Preeclampsia: early disease, late consequences
Pregnancy is a joyous, wondrous, incredible, revelational time of your life. The bringing of new life into the world is a truly amazing thing. But if you think about it, even just a little bit deeper than the superficial musings that most of us have about this phenomenon you will realise that pregnancy is bizarre – just plain weird. A parasite, starting as little more than the size of a grain of sand grows within your belly until it reaches 7 to 8 pounds of size and then is projected into the world. Within, it sucks all the goodness out of you even if you’re feeling like crap (eg. morning sickness). Without, it can continue to suck the goodness out of you (potentially for the rest of your life - he says tongue in cheek).
The baby developing within your body only has half of your chromosomes. In other words, biologically half of it is alien and foreign to your immune system (i.e. comes from the father). Some of this genetic material from your unborn baby is even released from the placenta into your bloodstream – that’s how one of the newer tests for Down syndrome works – it detects the baby’s chromosomes in your bloodstream (you can read about it HERE in an earlier blog). By all rights your immune system should mount a biological assault on your unborn baby in order to rid it from your body. But it doesn’t! Your immune system allows it to thrive. It actually lets part of the baby (the placenta) grow into your body (the wall of the uterus) so that it can scavenge oxygen and nutrients and disgorge its waste products. That’s a little freaky! What’s even freakier is that the way the placenta invades the uterus is a bit like a cancer. Very rarely if the invasion process goes unchecked it can go all the way through the uterus and into the surrounding organs. Don’t flip out now – this is EXTREMELY rare.
So what does this all have to do with preeclampsia?
Well, if the process whereby the placenta “invades” the uterus goes a little cock-eyed very early on then in the pregnancy (we’re talking the first few weeks) the stage can be set for preeclampsia to develop later in the pregnancy. The exact mechanism by which this occurs is still being figured out but it is thought that abnormally developing blood vessels within the placenta cause low oxygen levels in the placenta. This sets off an inflammatory like process within the blood vessels throughout the mother. The inflammatory process in the mother doesn't usually occurs until the third trimester even though the stage was set waaaayyyy back in the beginning of the pregnancy. The end result is high blood pressure and protein leakage from the kidneys into the urine. Increased oedema in the peripheries (swollen legs) also commonly occurs in preeclampsia. However, this is also a very common benign finding in the latter stages of pregnancy.
When preeclampsia is mild, only the high blood pressure and proteinuria are found but in more severe preeclampsia the process can affect other organs systems and cause issues such as low platelets (clotting cells in the blood), abnormal liver function, abnormal kidney function and the abnormal placenta development can also cause problems with growth in the baby. In some instances the slowing of growth in the baby can be the first sign of the disease – something that is picked up even before the blood pressure starts to increase.
I'm hearing you ask – do women with preeclampsia get "sick"? what is the end result of preeclampsia? Most women with preeeclampsia don't get terribly sick. Their blood pressure remains within reasonable limits and the leakage of protein into the urine never gets very high. However, some women can become so sick from preeclampsia that they can go into multi-organ failure. Their kidneys start to fail. Their livers become inflamed. They can even have problems with the clotting systems within their blood. Yes, women with preeclampsia can get VERY sick and can end up in ICU being intensively monitored. This is uncommon. There is also a more dramatic end game to preeclampsia. You might be wondering why it’s called PRE eclampsia. There are a lot of PRE words out there where the PRE is a warning of things to come. Like PRE menstrual, or PRE meditated, or PRE term, or PRE admission. The PRE indicates that there is more to come and in preeclampsia that is – eclampsia. Eclampsia has been defined as “a condition in which one or more convulsions occur in a pregnant woman suffering from high blood pressure ……. posing a threat to the health of mother and baby.” I would say that the last part of the definition is the understatement of the century. If you have a preeclamptic woman who then fits she is very very unwell and requires immediate medical treatment. There is sometimes a warning of this becoming a distinct possibility. A woman who has been diagnosed with severe preeclampsia can sometimes get a bit “twitchy”. Her reflexes become very hyperactive and sometimes just the light touch of a finger on her patellar tendon will be enough to elicit a knee jerk powerful enough to kick a soccer ball the length of a football field. Sometimes though, the fit will commence with no warning at all.
A little side story…… when I was a very junior registrar in Queensland we had a woman who was being induced for severe preeclampsia and she was VERY twitchy. I was concerned that she was going to fit at any time. In this particualr job I got to go home overnight and be called in if there was a problem. There was another registrar on site in the Emergency department at the hospital overnight. I thought I should give him a heads up about the twitchy patient in case he got an emergency call to her in the middle of the night. He was VERY laid back when I told him about this patient. At the time I remember thinking – “Man, if you were telling me about this woman I’d be secretly soiling my underwear as you told me this story.” But he has like “Yeah, no problems. I’ll let you know if anything happens.” She survived the night and was induced the next day and had her baby and recovered just fine. I saw him a couple of days later and said to him I was surprised that he was so laid back. As it turned out he had emigrated from southern Africa a couple of years beforehand and had done a lot of doctoring in Namibia. As far as he was concerned he had it easy when I rang him about a preeclamptic woman. A significant percentage of the women he’d dealt with in Namibia would come to the hospital having already had their first eclamptic fit. Just goes to show - everything is relative!
