you have provided. The kits are shipped from Midlands GA, and should take less than 2 weeks to arrive, but please allow at least 4 weeks from when you submit your survey for the kit to be packaged and delivered to you. If you have not received your kit in 4 weeks, please let us know at slbt@hsph.harvard.edu or 617-432-0041.

If you lose your ice pack or any other blood kit materials, please let your BSI contact know as soon as possible. They will work with us and our kit distributor to get you the supplies that you need.

If you lose supplies from your water & toenail kit, please let us know as soon as possible at slbt@hsph.harvard.edu for the fastest response, or 617-432-0041.

After you agree to participate in our study by answering and submitting our invitation survey (found on our main study web page by clicking “Start Phase II!”), please view our online sample collection instructions by clicking here or by going back to our main
study page and then click “Sample Collection Instructions” and then “Blood Collection Instructions”. These instructions will provide more information on blood sample collection, as well as on our partnership with BSI laboratories, who will be sending a licensed phlebotomist to your home at no cost to you.

We will send blood collection materials directly to you in the event that you agree to have your blood drawn at home. Please do not open or touch any blood collecting materials yourself!

BSI laboratories will contact you directly to schedule your at-home blood draw, which will take place Monday-Thursday at your convenience, though we strongly encourage participants to have their blood drawn earlier in the week to allow ample time for our lab to process your samples. Please let us know if BSI has not contacted you within two weeks of receiving your kit. For any other scheduling concerns or difficulties, please contact BSI directly at the number they text or call you from.

Please also make sure to put your provided gel packs into the freezer at least 2 days before your scheduled appointment.

Immediately after your blood draw, complete the online Blood Collection Questionnaire by clicking here or go back to our main study page and then click “Sample Collection Instructions” and then “Blood Collection Instructions” and scroll down to “STEP 5: After your blood draw”.

We need your donated blood samples returned to our lab as soon as possible to minimize sample degradation. Your samples will be shipped with the ice packs that you will freeze before your appointment, but to make sure they stay cold the entire time, we are shipping them FedEx priority overnight. Your BSI phlebotomist will make sure they have enough time to draw your blood and make it to your local FedEx’s last pickup time so it arrives at Harvard by the next morning.

We strongly encourage all our participants to have their blood drawn on a Monday so that our lab staff can have extra hands ready to prepare your samples for our specialized deep freezers. If it is not possible to have your blood drawn on Monday, we would still encourage you to have your blood drawn earlier in the week to give our lab ample time to prepare and freeze your samples once they arrive!

BSI will contact you at the number or email you provided to us in your invitation survey. Please check your spam folder or spam settings if you have not been contacted within 1 week of receiving your collection kit. If you believe you have not been contacted or your contact information has changed from what you provided us in the invitation survey, please email us at slbt@hsph.harvard.edu for the fastest response, or 617-432-0041.

Please try to stay properly hydrated by drinking plenty of water before your blood draw! Blood is more than half water, so staying properly hydrated will make your blood draw quicker and easier.

For water collection questions you can contact:

• Elsie Sunderland, ems@seas.harvard.edu, 617-496-0858
• Mona Dai, monadai@g.harvard.edu

All other questions should be directed to the main study helpline at slbt@hsph.harvard.edu for the fastest response, or 617-432-0041.

You may or may not have at-home water treatment. The two most common are whole home systems and point of use systems. Here are some examples of both:

• Water softening units, activated carbon filters, or reverse osmosis systems that are typically installed near the water meter, in the basement, or in a utility room
• Neutralizing filters that are usually installed after the pressure tank and before any other treatment systems.
• Point-of-use filters, such as Brita faucet filters, that are often found under your sink or on your faucet.

Please note that you do not need to bypass the sediment cartridge filter typically located in the basement and plumbed just after the water pressure tank.

If you don’t know what type of water treatment systems your home has or can’t bypass those systems, please do your best to avoid the ones that you can. We understand that bypassing water treatment systems may be especially difficult if you live in an apartment or condo! You will be able to provide more information about your sampling location in our brief survey after you collect your samples (in Step 5 of the water collection instructions).

If you don’t know what type of water treatment systems your home has, please do your best to avoid the ones that you do know about, for example, a point of use filter on the faucet of your kitchen sink. We understand that bypassing water treatment systems may be especially difficult if you live in an apartment or condo! You will be able to provide more information about your sampling location in our brief survey after you collect your samples (in Step 5 of the water collection instructions).

If you can’t bypass some or all of your home water treatment systems, please do your best to avoid the ones that you can. For example, if you can’t bypass your water softening system, but you can temporarily remove a point of use filter on the faucet of your kitchen sink. We understand that bypassing water treatment systems may be especially difficult if you live in an apartment or condo! Please don’t worry if you are unable to bypass some or all of your water treatment systems. You will be able to provide more information about your sampling location in our brief survey after you collect your samples (in Step 5 of the water collection instructions).

We ask you to wear gloves to collect your water samples so that any trace materials on your hands do not get into your collected water samples. We are not asking you to wear gloves to protect you from your water (though they will keep your hands dry)! If you are concerned about your tap water quality, your local municipality may offer free water testing through their website or other online services.

While stainless steel nail clippers are ideal, whatever you use to regularly clip your nails will work! Please make sure they are clean before you use them.

We ask that you wait at least 3 weeks since the last time you’ve trimmed your toenails to collect your toenail samples. If you don’t remember when you last trimmed your toenails please wait 3 weeks to make sure we have enough material.

We don’t have a specific length your toenails need to be, because everyone’s nails grow at different rates, but 3 weeks should give us plenty of material to analyze.

Toenail clippings can allow us to examine your current exposure (if any!) to heavy metals. This is still a relatively new technique that will give us data to improve our study, but may not have any clinical health implications. We also won’t be testing your toenails immediately upon receiving them, so we will not have any results to share with you.

When we do begin this process, we will discuss further with IRB to find appropriate ways to return any meaningful results to you. In the meantime, we have started a semi-annual digital newsletter for Phase II participants. The first letter went out in February of 2024 and provided you with updates on what we are doing and information about the study! We are working on a second newsletter and we will send it to your preferred email, so please make sure we have your preferred contact information by clicking here to access our Phase II Update Information Survey.