After years of treating pregnancy loss and following long term patients with known thrombophila, a secondary benefit of improved cardiovascular health is emerging. This talk seeks to underscore the importance of treating the whole patient and prevent not only pregnancy loss but maternal cardiovascular disease. We all know the statistics on pregnancy loss, we see the grief it causes, and we know about many predisposing factors. But we still don’t have a way of pulling it all together. My talk will review thrombophilias as a cause of pregnancy loss (both stillbirth and miscarriage) and present newer tests. I will focus on why these tests become essential in the third decade of and life. I will show through case histories the implications of failed pregnancies for future maternal cardiovascular health. I will present a more holistic and multidisciplinary approach to prevention.
Dr. Barbara C. Toppin is a board-certified and beloved OB/GYN award winning physician, surgeon, and a founding partner of Adefris & Toppin Women’s Specialists, M.D.P.C. in Woodbury, Minnesota, also serving the Twin Cities Metro Area. She is an integral part of the team, bringing extensive expertise on a range of women’s health care topics. She has held numerous roles throughout her career before coming to Woodbury, including clinical instructor at Columbia University College of Medicine in New York and medical director at the Ossining Open Door Clinic in New York, and private practitioner in White Plains, New York. In support of her passion for preventing pregnancy loss, Dr. Toppin has accepted a board
of directors position with the Star Legacy Foundation. During her 24 years in Minnesota, she has been called on to provide medical commentaries for many local and national news outlets. Dr. Toppin has also been a featured guest on local talk shows, where she has discussed various medical topics related to her expertise in women’s health and wellness.
For her hard work and dedication, Dr. Toppin has been recognized with numerous awards and distinctions, including Super Doc and Top Doctors in Minneapolis St. Paul Magazine. She was also honored as a Top Obstetrician/Gynecologist in Woodbury, Minnesota, by The International Association of Obstetrics & Gynecologists. She is the author of the book “One in Four: Shifting the Balance on Pregnancy Loss.” She is currently in the process of authoring a second book on the topic of recurrent pregnancy loss.
Dr. Toppin has disclosed that she does not have any real or perceived conflicts of interest in making this presentation.
Jill Mason: Dr. Barbara Toppin is a board-certified OB/GYN and award-winning physician, surgeon, and a founding partner of Adefris & Toppin Women’s Specialists in Woodbury, Minnesota. Her previous roles include clinical instructor at Columbia University College of Medicine in New York and medical director at the Ossining Open Door Clinic in New York. In support of her passion for preventing pregnancy loss, Dr. Toppin serves the Star Legacy Foundation Board of Directors. She is the author of the book, One in Four: Shifting the Balance on Pregnancy Loss, and is currently in the process of authoring a second book on the topic of recurrent pregnancy loss. Please welcome Dr. Toppin whose presentation is titled, Even More Reasons to Prevent Pregnancy Loss.
Dr. Barbara Toppin: Good day. My name is Dr. Barbara Toppin, and I am an obstetrician gynecologist practicing in Woodbury, Minnesota. I’m here to speak to you about even more reasons to care about stillbirth and miscarriage, as if we needed other reasons. But believe me, there are a multitude of other reasons. My question to the medical population at large is, why aren’t we already doing this?
My first slide is about prevention, and I chose prevention because it’s near and dear to my heart. It’s something that I spend most of my time trying to do. I’m trying to prevent pregnancy loss, stillbirth, miscarriage, complications of pregnancy, preterm labor, and problems that may occur after patients are no longer child bearing.
As I said, it’s near to me. However, medicine at large has a difficult time with the word prevention because you can’t prove something was going to happen had you done this or that? There’s no way to prove prevention. If an obstetrical patient has a full-term baby vaginal birth, no complications, the baby’s well, mom’s well, no one’s going to pat the doctor on the back and say, “Congratulations, you prevented a stillbirth.” “Congratulations, you prevented an abruption or a miscarriage.” They’ll always say, “Well, that wasn’t going to happen in the first place.”
When we look at prevention, we have to start changing our mindset. It requires a change of mindset, in fact. We have to admit that there’s a potential problem that’s lurking out there for an individual. We have to say, “We’ve examined this patient. We found these problems. She’s not pregnant, but these problems may cause a problem in the pregnancy or during pregnancy.”
