G5. Pre-eclampsia, a prenatal complication.

Preeclampsia/eclampsia/hypertension in pregnancy is a perinatal/reproductive condition that can significantly increase the risk of death for a pregnant or early postpartum woman and can increase the risk of prematurity and low birth weight for infants. Infant mortality may also be a risk. The condition occurs in 5-8 percent of pregnancies in the U.S. and internationally. The rate has increased 25% in the last twenty years in the U.S. and is a significant risk of mortality for women and infants. (3) 

     Preeclampsia can be life threatening for the mother and baby and may increase the infant's later risk for developing autism. Roughly, in the US preeclampsia may affect approximately four to eight percent of all pregnancies, or 4-8% of an average of 3,978,497 live births in the US per year. (cdc.gov) Simplifying slightly would give 4-8% of 4 million/year or 160,000-320,000 pregnancies each year- roughly. International averages are worse with 5-8% of pregnancies affected by preeclampsia and with a mortality rate that makes it the leading cause of pregnancy related death for women.

Symptoms:

• High blood pressure and protein in the urine are typically watched for during prenatal care, other symptoms to report to your prenatal healthcare team include sudden onset headaches, visual disturbances, and swollen painful abdomen, according to Ob/Gyn specialist Dr. Druzin. Read more: Pre-eclampsia a leading cause of pregnancy related death, (sfgate) 
• Other symptoms of preeclampsia may include an increased risk for severe nausea and vomiting (hyperemesis) and dehydration during early pregnancy or throughout the pregnancy. Excess fluid retention and difficulty clearing toxins may be symptoms that start midway or later in pregnancy. Edema may be more severe than swollen feet and ankles, swollen hands and face may suggest more severe preeclampsia.
•  Preeclampsia is a prenatal condition that may include hypertension - high blood pressure - but sometimes the life threatening risk of  seizures can occur without there having been very high blood pressure, and may even occur after delivery (rarely).  

The condition has been found to be associated with twice the risk of autism in the children of mothers who had developed preeclampsia during their pregnancies. And the association was strong, the more severe the woman’s symptoms of preeclampsia had been, the more likely her child was to have gone on to develop autism.

Risk factors may include genetics, medical and prenatal history, age, ethnicity, and socioeconomic factors may increase risk of preeclampsia due to stress or lack of access to health care or healthy foods. Nutrient deficiency or imbalance may also be risk factors. High fat diets in animal studies can cause symptoms of preeclampsia within a few weeks.(Ge, 201, ref) The balance of omega 3 fatty acids ( fatty fish, krill oil, flaxseed meal, walnuts)  and omega 6 fatty acids (vegetable oils) may be involved. Omega 3 fatty acids can have an anti-inflammatory effect while omega 6 may increase inflammation. Omega 3 fatty acids (EPA/DHA) may also help protect against seizure risk by improving vascular and nerve health and membrane ability to control transport into the cell.

High risk: 

• History of preeclampsia
• Expecting twins or more (multifetal gestation)
• Chronic Hypertension
• Type 1 or 2 Diabetes mellitus; or gestational diabetes, (p 135, 4, 5) 
• Renal disease
• Autoimmune disease (such as rheumatoid arthritis, sarcoidosis, multiple sclerosis,(3), SLE/lupus, antiphospholipid syndrome)
• Polycystic Ovarian Syndrome (3)
• In Vitro Fertilization (2, 3) (without regard to menstrual cycle, may involve lack of the corpus luteum & production of relaxin, 2)
• Sickle Cell Anemia (3) Sickle Cell disease, (60% increased risk)  with HIV, (300% increased risk) (link.1)

Moderate increased risk:

• No history of previously having given birth (first pregnancy or incomplete pregnancies)
• Obesity (BMI >30)
• Prior pregnancy resulted in an infant who was low birth weight or small for gestational age or there was some other adverse pregnancy outcome.
• Family history of preeclampsia (for example, the pregnant woman’s mother or sister/s, or aunt/s or grandmother on the maternal side of the family had preeclampsia, genetics can be involved.)
• Black/African American race
• Low income level
• Maternal age greater than 35 years old or less than 20 years old. (3) very young women, (G5.3);  very young women who are also overweight, (G5.4); maternal age over 40, (G5.2);
• More than ten years spacing between a previous pregnancy and the current pregnancy.

