Human Genetics Analysis

Every day in the office I deal with the issues involved in human genetics. Making a human baby involves the union of the genetics of a mother and a father. A man and a women. Benjamin Franklin (one of the American Founding Fathers) used to like to say that only two things in life are certain. They were, in order of importance, Death and Taxes. Americans repeat that phrase often. We usually say it fast without any pause in between.  I would add that there are a few other certain things in life. At the beginning of life, there is Birth. One cannot have a death without having a birth. There is a Franklindian certainty (of the Death and Taxes type) that a human being must have one genetic mother, to be born. One mother must provide the genetics. Every person who is born has one genetic mother.

Similarly, every human that is born has a genetic father. 

What are genes? They are the information storage system of all known life. The DNA system is astonishingly the same for all known life. The Scientists Watson and Crick received a Nobel prize for discovering that the genes live on a helical molecule called DNA. Deoxyribonucleic Acid.  They discovered it in the 1950's.  A normal structure of the DNA molecules in a living human cell is for each of these molecules to be coiled up into Chromosomes. An uncoiled DNA molecule is several meters long. Coiled up, 46 of them fit into the nucleus of a cell, and the chromosomes are millions of times shorter. Chromosomes are easily visible under a microscope. I see pictures of actual human baby chromosomes all the time. This is the end result of a genetic amniocentesis. A normal cell has exactly 46 chromosomes. 23 chromosomes come from the mother, via her egg, and 23 from the father, via his sperm. The woman always contributes 23 chromosomes. Since every women (and human) has 23 pairs, or 46 total, every egg has to choose one of the pair of each 23 pairs. This has some astonishing statistical implications. For instance, each woman can make 2 to the 23rd power different kinds of human eggs. No more, and no less (unless there is chromosomal "pathology"). 2 to the 23rd is 8,388,608 different kinds of human eggs for each woman. Each human woman is born with about 300,000 human eggs. They are created before she is born, and she will create no more during her life. Statistically speaking, every one of those 300,000 eggs is completely different, genetically and chromosomally unique. The odds of any two eggs having the same chromosomal material is about one in 8.4 million. The odds of there being two identical eggs in a woman, out of her whole complement of 300,000, is about one in 28. This is 8.4 million divided by 300,000. 

The statistics for sperm are exactly the same, but for the fact that men make trillions of sperm throughout their life. But they can only make 8,388,608 different kinds of sperm.  

How many different kinds of human siblings can a specific man and women make? This is an easy statistic. It is, choose one of the different kinds of eggs, and choose one of the different kinds of sperm. The math is 8,388,608 times 8,388,608. Equivalently, 8,388,608 squared. This equals 70,368,744,177,664. Not one more or one less. Lets just call it 70 trillion. So a couple would have to have about 35 trillion children before they had a 50 percent chance of having genetically identical children. Obviously identical twins are much more common than that. The reason there are more identical twins is because the human embryo sometimes splits into two or more, before the third day of conceptional life.  

Therefore, chromosomally speaking, it is vanishingly unlikely that any two humans have anywhere near the same identical chromosomes, unless they are identical twins. 

And unrelated humans have even less likelihood of having common DNA. 

If a single family can make 70 trillion different kinds of offspring, then how many genetically different kinds of humans can be made? It boggles the mind. 

There are a lot more interesting genetic facts and conclusions. 

Lets get started with some more interesting analysis. 

Everyone has two of the first chromosome, called chromosome number one. It is the largest chromosome, so it contributes a lot of genetic material. Everyone gets one from their father, and one from their mother. The one they got from their mother is a genetic identical copy of her mother's. And the other is an identical copy of their father's first chromosome. Her mother got one from her mother. And her mother got a perfect copy from her mother. And so on and so on. The only changes that exist are "mutations". Mutations are spontaneous changes in genetic material that happen when a child gets a different chromosome that their parent had. Mutations happen because of an error in the copying mechanism that creates cell division. They might happen, for instance, when a gamma ray hits the chromosome and changes it. Or when the wrong biological molecule gets stuck in the copying machine. 