We want to change that mindset, and then we want to promote awareness. That promotion of awareness is not just internal. You’re going to spread the word to everyone. You want to promote awareness to your patients. You want to promote awareness to your colleague just as the stillbirth summit is doing here. We’re spreading the word to as many people as we can to help prevent problems for patients during pregnancy.
Finally, prevention is collaborative. Which means that we have to speak to our colleagues. We have to reach out to them and find out what’s new on their horizon. We want to speak to our hematologists, our cardiologists, our perinatologists, our rheumatologists, whatever specialty we need to speak with, we need to reach out to them because often they have knowledge of certain new trends or treatments that we may be completely unaware of.
Unfortunately, like most specialties, we all in OB suffer a bit from tunnel vision. We’re staying in our lane, looking at the baby. We want to get the baby out. We want to deliver the mom, and of course, we want good outcomes, but we’re farming problems out to different people. She’s diabetic and we’re not really thinking about the impact of the placenta. Or she has thyroid disease, and we’re not really thinking about the possibility of miscarriage. We want a pulling together of all of these things, again, communicating with our providers.
Unfortunately, we don’t see that. With as many methods as we have of communicating nowadays, we are communicating less. It’s really easy to send a referral letter out, but it’s a little bit more difficult, but more rewarding when you actually pick up the phone and speak to your specialists. If I have a medical concern about one of my problem patients, or one of my pet patients, I will call the specialist involved.
If the patient has had a clotting problem, I’ll call the hematologist and get them on the phone and say, “What do you think? This is what’s going on? Can you help me? Can you help her? What should I do?” Why? Because that makes the individual provider stand up and say, “Wow, this woman’s really concerned about this patient. I’m going to give her all I can.” It’s much better than a letter, which takes time. Pick up the phone, it doesn’t take too much time. Communication is going to trump tunnel vision every time. We don’t want to stay in our lane, we want to learn as much as we can from new trends and new medications and new treatments from our fellow providers.
With that, I’m going to present a case history. This is the only case history I will be presenting today. This case history is a patient of mine. She’s been my patient for 17 years. She is a local doctor. At the time she was 32 years old and she had never had a baby.
This is a case history on a 32-year-old physician patient of mine who presented with no history of illnesses or surgeries, no allergies, no drugs, alcohol, no GYN pathology whatsoever, and no toxicities. However, she did present with a very strong family history of unexplained recurrent pregnancy loss. With that, came an equally strong fear that she too would succumb to recurrent pregnancy loss, or worse never be able to have children as she was starting a family at a later age than her relatives had.
She was extremely worried by this and tried to do research and looked things up to find out if it was related to genetics or if it was simply just bad luck as had been suggested to her, but she couldn’t find much. And so, when she presented, she was quite worried. We asked her for an in-depth family history and were able to find out from the detailed history that there was a strong history of hyperlipidemia and heart disease. We did a physical examination, which was normal. She was active, had a perfect BMI, and really could find no reason for any medical concern. In fact, she had been to another physician that said she was fine, to take prenatal vitamins, and no workup was needed.
I ask you at this point, what you would do as providers, or as a patient? You can write your answers in the chat window. There’s nothing right or wrong. What we’re doing is simply having a discussion here. Do we refer out? Do we do a workup? Do we not?
Being who I am, however, I decided to treat her as if she had already had miscarriages. With that, we did a series of tests and the series revealed that she had a thrombophilia called Factor V Leiden. We were able to successfully treat her with Lovenox or heparin. She never miscarried. She had two babies without any complications. That really should be the end of the story, and for most physicians it is. Healthy baby, healthy mom, we’re happy, everybody’s happy.
But at her postpartum visit, I gave her some advice on not taking oral contraceptives or hormonal replacement due to the cardiovascular risk associated with that and the Factor V. To continue to take aspirin, have a stress echocardiogram at age 50, and we placed an IUD.
I’m sure you’re asking at this point, what’s the big deal? What does this have to do with stillbirth and miscarriage? I want to note here that this patient had the most up to date treatments at the time, and she had the most up to date testing, which involved a lot of thrombophilia testing and a regular lipid profile which was normal. Completely normal.