Low Risk:

• Previous full term delivery with no complications.

Unknown if associated with risk of preeclampsia:

• History of a stillbirth in a previous pregnancy.

Dietary Risks or Imbalances that may be associated with preeclampsia:

• Reduced omega 3 to omega 6 fatty acid ratio, (p 136, 4, 6) (vegetable oils)
• Trans fats, (p 136, 4, 7)
• Low glycine level, (p 136, 8)
• Low choline intake, (p 136, 4, 9, 10, 11, 12, 13, 14)
• Low Vitamin D
• Low Magnesium
• Very low Calcium intake, (G5.1)
• TRPA - Pre-eclampsia may involve over-activity of the TRPA1 channel, which have mechanico-sensitive properties (may open to increased intra-abdominal pressure), and may also be activated by increased acidity (cellular acidosis created by weak acids, G.??); or other TRP channels may also be involved  - more research is needed: (G.78, G.79, G.80, G.81, G.82, G.83).
• The inflammatory NF-kB pathway has been found to be as much as ten times more active in the placenta of women with preeclampsia compared to women with a normal pregnancy. (Rui 2016) Diets with more vegetables and fruits and other antioxidants may help inhibit the NF-kB activity and increase our own antioxidant production. See G10: Nrf2 Promoting Foods for menu ideas.

The prenatal nutrition book Real Food for Pregnancy: The Science and Wisdom of Optimal Prenatal Nutrition by Lily Nichols, RDN has a helpful section about preeclampsia along with tips for other common discomforts of pregnancy.

Genetic factors may be involved as it can be more common among family members and some ethnic groups. Women with Black or African American heritage are at increased risk and also individuals with Sickle Cell disease, which is more commonly found in people with Black heritage. 

    Statistics showing age & racial difference in maternal mortality, (2011-2013, see Figure 1: link) suggest that health problems in older black women may be a problem beyond racial bias or lack of healthcare access due to low economic status. A bill proposed by Senator Kamala Harris, S.3363 - Maternal CARE Act, 115th Congress (2017-2018), about the increased maternal mortality rate for black women mentions hypertension and preeclampsia as one of the risks that can be reduced with better access to health care. Stress due to racial bias may be a factor as the increased mortality rate for black women can not be explained by economic status alone, as there is increased risk independent of income and education levels. See points 7 and 8: (.congress.gov/bill)

    Black women may be more at risk for Hypertension and it may be due to change in the diet and balance of nutrients from typical African patterns to U.S. diet. which may have been lower in calcium and higher in magnesium and fiber than the average U.S. diet.

    Family genetics may be a factor in risk for preeclampsia. Women with sister/s, a mother, maternal grandmother or aunt/s who had preeclampsia are at increased risk of also having the condition. 

• Chronic illnesses including hypertension, Type 1 or 2 Diabetes or gestational diabetes, renal disease, autoimmune disease, or Polycystic Ovarian Syndrome may increase risk of preeclampsia during a pregnancy. 
• History of prenatal hypertension or preeclampsia in a previous pregnancy increases risk of having it again in later pregnancies. 

• History of prenatal hypertension or preeclampsia in a previous pregnancy may  increase risk of having it again in later pregnancies. 
• In vitro fertilization  with one or more fertilized eggs may increase risk of preeclampsia.
• Expecting more than one infant may increase risk. 
• Never having had a baby or having ten years or more in between pregnancies also may increase risk. 
• Having had a previous infant born low birth weight or small for gestational age may increase risk of preeclampsia in future pregnancies. 
• Obesity with a BMI greater than 30 may increase risk of hypertension or preeclampsia during a pregnancy. 
• Being over age 35 or under age 20 is also a risk factor.

Socio-economic factors such as being low income may increase risk of preeclampsia occurring. Minority or low income groups may have less access to prenatal care, prenatal vitamins, healthy foods, and safe places to exercise. More exposure to air pollution and increased emotional or physical stress may be factors that increase health risks for minority or low income groups. Oxidative stress is increased by emotional or physical stress and by exposure to air pollution. 