Mutations happen at a statistically predictable rate. Most mutations are "bad", but some are favorable. Mutations are important because they are one source of genetic evolution. The other, more important source, is simply which chromosomal rearrangements of the 70 trillion possible, are "better"? Which one makes a human smarter, bigger, stronger, more resistant to disease, etc? Which one will survive, and therefore survive long enough to make even better children? 

Because we know how many mutations there seem to be, we can extrapolate backwards in time to a genetic "Adam and Eve", that was the first set of humans. Genetics professors have done this, and have decided that the first human tribe consisted of about 40 human females, or "Eves", and they existed about 200,000 to 250,000 years ago. Most likely this tribe was in North Africa, and spread out from there. Since then the human species has grown in number. Most of the growth is recent. There have been about 120,000,000,000 humans born since then. 120 billion. The reason I say Eves and not Adams, is that it is easier to do these statistics with women, because of some genetic implications of the mitochondrial DNA, which is a different set of DNA, and only comes from the mother. 

A similar analysis has been done with the "Y" chromosome, that only comes from fathers, and the fathers father, and his father, and so one. 

The fossil record, and anthropology, is consistent with the human species being this old. All of recorded history begins about 8000 years ago. But we know that modern human culture, with words, art, tribe hunting, of large and dangerous game, and oral histories, began at least 50,000 years ago. 

Anyway, I was looking at a photograph of human chromosomes today, with a new patient to the practice, and she had a bunch of really interesting questions to ask. She had already had a genetic amnio, and this was the report on the baby. The baby had normal looking chromosomes. The baby had 23 pairs of human chromosomes, labelled 1 to 22. All of them looked normal. There were two X chromosomes, and no Y chromosomes, so we knew it was a girl. 

One of the most common abnormalities of the amnio result is a triplication of the 21st chromosome. This is the second smallest chromosome. Somehow, when a sperm or egg is created, the chormosome sorting machinery goes awry. This means an egg or a sperm gets an extra chromosome This means that this human fetus would have trisomy 21, or Down's syndrome. Down's is quite common. It is not a mutation. A 35 year old women has a one in 300 chance of having a Down's baby. A 40 year old has about a one in 30 chance. It is much more common as a women gets older. 

There are trisomies of all the chromosomes. Most are incompatible with human life, and never create pregnancies. Trisomy 21 is  one exception in that these pregnancies create a human with Down's syndrome. Trisomy 13 and 18 do create pregnancies, but the fetuses never survive more than a few days of life, if they even get to full term. They are highly abnormal. On the other hand Trisomy of the X chromosome is much less abnormal. In a female with an extra X chromosome, she is completely normal. It will likely even never get diagnosed. Even her children will likely be normal. Men with an extra X are called Klinefelters. They are tall, they are tend to have weak muscles, they may have an emotionally tough puberty, and they don't make sperm. So they cannot have their own children. Trisomy of the Y is called XYY. These are normal males. The teaching used to be that these boys were troublemakers, had high testosterone, and wound up in prison a lot. More modern thinking is that they are about 3 inches taller than usual, and about 5 IQ points smarter than average. They are basically normal people, like the XXX females are normal. 

Finally, I would like to say that that the scientific quantity of knowledge in the field of genetics is exploding. There is so much to know about genetics analysis of individuals, and their children, and the means of inheritance, that it is literally impossible to keep up with current knowledge, recommendations, and the science. I have spoken with our genetics consultants, and I am continually surprised by the new genetics testing that is possible. And these possibilities continue to expand. The geneticists themselves have to frequently hit the books to figure out any individual case. 

Myself, I frequently refer to geneticists because there is just too much to know. 

There are a couple of advancements to note, though: 

About 1990, the US Federal Government funded the genetic sequencing of an individual. The cost to do this was about 3 billion dollars. The wikipedia page is here: http://en.wikipedia.org/wiki/Human_Genome_Project 

The first draft of the genome was printed about the year 2001. 

Now, the cost to do the sequencing continues to decrease. 

There is a report of a company that can do an individual's sequencing using "system on a chip" technology borrowed from the computer industry. This company claims to be able to entirely sequence a human for about a thousand dollars. I reported about this in a prior blog post. 

Right now it costs my patients, or their insurance companies, about 3 or 4 thousand dollars to test for a few breast cancer genes. Do the math and you will  see that the cost of genetics analysis will continue to plummet over the next few years. 