Again, what does this have to do with stillbirth? Well, let’s look a little bit beyond stillbirth. I pose a question. Did you know that according to Brown et al, pregnancy is essentially a stress test for women and these adverse pregnancy outcomes can be used to identify women who are at an increased risk for heart disease, even in those whom the condition have resolved after delivery? We’re talking about preterm labor, diabetes, gestational hypertension, preeclampsia. They all go away after the patient delivers. However, they are indicators of future problems. Just in the way a patient’s thrombophilia may be an indication of a problem during pregnancy.
My observations are that the care of women is on a continuum. A continuum according to Webster is a collection, sequence, or progression of values or elements varying by minute degrees. We need to consider patients’ medical history, social determinants of health, living situation, personal journey throughout this entire continuum. I’m very fortunate to see patients again from their teens and 20s into their 30s, 40s and beyond. I feel very fortunate to have the opportunity to know patients that maybe had signs of hypertension in their teens, which was treated and went away due to weight loss or whatever, but I look back at their history when they’re in their 30s and say, “Hey, we need to treat you with a children’s aspirin during pregnancy, because you’re at risk of having a recurrence of that hypertension during your pregnancy.”
Cardiologists are interesting because they’re standing on the back end in the 40s, 50s, 60s, and beyond, and they’re looking back at the work we’ve done as OB providers and saying, “Hey, this lady had preeclampsia, she had diabetes and hypertension, that may make her at risk for heart disease now that she’s older and we’re going to change things.”
That care continuum is reversible. We as providers of OB and the patient herself can stand at the beginning of her life in her teens and 20s and say, “My family history is this. I smoke. My BMI is that. I have this medical problem or that. It may be a problem during my pregnancy, and, oh, yes, I’m also aware that this may be a problem for me when I hit 50, 60, and beyond.” We’re really lucky because we get to prevent disease on a larger basis than the cardiologists. They’re looking backwards, we’re looking forward, but we’re using these elements, these sequences, these collections and bits of information in a patient’s life to predict risk.
Again, I am going to present part two of my case history. This is the same patient. She’s still a physician and she is 16, 17 years later in the grand scheme of her life.
Here we fast forward by 16, 17 years. She’s in her mid-40s. She has a great career, is happily married, and she has two wonderful children who adore her and her husband. Her life couldn’t be better. In addition to this, she enjoyed an excellent lipid profile. She was able to hike, exercise, she ate well, and her BMI remained perfect. Her overall lifetime risk of cardiovascular disease was about 3%. By all intents and purposes, she was a superwoman. She had no identifiable risk factors and was doing well.
One day while hiking, she had some pressure in her chest and it made her recall the conversation we had had at her postpartum visit about having an electrocardiogram at age 50. With that thought in mind, she decided that she would visit a preventive cardiologist and inquire about an echocardiogram. Her cardiologist basically felt that she was normal and that she did not require an echocardiogram because her lipid and her own personal history were perfect. However, being a physician she is, and understanding her own individual risk of cardiovascular disease, she asked him to do it.
With that, she did a stress echocardiogram. About 11 minutes later, her doctor came to her looking pale as a ghost and told her that she had a hundred percent obstruction of the left anterior descending branch of the coronary artery. She had a hundred percent obstruction of a second coronary vessel, and he frankly didn’t understand how she was walking. She being a physician understood that the implications of the LAD being blocked were that she could die from a sudden heart attack. She underwent stent placement, and that was quite successful. In the interim, after her successful stent placement, she came in and disclosed all of this to me.
I invited her to have some new testing, which she hadn’t had in the past, and it was something that I had been doing on my pregnancy loss patients. Again, we did a series of tests in advanced cardiac screen, and we found that she had another thrombophilia or a biomarker called lipoprotein (a). It is thrombogenic, it causes calcium to occur in the heart, and it also has been associated with atherosclerotic heart disease. She’s pretty happy nowadays because she never miscarried, she never had a heart attack, and she keeps her family well informed of what has gone on with her.
My patient here demonstrates that she’s actually the poster child for prevention. She never miscarried, never had a heart attack, and is able to look forward to a healthier future. She’s already had her children tested and she’s informed the rest of her family. How great is that? I don’t present this for any accolades because there are none that are needed, but this is just an example of how well things can go. I know that some things we are not able yet to prevent, but there is so much that we can prevent.
Again, I ask a question, were you aware that the American Heart Association recommends that all adults older than the age of 20 have their cholesterol and their traditional risk factors checked every four to six years? Most patients are not having that done. Even when they come in for IUD insertion or birth control pills or Gardasil injections, they are not having these things done. And so there’s nothing to trigger the conversation and nothing to encourage the patient. If they’re overweight, the doctor says lose weight, but it shouldn’t be a simple statement because the body is complex. We need to make recommendations like this to our patients, starting at a very young age.