    Many chronic illnesses involve oxidative stress and renal disease decreases the ability of the body to remove toxins. Preeclampsia can lead to increased toxins within extracellular fluid and edematous swelling in the lower legs, hands and face. Eclampsia is a term used to describe the condition when it is more severe and seizures have occurred. Delivery of the infant and placenta may be necessary if the seizures can not be stopped (magnesium sulfate is given intravenously,it can help reduce overactive nerve signals and muscle cramps). Dysfunction in the placenta seems to be involved in the underlying cause of preeclampsia. 

     Preeclampsia generally resolves within 48 hours after delivery. It is rare but occasionally seizure symptoms can start postpartum and still be life threatening for the mother but she would have been released from the hospital already.

At the systems level of healthcare research and provision of health care, women of minority groups may not receive care that is individualized for their body type. Anatomical differences in pelvic bone shape (narrower) may increase the risk of delivery complications for petite or young women of Black or African American heritage (Women's Birth Canals; Size and Shape) and may increase the risk of preeclampsia due to increased intraperitoneal pressure (less space for the fetus, more pressure on TRP channels which may not be functioning normally). 

    Research regarding treatment effectiveness that didn’t include minority groups as participants might not be as effective or as safe for all ethnic groups or body types as the results suggest. 

    A position recommended to help reduce risk of breech delivery  (G.glowm)  may also be helpful for reducing symptoms or risk of pre-eclampsia by reducing the intraperitoneal pressure. The Knee-Chest Position elevates the hips above the shoulders which would help reduce internal pressure. See the next section with prenatal resources.

TRP channels are formed by the body from a special type of protein which can group together and form clusters that act as tunnel shaped bridges or valves that cross membrane walls. The TRP channels are found throughout the body in cells and organs and anywhere else a membrane is found. They are essential and survival would be difficult without them so medications that simply block their activity may be dangerous. Some success has been found with reducing the activity when overactive TRP channels are part of a disease process. Whenever a condition has problems with fluid collecting in the form of swollen ankles or fluid collecting around internal organs there may be a problem with overactive TRP channels. 

     As a valve the TRP channels are designed to leak if pressure builds up to great within an organ or cell. Picture a balloon being blown up, expanding fuller and fuller, and eventually you have to stop or the balloon will pop. The TRP channels would activate at a certain point of "stretch" or pressure on the membrane wall and fluid or air would leak out of the overstretched cell or organ. The lungs can have difficulty moving air when there are TRP channel problems and the heart or intestines or abdomen can have difficulty with fluid collecting instead of being transported out for detoxification by the kidneys.

     In the prenatal condition pre-eclampsia the physical size of room available for the growing baby may be part of the problem. The abdomen of smaller women and women with a smaller pelvis may simply be too snug a fit for growing baby - especially if there are also some diet imbalances that promote fluid retention (swelling). Women in the past were encouraged to avoid salt on the theory that too much salt and sodium may cause swelling for some people with some conditions. Other conditions actually require a little additional sodium and pregnancy can be one of those. Restricting sodium can make pre-eclampsia worse. A medical hypothesis suggests women try changing their position instead and physically relieve the internal pressure on the abdomen by getting in a position that places the head lower than the abdomen. 

     Kneeling with head on a pillow on the floor or on a bed is one position that has been found helpful to relieve pressure on the pregnant abdomen and has been proposed as a preventative treatment for women with pre-eclampsia to help prevent the condition from worsening. Relieve pressure and there is less leaking from the TRP  channels and less fluid collecting to add even more pressure. The Medical Hypothesis mentions the Knee-Chest Position  (G.82), but does not include the TRP channel details that I've added here.

      The position has been used in prenatal health care for helping women with umbilical cord prolapse and to help reduce the risk of having a baby in the breech position. A breech or head up position for the baby is more of risk for natural childbirth and a C-section might be recommended if the baby is in a breech, head up position, because then the baby would be born feet first which can be more dangerous than the typical head first deliver.  See the linked article about cord prolapse for a drawing of a pregnant woman in the Knee-Chest Position, from Myles Textbook for Midwives, 11th edn. (1978). The baby can be seen in the cross section anatomical drawing, insets of a baby in the breech position and more typical head-down position are included in the image. (G.83)

     As a preventative therapy the woman is recommended to spend time each day relaxing in the Knee-chest position for twenty to thirty minutes at least each day during the last few months of pregnancy when the baby is taking up more space. The position looks awkward but with a pillow and book to read or TV to watch it can be comfortable for the over-sized abdomen. I spent time in the position after doing a few other stretches or yoga positions that are recommended for strengthening the muscles involved in a natural delivery. (G.blissbirthyoga) (G.jamiehansonyoga)

     The use of the Knee-chest position for a prolonged delivery and safety precautions are discussed in an article for midwives. (spinningbabies) See your health care provider for further guidance on the safety of exercises and dietary guidance for pregnancy. 