Also, the Genetic Amniocentesis may be going to way of the dodo bird. I mean, it may be going extinct. Or, it is going to become increasingly rare, and used only at the end stage of a diagnostic workup. Women hate doing the amnio because it pokes a needle very near their baby. And it has a miscarriage risk quoted to be somewhere between one in 300 and one in 1500. Nowadays, I can order a simple blood test that can tell me if the pregnancy has a trisomy 13, 18, or 21.  These are the most useful trisomies to test for. The one that I do in my office is the Materna T-21 test. I recently ordered it for a pregnant women who was found to have a downs risk of about 1 in 350. In the past, this women would have faced a very difficult choice between risking the amnio, with it's inherent risks, or risking the Down's, with a risk of about one in 350. Technically, her Downs risk was completely normal, because we don't call it elevated risk until the risk is about one in 300 or more. But, in this day and age, where a common Down's syndrome risk assessment is one out of a quarter million, I don't see how couples are going to be happy living with a risk of Down's of one in 350 when I can do a noninvasive nearly risk free amnio alternative. 

We can only hope that the insurance companies will pay for the noninvasive modern T21 style tests. I think they will ultimately come along and pay for it, but it will take some time and work to convince them. 

Thank you for reading my blogs. Comments are very welcome. 

Dr John W Marcus MD FACOG PC 

89 North Maple Ave 

Ridgewood, NJ 07450 

Phone 201-447-0077 

Fax    201-447-3560 

Blog at : Http://doctorjohnmarcus.blogspot.com/ 

Please send your friends to read here as well. 

Hyperemesis Gravidarum, or super vomiting  of pregnancy. 

Right now our beloved Princess Kate is hospitalized with Hyperemesis Gravidarum. 

The royal spokesperson has said that she is less than 12 weeks pregnant, but has not given us her due date yet. We can assume that she is past 8 weeks or so, or the HG would not be at this stage. So she is between 8 and 12 weeks. That means she is due near July 1st 2013. 

HG happens when the pregnant women is so nauseous that she vomits nearly continuously. 

Nausea and Vomiting are completely normal parts of the first trimester of pregnancy. Most women will experience some of this. In fact, most women will lose some weight the first trimester of pregnancy, just because they cannot eat a lot of food. 

But, when a women suddenly gets so sick that she cannot tolerate fluids, and what fluid she does have vomits back up, two bad things will happen. First, she will get severely dehydrated. And that will make her very very weak. Her blood pressure will be low, and she may not have the stamina to even get out of bed. The second bad thing that happens is that she will lose electrolytes, such as sodium, potassium, and chloride. Losing the electrolytes is worse than plain dehydration because it can make the heart beat irregular, or worse. 

We can detect this severe dehydration by weighing the patient. If she loses 10 pounds over a few days, then she has certainly lost enough fluids to go to the hospital. There, we can replace the fluids and check the electrolytes. 

Obstetricians don't really know what causes such a severe intestinal problem. We know that progesterone, which is a hormone that the ovary and placenta makes in abundance, can make people sick. Some women get really bad PMS from the natural progesterone of a normal menstrual cycle. The progesterone peaks about day 23 or so of a normal 28 day cycle. A lot of women feel awful from that peak of progesterone. It makes their breasts sore. It retains fluid. It makes them crabby. It makes them gain a few pounds of fluid. It makes their intestines fill with gas, and they get really bloated. They really hate it. The peak progesterone level of a normal cycle is about 12 or so, according to my lab.  In pregnancy it may go up to several hundred, as the placenta makes a ton of it. The natural purpose of the progesterone seems to be to keep the uterus from having a menstrual period, and thereby pushing the baby out. The uterine muscle responds to the progesterone by getting very soft and dilated. Unfortunately, that same kind of muscle is in human intestines.  Under the influence of that much progesterone the intestinal muscles seem to dilate and get soft. This prevents peristalsis and makes the women nauseous as the food backs up into the stomach and esophagus. 

There is also a strong belief among some people that the nausea has an evolutionary purpose. 

What I mean is that the vomiting may be a defense mechanism to protect the fetus from noxious foods and exposures. This is because the first trimester has an importance unlike any other time in human events. It is the phase of organogenesis. 