Who is at risk of developing preeclampsia? The list is longish…..
first babies
pre-existing blood pressure problems
new father
male partner whose mother or previous partner had preeclampsia
limited sperm exposure
preeclampsia in a previous pregnancy
preeclampsia in your family
pre-existing kidney problems
diabetes
twins, triplets
obesity
age >40 or <18
This list is not exhaustive. There are other medical conditions which can also predispose to preeclampsia. Right now though I wouldn’t mind betting that a good number of you are going back to that list again and reading “limited sperm exposure” again and thinking what the….!!!!! Women who have less exposure to the sperm of the future fathers of their babies are much more likely to develop preeclampsia. This has been shown in numerous studies the majority of which have looked at the length of co-habitation with or without barrier contraception prior to pregnancy. This shows that part of the development of preeclampsia is dependent on factors related to the male. Note also that if the future father of your children has previously fathered children and those pregnancies involved preeclampsia you’re also at increased risk.
There is only one negative risk factor – that is, a factor which decreases your risk for developing preeclampsia – smoking. It is not recommended however that pregnant women should take up this habit in order to reduce their risk of developing preeclampsia!
Low dose aspirin is the only medication that has been shown consistently to reduce the risk of developing preeclampsia. It is not recommended for those at low risk of developing preeclampsia. However, it is recommended for use in moderate to high risk of developing preeclampsia. For example, a woman with pre-existent blood pressure issues or diabetes or kidney problems (for example) may benefit from the use of aspirin.
Some early research showed that supplementation of Vitamin C and E might help prevent the development of preeclampsia – it doesn’t. Calcium supplementation only helps prevent preeclampsia if the calcium intake is below the recommended daily intake.
So, the cause is still being figured out. The prevention strategies are limited. The outcomes are potentially catastrophic. What’s the good news? – it’s relatively easy to treat.
The only way to treat preeclampsia is to deliver the baby. Well actually, it’s to deliver the placenta but you can’t really deliver the placenta without delivering the baby as well. Sure, you can use blood pressure medication to reduce the blood pressure but it is only masking the underlying process which continues unabated. This leaves one in a predicament when someone comes to the hospital with severe preeclampsia at say 28 weeks (full term being 40 weeks). You don’t really want to just pluck out their baby at such a premature gestation without a very good reason. Normally you make an attempt to control their blood pressure and then try to get their baby a bit more developed until you “cure” their preeclampsia. Delivery at such an early gestation is not taken very lightly. The baby’s organs are very underdeveloped and usually the mother is given a dose of steroids to help mature the baby’s lungs, gut and brains before delivery is undertaken. The decision to deliver usually becomes necessary when either the blood pressure becomes uncontrollable or the mother’s organs show severe deterioration or if the baby is showing signs of stress. Once the baby (and placenta) are delivered the effects of preeclampsia start to reverse. Often there can be a deterioration of all parameters in the early phase after delivery before they all start to reverse back to normal. One of the most impressive features of the recovery is the passing of large amounts of urine indicating an offloading off all the excessive fluid/swelling that the woman has accumulated over the prior weeks. The twitchy patient that I mentioned previously had a massive diuresis (passage of urine) after she was delivered. I had not met her prior to the time of her delivery and I didn’t realise just how much fluid she had accumulated (and then peed out) until weeks after her baby was born. This woman who I had thought initially was quite overweight ended up having legs the size of toothpicks once she had lost all of her extra fluid. She looked like a different person.
A brief note on HELLP syndrome. This stands for Hemolysis (breaking down of red blood cells) Elevated Liver enzymes (abnormal liver function) Low Platelets (low clotting cells). It probably represents a variant of severe preeclampsia but this is controversial. Up to 20% of women with HELLP syndrome do NOT have high blood pressure of proteinuria It is unclear what causes HELLP syndrome. What is clear that these women almost always need delivery within 48 hours as these patients can deteriorate suddenly and severely with potentially catastrophic outcomes for mothers and babies.
Everyone woman’s journey through the disease of preeclampsia is different. One woman might have her kidney function affected the most. One woman might have the most problems with her high blood pressure. All of them are different. I remember one of my senior registrars telling me when I first started on the O&G training program that he had once been told by a general physician that “preeclampsia was
far too interesting a disease for obstetricians to look after.” To this day I take that as a compliment not as a criticism.