• Pre-eclampsia may involve over-activity of the TRPA1 channel, it also has mechanico-sensitive properties or other TRP channels  - more research is needed: (G.78, G.79, G.80, G.81, G.82, G.83);  

 Pre-eclampsia is a frequent and life threatening problem for pregnant and postpartum women that can occur prenatally or up to 48 hours after delivery. The primary cause of the syndrome has been unrecognized in the medical field. However, the treatment and prevention of magnesium deficiency has been well understood in the dairy industry and the symptoms of the two conditions are very similar.We study animals in medical research because it is unethical to experiment on humans. Farmers and vets care for dairy animals because it is ethical and profitable to help maintain their health. What they learn can help us understand other mammals too - such as humans.Hypomagnesemia, also known as grass staggers, can occur in the pregnant or postpartum cow, but it can also occur in herds feeding on low magnesium fields. Weakness and falls occur in the cattle and they recover when feed is provided that contains adequate magnesium. The best treatment is prevention by providing extra magnesium if the feed has low levels. [1]

     Magnesium deficiency can cause leg cramps, constipation, weakness, falling, cardiac arrythmias, edema and hypertension, anemia and poor immune health, ringing in the ears, irritability and headaches, and when severe seizures are possible. [2] I have had some of these symptoms - including the "wobbles" - feeling weak in the legs and almost stumbling. These symptoms are quite similar to those described for pre-eclampsia and at its most severe seizures are also a risk.

     Current care for a human with pre-eclampsia might involve calcium channel blocker pharmaceuticals prenatally for controlling hypertension and intravenous doses of magnesium sulfate in the ER or delivery room for preventing or treating eclamptic seizures. Calcium causes muscle fibers to contract and magnesium allows them to relax.

     Calcium channel blockers are patent-able pharmaceuticals trying to perform the job nature assigned to magnesium. The movement of potassium and sodium through ion channels in nerve cell membranes is well understood. A similar interaction is known about calcium and magnesium in the contraction of muscle fibers. Magnesium is the main gate keeper inside of the cell; it can prevent entry of calcium. When low on magnesium the muscles may be flooded with calcium and the constant contraction of the muscle fibers can turn into early labor cramps and possibly seizures.

     Puffy ankles (edema) means intracellular fluid is leaking out and more calcium channel blockers are necessary, but more magnesium please. The prenatal woman is low in magnesium because she has been using extra to grow a baby - she can't grow a baby out of pharmaceuticals.

     Eight percent of pregnancies may be affected by pre-eclampsia/eclampsia and the current medical recommendation suggests that calcium and aspirin might help. [4] A different source states that the condition is a problem for up to 10% of women in developing nations and affects between 3-5% of pregnancies for women in the USA. [9]  Pregnant people are already told to consume extra calcium in their diets. If that strategy were working then why do eight percent of pregnancies still have pre-eclampsia problems?

     Magnesium supplements have been reported to be helpful for preventing leg cramps during pregnancy in one study but results from another study didn’t replicate the results. [5]  A large study has begun based in Brazil that plans to provide the trial group of prenatal participants with two 150 mg magnesium supplements per day throughout the pregnancy in the hopes of preventing pre-eclampsia and reducing the number of infants born prematurely or at a low birth weight. [10] Another study focused on assessing the difference in long term mineral status of patients who had pre-eclampsia prenatally compared to those who didn't. The results found that long term calcium status was the same which does not support the current theory that calcium deficiency is involved in the condition. [11]

     A different study focused on the difference in current trace mineral status between patients with pre-eclampsia and those without. Blood levels of copper, zinc, selenium, calcium and magnesium were measured. Copper was the only mineral found to have similar levels between the two groups. The blood level of the other four minerals was significantly lower in women who had pre-eclampsia than in the group without the condition during their pregnancy. [12]