The first trimester of pregnancy lasts from about 2 weeks of pregnancy (that is before the pregnancy is even known about) until about 13 weeks. The first trimester has an unbelievably important function for the fetus. It is the phase of "organogenesis". This means that the baby is actually forming it's own anatomy. The heart is being built into chambers, the kidneys are being made, all the tissue layers are folding into final position, the basic brain structure is starting up, and all of the events that create a human being are happening. After 14 weeks, all of this complicated tissue construction is done. The only thing left is to grow and fine tune the functions of the organs. 

What is the last organ to be completed? I like to tell my patients it is the brain. That is done, in some people, around the 40th year of life or so. There is a bit of humor and a bit of truth in that statement. It is my belief that the human brain never stops developing. Since we can all learn new things, and do new activities, it seems to me that the brain never stops growing. For this reason I believe in lifelong "effortful" learning. Effortful is the opposite of Effortless. For this reason, I like to say that people should push to learn and do and experience new things all the time. For me, my recent activities include learning to play the guitar, learning languages, and learning new computer processes. Such as learning how to write a blog on Google, learning the Java programming language, expanding my knowledge of Pascal, keeping up with the latest Basic compiler from Microsoft, and things like that. 

And to grow the brain we have to nourish it. That is why I recommend everyone including myself to take DHA omega three supplements. This is an essential fatty acid component of human brains, that no one gets enough of, that cannot be created inside of a human. I take and recommend 300 mg a day of DHA. 

Probably the second to last organ to be finished is the lungs. I don't know why, but the human lung has a lot of trouble oxygenating a human being until about 36 weeks of pregnancy or so. There are multiple issues with the function of an immature human lung, but one of the last factors to be created is Surfactant. The NICU now uses artificial surfactant and that helps the premees quite a bit. It helps them breath. 

But, until all of this complicated organogenesis is done, there is a very delicate fetus. If there is some unfortunate exposure to a toxin of any sort, it may have a disastrous effect on the organogenesis. The heart may not form right. The cover over the spine may fail to fuse, causing anything from a spina bifida to anencephaly. There may be entire limbs missing. There may be a tiny imperfection, like a cleft lip. There may be a huge central failure, like syrinomelia, where the legs are fused. This is why most physicians are loath to prescribe any medicines in the first trimester. We will, if possible, defer any medical treatments to the second trimester. Sometimes, we will defer treatments of minor infections. We will push hard to defer X-rays, if possible. We will certainly advise against smoking, drinking, and illegal drugs. We do not advise refraining from exercise or sex, unless there is a specific reason to do so. 

So, some people believe that Hyperemesis is Mother Natures way of protecting the fetus from noxious exposures. Most pregnant women will run away from any noxious fumes, because it makes them extremely nauseous. This serves a very important purpose of keeping those toxic fumes away from the baby. 

As an obstetrician, my job is to keep the baby safe. Keeping the baby safe means keeping the mother comfortable.  

If a pregnant women has more vomiting than is safe for the baby, then we need to take action. The first thing to do is to see if dietary modifications will help. I will ask the women to start taking a tiny sip of Gatorade every 20 minutes. This will replace the electrolytes and the fluid slowly, and prevent there from being too much fluid in the stomach as to make her vomit it back up. I will ask her to stop all spicy and greasy foods. I might ask her to have one salty cracker (called a saltine her in the USA) every  twenty minutes. Sometimes the saltines and Gatorade diet does the trick. 

Sometimes we try the BRAT diet. This is bananas, rice, apples, and toast. This diet is explained on Wikipedia page here: http://en.wikipedia.org/wiki/BRAT_diet. 

If the women needs medications to stay hydrated, then we usually start with phenergan and or odansetron (Zofran). If pills get vomited, then go to suppositories. Women don't like that of course. If that doesn't work, then go to IV or Subcutaneus pumps of these meds. Plenty of women are maintained on these meds, sometimes they need them for most of the pregnancy, if the situation is really bad. 

If nothing else works, then the women needs both IV fluids and IV nutrition. These IV's can save both the mother and the fetus, and I have managed this many times. Most of the time I will ask for the help of a specialist in IV nutrition. Our hospital has several of these specialists available. I call them into the case, and their help is very much appreciated.  