Even our friends, the rheumatologists, as you can see, will say preconception counseling requires risk assessment. We’re looking at the risk of possible maternal and fetal risk, screening for biomarkers, with predictive values for adverse pregnancy outcomes. Then an adjustment of therapy, and then a schedule of monitoring, and then a follow up for pregnancy. I would add postpartum and for the rest of the patient’s life.
Rheumatologists, endocrinologists, cardiologists are all coming up with specialty recommendations for patients, but we who are the providers of primary care for OB are not taking that opportunity to impart that knowledge to the patient. It’s, come in, you want birth control pills or IUD, we’re going to do that, and, “Thank you. Next.” We need to stop that mentality.
In regards to my patient that I presented, she wasn’t quite there, but she was getting close to what I call the grand convergence. Most patients that I see are having their babies in their late 30s and 40s. In the 1940s and ’50s, and earlier than that, women had their babies in their late teens and 20s. The thought was, “Well, if they have a miscarriage, they can get pregnant again,” which was a bad thought then, and it’s still a bad thought, but we’re still practicing that way. The window of opportunity slams quickly in the late 30s and 40s. Again, we don’t want to take away that opportunity to have babies to women who want to have it. We have to identify these problems as soon as we can.
The challenges we face at the time of what I call the grand convergence is that we have older patients. Many times they’re menopausal, and that just simply means that time period between 35 and when their period ends. There’s a myriad of different things. Longer menses, shorter menses, PMS, all sorts of things that are going on. We give it a name, perimenopause, but there are hormonal changes that we’re seeing even then, even though they’re still having their menses. We also see, at that time, an increase risk for complications of pregnancy and increasing risk of stillbirths and miscarriage.
Along with that, we see an increased risk of having high cholesterol. We’re seeing elevations of lipoprotein (a), which is another biomarker for hyperlipidemia and other conditions are beginning to show their faces. Thyroid disease and insulin resistance and so on. There’s a myriad of different things that we’re beginning to see at that time. It behooves us to identify those problems as soon as we possibly can, and ideally in the preconceptual period.
For my last video, I’m going to talk about the risk cascade.
When evaluating our patients prior to pregnancy, we want to look at risk enhancers that can cause problems during pregnancy, such as obesity, hypertension, diabetes, polycystic ovarian syndrome. Lifestyle issues, such as smoking. Autoimmune diseases, thrombophilias. Poor reproductive history, such as failed IVF, miscarriage, and stillbirth.
The reason we look at these risk enhancers is that they can have a profound cascading effect during pregnancy. First, by causing placental dysfunction, damaging the blood vessels of the placenta or the inner lining endothelial layer, impairing hemodynamic adaptations, or decreasing blood flow or perfusion and causing inflammation at the level of the placenta.
This in turn is thought to cause or be some of the cause of adverse pregnancy outcomes, such as preeclampsia, gestational hypertension, growth restrictions both early and late, and of course stillbirth and miscarriage. Additionally, these pregnancy outcomes that are adverse, are thought to be indicators of future cardiovascular risks, such as cardiovascular disease, stroke, heart attacks, and blood clots, which can leave our patient totally incapacitated.
At this point, my proposal is that we want to think about newer ways of using prevention to really affect patients’ outcomes, whether it’s during pregnancy or in later life. I always like to tell my patient, my job is not to just get you pregnant, but to see through the pregnancy and have a happy, healthy baby and happy healthy mom, not just then, but for the rest of her life. We want that continuum of care present in the patient’s life.
That starts with what I like to call PREVENT. First, the P is preconceptual counseling. We want to get those patients in as early as possible. Even if they’re not planning a pregnancy, it’s never too early to discuss potential complications of pregnancy in their 20s or later teens if need be. If patients are anticipating having babies or even if they’re not, the discussion should be made. Particularly when patients present themselves to you, just asking a question, “I just got married. I think I want to have a baby.” Preconceptual counseling is essential.
At that time, you want to have them have a recollection. You want to know about the family history. You have to question them, and you really have to say, “Well, if you don’t know, can you ask your mom, ask your grandmother, ask your dad.” If they’re adopted, you’re going to change your course here, because you’re going to have to do a little bit more for those patients, because they may not have any information, but you want their past personal history.