Sometimes, in bad cases, such as if the gallbladder goes bad at the same time as Hyperemesis, these women will need IV nutrition for the whole pregnancy. It is certainly possible. These women are really suffering, though. 

If the vomiting is not managed well enough, then the stomach acids can inflame the esophagus  This can get really painful, and needs to be managed as well. These stomach acids are really bad for the teeth, too. Just like in a bulimic patient. 

Let's hope that Princess Kate doesn't need this kind of service, but if she does need it, I am sure that it can be provided. 

Thanks once again for reading. 

Dr John W Marcus MD FACOG 

89 North Maple Ave 

Ridgewood NJ 07450 

phone 201-447-0077 

fax 201-447-3560 

blog at doctorjohnmarcus.blogspot.com 

comments below are very much appreciated. 

Stem Cells


Everybody asks, "Should I have my umbilical cord blood stem cells frozen and stored?" Usually, by the time patient is asking me this question, she has been bombarded with advertisements from the stem cells storage companies. But, even if the patient doesn't ask me, I will ask the patient at about 20 weeks. In my practice, it  is a prenatal care checklist item for 20 weeks, along with the 20 week genetic and anatomy sonogram. So, I will make sure that the patient has the information that she needs to make a good decision.

First of all, everybody should be aware that umbilical cord stem cell storage has not been endorsed by any professional group other than the stem cell companies themselves. My ACOG states that this procedure is unnecessary. Anything that is unnecessary is not going to be a covered benefit under the health insurance. So, anyone who does it is going to have to find a way to pay for it.

It costs anywhere from $1350 to $9000 or so to get the process started. The price varies from company to company. There is also variance on what exact services you have contracted for. There are some companies that will take the whole placenta and use it to get more of the stem cells. Other companies will take a short segment of the umbilical cord itself. All of these things are added cost.

Once the stem cells are frozen and kept under liquid nitrogen, the companies that do this work will charge you once a year to keep the cells frozen. The yearly charge is something on the order of 150 to 250 dollars a  year. I suppose that if you don't pay, they would throw out the stem cells. Or maybe donate them to science, or a public stem cell bank.

What is the benefit of doing this?

The stem cells that are retrieved from the umbilical cord, fetal blood, and placenta, are processed and examined by the cord blood storage companies. Then they are deep frozen under liquid nitrogen. This does not kill the cells. It preserves them for future use. If, in the future, this baby has some kind of medical problem that can be cured with an infusion of stem cells, then the stem cells are there for the baby to use. These problems are usually some kind of leukemia or cancer. In that case, the future oncologist has the option of removing this victims bone marrow cells, curing the cancer, then thawing out the stem cells, and then restoring the immune system with those stem cells. This is all only theoretical, because the successful cases done like this are rare.

The stem cell companies claim that about one out of 200 stored units are eventually put to use. I have not seen an independent validation of this claim. If this is so, then I think that everybody should do the stem cell storage. I think it is more likely that there is a small number of stem cell units that are used. The rest will stay frozen indefinitely.

There is a ton of ongoing research right now to see if stem cells can be used to treat a bunch of other conditions. There is some some studies being done for heart disease, and some even on autism. So the applications for stem cells seem to be widening. It may be that the future for stem cells is very wide indeed.

On the other hand, biotechnology marches on. It seems now, that many times, the biologists can get stem cells retrieved even from grown ups. If this is so, then there is no reason to store the fetal cells, as everyone has stem cells. We can use the adult stem cells to do the job of the fetal stem cells. If that is true, then no one needs to freeze the fetal stem cells, we have our adult cells and that will be good enough.

So, in the final decision making, a family needs to decide the odds of using these stem cells, versus the odds of not using them or not needing them because the body makes it's own. I also tell my patients that if they need the stem cells years later, and they didn't store them, they may be very sorry.

And then the decision is affected by how much you value the 2000 dollars or so you invest in it.

I tell a family, "if you have a lot of money, then you can spend a lot on the stem cell fees". On the other hand, "If you don't have a lot of money, and 2000 dollars will break the bank, then don't do it. Either way, I will help you both figure out the right thing to do is, and I will help you do it. You need to make your decision some time before the placenta comes out."  I will then note in the chart that we had the discussion, and I will note whatever they seem to be deciding at the moment. We will revisit this discussion throughout the rest of the pregnancy and I will offer to help decision making.

The majority of the people in Bergen County will decide that they do not want to pay for it.

If they do, there are a couple of good choices available.

Viacord is the biggest company. They are based in Ohio. They will not let you visit your unit of blood. They generally will not negotiate with you. They will provide my office with 500 dollar coupons that people can use to lower the price from 2300 to 1700 dollars.

Neostem is the best local company. They are based in the next town, Allendale New Jersey. I personally have met some of the people, and I like them. They will let you visit your unit of blood. They have good prices. They will talk to you on the phone. They also have a coupon available in my office.

CBR is another big company.

There are a hundred others.

The local blood bank still does it as well. I don't know why more people don't use them. Maybe they are being out marketed by the commercial providers? I don't think the blood bank markets the service at all. They used to have an open donation program that was free to donors. I sent a lot of donors their way. The donor program is now closed due to lack of money. As you can imagine, the donor program was quite expensive to administer. If it ever opens again, I will send a lot of patients to the blood bank for stem cell donations. It was a very very popular program with my patients when it was still open.

Ultimately, the decision to store the stem cells is difficult for most people. It is an assessment of risks, potential benefits, and costs.

Sometimes, the grandparents have a very strong opinion, and take action. It's great watching them when they do this. It becomes a parent taking care of a child, but the parent is the new grandparent, and the child is the pregnant women and her husband. The grandparents say, "where doing this, that's all their is to say about it". They will allow no dissent. And then the stem cells are stored.

I don't know how the stem cell companies find the pregnant women to market to, but they seem to use some kind of internet magic. There was a story of a 17 year old girl who got pregnant, and did some looking around the internet on Google. Pretty soon, there were items in her mail box to help her with the pregnancy, and try to sell her things. This, despite nobody but her knowing about the pregnancy. Her Father read the mail, and found out she was pregnant. I don't know the outcome of that story. There is a strong lesson there, though. The lesson is, almost nothing one does is the modern world is completely private. I think, for the sake of safety, always assume there is a camera watching you, and there is someone who knows what you do on the internet. There are technical ways to block that snooping, but I am pretty sure they are not completely successful at blocking your trail.

I think the next post will be about Hyperemesis Gravidarum, as that is what our beloved princess Kate is hospitalized with right now.

Thank you sincerely,

John W Marcus MD FACOG
89 North Maple Ave
Ridgewood NJ 07450

phone 201-447-0077
fax 201-447-3560
blog at doctorjohnmarcus.blogspot.com

Pre-eclampsia or Toxemia

Toxemia is a big problem.

Toxemia strikes about one in twenty pregnant women. It is usually mild, but sometimes is severe. Occasionally it will become life threatening. When it gets really bad, it develops into eclampsia (instead of pre-eclampsia). When it is super bad, it leads to a failure of the blood systems, then we call it HELLP syndrome. HELLP is an acronym for "Hemolysis, Elevated Liver Functions, and Low Platelets". About one out of 75,000 pregnant women will get toxemia so bad that they die of it. 

The professors of Ob all call this pre-eclampsia. The old folks will likely call it toxemia. Personally, I like to call it toxemia. I think the name toxemia better reflects an understanding of what the disease process is. The old latin name of pre-eclampsia just doesn't create any useful meaning to me. In any case, all physicians know both meanings. 

To put the mortality rate into perspective, there are about 5000 hospitals in the USA. This means that about 1 in 15 hospitals can be expected to lose a patient to toxemia in one year. And about one in 20 Obstetricians will lose one patient in his or her's entire career. This is assuming an Ob career involves about 5000 babies. Personally, I have already delivered more than 5000 babies, but I believe I have more experience than most. 

Some hospitals have more high risk cases. Those high risk hospitals will obviously have a much higher count of the risky cases. 

My hospital, The Valley Hospital in Ridgewood NJ, attracts these extremely high risk cases. We have one of the best Neonatal Intensive Care Units in existence. Our chief neonatologist is Dr Frank Manginello. He is a noted author of one of the best NICU reference books in existence. His best selling book is called Your Premature Baby. The book is available on Amazon. Here is the Amazon link: http://amzn.com/0471239968 . 