If they have no history, no medical concerns, if they’ve been pregnant, you want to know about their pregnancies. “Did you have a miscarriage? What was the cause? Have you had a poor pregnancy outcome? Have you had a preterm labor? Have you had a low birth weight baby?” You can’t just say, “She had a full-term baby.” I’ve had patients who’ve come in and the doctor said everything was okay, and she had a 5-pound baby at 39 weeks. There was something going on. It wasn’t a petite person, there was something going on. We have to ask those questions of the patients and trigger their memory.
We want to do a physical examination. You never know what your physical examination is going to reveal. Sometimes we find thyroid problems. Sometimes we have problems of BMI. We want to examine the patient physically to make sure that there are no major concerns.
The next would be vaccinations. You want to make sure that their vaccinations are up to date. Rubella, varicella, rubeola, you can test them early to see if they’ve had exposure to parvo or cytomegalovirus. I often do that with nursing staff or physicians so that I know where they’re starting. If they’ve never had an exposure, I can tell them, and I know how concerned to be if they call and they say, “Oh, my friend’s baby has this disease and I was exposed.” We can do those things early.
Evaluate and multidisciplinary referral. Again, we want to communicate with our specialists. We want to evaluate to know when we should refer those patients. And we want to set up a plan with those doctors for how to care for the patients during the pregnancy. I have patients who have MS, and I will speak with their neurologist and she can take this medication, or she can take that medication. She can stop this. When should we start this? We want to collaborate with them at that time.
Nutrition. Diet and exercise goes without saying. If patients are overweight or underweight. If they suffer from anorexia, you want to get them on the right track as best you can prior to pregnancy. Again, we need to have this conversation and stress those things with the patients beforehand.
Finally, the T in PREVENT is testing. Again, as was suggested earlier by the American Heart Association, if they’re over 20, you want to get their lipid screen. You want to do diabetes testing, thyroid testing, genetic testing. Far too often patients come in already pregnant and we offer them screening for the genes for cystic fibrosis, spinal muscular atrophy, Tay-Sachs and Fragile X because we’re supposed to, but patients may or may not accept those at that time. Even though we tell them we’re testing them, it doesn’t feel quite right to them because they always feel like we’re testing the baby. It’s best if possible, to get those tests beforehand.
Included in our genetic screen, we also slip in some thrombophilia testing for Factor V Leiden and prothrombin. There are a few other tests that we’ve put in because it doesn’t cost anymore to test that one gene or 500 genes. We’re currently doing four genes tests beforehand if we can get the patients in.
The S is just an additional, it’s surveillance, and this is important for when the patient is already pregnant. We want to look at simple tests. One of the simplest things we can do is a placental volume. Dr. Kliman from Yale invented the placental volume, and it’s a really easy test. We do it in our office. You can do it as early as 12 weeks. If the baby’s placental volume is less than the 10th percentile for growth, then we simply are suspicious for possible future intrauterine growth restriction, stillbirth, et cetera. It makes us aware and we can step up our surveillance.
Biophysical profiles are another way we surveil the patient. Looking at ultrasounds with dopplers of the middle cerebral artery and umbilical doppler and doing non-stress tests. Don’t be afraid to do those and do them regularly because the worst thing that can happen is that you will find something and make that referral out to the perinatologist. It’s important to look.
One very disheartening thing I see currently is that a lot of patients are started on children’s aspirin empirically without knowledge, without testing beforehand. They don’t know if there’s any genetic testing, they’re just saying, “You’re over 40. Here, take this.” Yes, it helps to prevent preeclampsia, we do know that, but a funny thing happens is that it’s suggested that we stop aspirin at 36 weeks. Those patients at 36 were taking away something that we were giving them. My opinion is that surveillance should increase at that time, not go away or not be nonexistent.
If I have a patient that is coming off a treatment that has been sustaining the pregnancy nicely, when I stop that treatment, I increase my surveillance. I don’t decrease the surveillance. Looking at all of these things together is really about caring about what goes on before the patient is pregnant, during the pregnancy, and really having a forward view for a lifetime of good health for the patient.
With that, I will end. I will say, thank you. My final words are, “So I heard you two finally tied the clot.” “Sure did,” “Coagulations.” Thank you very much.
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