We also have a superb IVF program, and a wonderful Maternal Fetal Medicine team, not to mention a medical staff in the thousands, most of which were trained in New York City. Many of them maintain privileges at University hospitals. 

For instance, my favorite fetal cardiologist is Dr Zvi Maran. He has privileges at both Valley and at Columbia University. Columbia is about 20 minutes away just over the George Washington Bridge. Dr. Maran took care of my daughter when she had a very frightening cardiac arrhythmia. He and his excellent partners got her through this and eventually her heart healed itself. 

So, hospitals with a higher risk population is going to see a lot more of the riskier cases, and their experience is going to be higher than just the numbers will show. 

What is Toxemia? 

Nobody really knows for sure. But, even though we aren't sure what it is, we do know an awful lot about what it does. The body of the pregnant women is behaving as if there were a really bad toxin in the blood stream. No toxin has ever been found. But all of the organs start to fail. First, the blood pressure starts going up. This is due to the arteries feeding these organs squeezing down on the blood flow, leading to less flow to these organs. Early on, the kidneys start to malfunction. The kidneys start making less urine. This leads to fluid retention and severe swelling, and usually 10 pounds or more of fluid is retained all throughout the body.  The kidneys start to "spill" protein into the urine. There is usually no protein in urine because the kidneys are good at making clear urine and keeping the valuable protein in the body. In toxemia the protein spills out. 

So a lot of prenatal care is designed to check for these things. In a prenatal visit, the blood pressure will be checked, the patient will be weighed to see if there is this sudden severe fluid retention, and the urine will be checked for protein. All of these checks are to test for the signs of toxemia. 

Officially, the diagnosis of toxemia requires an elevated blood pressure, and some protein in the urine. 

The brain will eventually be affected. Some of the signs of toxemia affecting the brain are: a bad headache, visual changes including dark spots, sparkles, blurry vision, loss of vision, or more rarely, personality changes. 

The liver will be affected some times. This will lead to an elevation of the "liver enzymes" on a comprehensive panel of blood tests. If the liver gets too swollen, it can cause pain in the liver area of the abdomen. This is considered the right upper quadrant of the abdomen, just under the lower edge of lowest rib. A very swollen liver can actually rupture. If this happens, the patient may die from the blood loss into her abdominal cavity. I have never seen a liver rupture, but I have seen many many painful tender livers, with elevations of the liver blood tests. This is all quite common if toxemia gets to the HELLP stage. 

In the blood, the red cells can rupture. This can lead to severe anemia, and elevations of bilirubin in the blood on tests, and bilirubin in the urine as well. Also, in the blood, the platelets can get used up by the toxemia, leaving the platelet count perilously low. These women may need platelet transfusions.  Platelet transfusions are easy to order from the blood bank, and can be lifesaving If the platelet count gets too low, a life threatening hemorhage becomes likely, especially at the time of delivery. At delivery a woman needs all the platelets she has to shut off the blood flow to the placenta. Without that, there will be a hemorrhage. 

The blood flow to the heart muscle can be compromised, leading to heart failure, or a heart attack. 

All of the organs can be compromised. 

None of the toxemia directly affects the baby. Only to the extent that toxemia affects the mom or the placenta. 

If the blood flow to the placenta is compromised, then the baby may become short on oxygen, or may be short on nutrition. The baby may stop growing. The babies blood pressure may become very low. 

The placenta might even disconnect from the mother. If this disconnection is more than a mild case, then the baby will be distressed or even die. We call these placental disconnections Abruptions. Placental abruptions are much more common with hypertension, than will normal blood pressure. Abruptions can also happen from some kind of trauma to the pregnant uterus. Car accidents, falling over on ice or on the stairs, or physical assault on the fetus, can all cause the placenta to abrupt. A complete abruption when a woman is far away from the hospital will almost certainly end the babies life, and will very much risk the mothers as well. Sometime the blood just pours out of the vagina like a hose. If this happens there are only a few minutes, perhaps 10 but maybe up to 30 minutes, to try to save the baby and the mom. I have seen many abruptions. If it happens in the hospital it is almost certain that we can save the mom and the bay. If the private obstetrician is not there with the patient, then we have the on call ob. The "doc in box". In my years doing the on call, I have saved maybe 4 or 5 or more from a placental abruption. Mostly by doing a really fast C-Section. 

After the baby is delivered the nurses will sometimes come up to me and say, "thank you for coming right away when I called you. You saved this baby". My answer to that is, "no, you saved the baby by being there, recognizing the problem, and calling me without delay. You saved the baby, I was just doing my job". In the end, doing our jobs requires a lot of teamwork. Everyone becomes a link in this chain of human events. And when it all works out, we can all be really proud of what we do. 

But not all abruptions are complete. Many are partial. It is easier to save those babies. 

How to diagnose it? 

If the blood pressure is elevated, then we know there is a problem. It might be "gestational hypertension", which used to be called PIH, or pregnancy induced hypertension. Or, it might be toxemia. We will look for protein in the urine, either on a urine dip strip or on a 24 hour urine collection. We will order blood tests to look for hemolysis, low platelets, and liver function tests. We will likely need to do these tests in the hospital. The patient may be formally admitted, or she may be kept as an outpatient for up to 24 hours. 

We will ask her if she has a headache, or visual changes, or sudden fluid retention and swelling, We will ask her about nausea, and pain in the liver area. 

We will weigh her, examine her lungs, heart, liver, and uterus. We will check the reflexes. If they are elevated, that is a sign of toxemia. 

If the blood pressure is below 160/100, and there is no hemolysis and the platelets are normal, and there is no liver involvement, and no brain involvement, then we call it mild toxemia. Mild toxemia remote from full term can be observed, usually in the hospital, but sometimes at home. Mild toxemia at term should be delivered without delay. 

Delivery cures toxemia 100 percent of the time. If the women has permanent damage to her kidneys, or heart, or anything else, as result of a terrible toxemia, then those problems can last forever. But the toxemia itself will be gone. usually it fades away from hours or days after delivery, and is completely gone in 6 weeks time after delivery of the baby. 

A patient with severe toxemia will need to be delivered regardless of the gestational age. Even if it means losing the baby. We have to deliver the woman, even at 22 weeks, and sometimes deliver a non-viable baby. If we do not deliver the baby, then the mother may die or be permanently damaged from the multiple pathways of pathology I described above. We do not want to have a maternal mortality. 

Even having said all of that, ACOG (American College of Ob/Gyn) has written a recommendation that some milder cases of severe preeclampsia, if they are remote from term, may be allowed to stay pregnant a little bit longer if it means the difference between life and death for the fetus. ACOG will only allow this protocol under certain circumstances. Among them are an experienced facility with very experienced Obstetricians, perhaps with Maternal Fetal Medicine specialists available. Our facility fulfills all of those criteria. Therefore I am comfortable managing a "moderately" preeclamptic patient without immediate delivery. But in most cases, immediate delivery is necessary. 

Who is at risk? 

Some women are much more likely than others to get toxemia. Hypertensive patients, diabetics, older pregnant women, over stressed women, women who have had it before, women who use drugs like cocaine, women without prenatal care, women who suffer from poverty or who don't have a family or husband to help, women with anxiety disorder. 

But even so, it can happen to anybody at any time. 

Prevention? 

Many things have been tried to prevent toxemia. Nothing has worked. We can certainly prevent some of the risk factors, though. We can provide proper prenatal care, proper nutrition, prevention of diabetes, lower lifestyle stress issues, prevent drug abuse, and engage the family into a social support group. 

Aspirin has been tried and it doesn't work. 

Calcium, magnesium, vitamins, none of them work. 

We usually advise some moderate bedrest to lower the blood pressure, but most Obs don't believe that bedrest will actually prevent it. And bedrest itself has a number of severe risks, especially including lethal embolisms from DVTs, but also including severe decondioning, which may require physical therapy to overcome. 

Someday, someone may actually find the toxin of toxemia. If they do, there will surely be a Nobel prize to that individual. 

Thanks for reading. 

John Marcus MD Ob/Gyn 

89 North Maple Ave 

Ridgewood NJ  07450 

201-447-0077 

blog at doctorjohnmarcus.blogspot.com