     When the body is too low in magnesium then the body will increase hormone levels that cause a drop in calcium levels. Too much calcium and too little magnesium in the blood can cause heart symptoms so there are several ways the body can prevent an imbalance between blood levels of calcium and magnesium. A study that looked at whether magnesium sensitive genes were involved in blood pressure control during pregnancy did find that one was more active in pregnancy compared the non-pregnant group.  The gene TRPM6 was more active in the pregnant group than in women in the control group. [13]

     Other research regarding the condition has noted an increased risk among close family members (mothers, daughters, sisters - if one has pre-eclampsia, other close female relatives are statistically more likely to also experience it in their pregnancies.)

     A study that measured the vitamin D, hormone D, parathyroid hormone, albumin, and calcium blood levels of postpartum women who had had pre-eclampsia and those who hadn't during their pregnancies and found no significant difference in any of the levels between the two groups. Both groups had low vitamin D levels but normal levels of hormone D, parathyroid hormone, albumin and calcium. [15]

     A study at the University of Benin found a significant correlation between low magnesium and increased prevalence of pre-eclampsia. The study concludes with a clear recommendation that consuming magnesium rich foods during pregnancy may improve the outcome:

"Pre-eclampsia and pre-term birth are associated with hypomagnesemia in pregnancy; hence, magnesium supplementation or magnesium-rich diet consisting of green leafy vegetables, soy milk and legumes may improve outcome." [14]

A review of research regarding magnesium and prenatal health also concluded with a recommendation for pregnant women to consume adequate magnesium rich foods:

"This review provides recommendations for further study and improved testing using measurement of red cell magnesium. Pregnant women should be counseled to increase their intake of magnesium-rich foods such as nuts, seeds, beans, and leafy greens and/or to supplement with magnesium at a safe level." [16]

Magnesium sulfate is used during labor and delivery to help prevent seizures in women with pre-eclampsia/eclampsia. I was told that the large dose feels painfully like fire in the veins. Which makes sense because it is an electrically active ion typically found in large amounts only within cell fluid rather than also freely available within the blood plasma. 

     Some clients were very motivated to eat better if it would help prevent blood pressure problems from reoccurring and reduce the possibility of IV magnesium from being necessary. Simple solutions like pumpkin seeds and the DASH diet may be safer too. The high dose of intravenous magnesium sulfate can lead to cardiac problems and patients who receive the treatment are carefully monitored which takes additional staff time and other medical resources. [6] 

Pre-eclampsia can be prevented by eating more magnesium rich foods throughout pregnancy. Beans, nuts, seeds and dark green vegetables are rich in magnesium. Chocolate is a good source, and there is a little magnesium in most foods. Whole grains are also good sources except the phytate content reduces mineral absorption. Shelled pumpkin seed kernels are similar to sunflower seeds in texture but they are greenish in color. Both are good sources of magnesium and other nutrients. Pumpkin seeds are a good vegetarian source of zinc, an essential trace mineral.

     Mom and baby need magnesium daily. Having a moderate calcium intake will actually help both nutrients to be more usable to the body, baby, and bones. Frequent use of carbonated drinks, coffee, black tea, and acidic juices can cause the kidneys to waste magnesium. A diet high in meats and dairy products is also more acid producing during breakdown and bone stores of magnesium may be used during excretion of the waste products if enough additional magnesium isn't available from the diet. 

     Our kidneys actively save calcium while using magnesium to remove the excess acid or excess calcium. Use of calcium rich OTC drugs like Tums or Rolaids frequently may decrease magnesium absorption. The intestines may not be absorbing magnesium well. Calcium is rare in nature except in dairy products. Our bodies expect lots of magnesium and not much calcium from our day's intake. Too much vitamin D, when in the  active form, can cause even more calcium absorption in the intestines.

     Magnesium chloride or magnesium sulfate containing skin creams may reduce leg cramps and other prenatal discomforts. Magnesium sulfate, also known as Epsom salt, can provide magnesium and sulfate, both essential minerals in a foot soak or bath.  Twenty minutes soaking with about one cup of Epsom salt in a half bath of warm but not excessively hot water can be soothing and nourishing as well. Staying in too long may cause excess absorption and may lead to loose stools for a 24 hour period or even a slow heart rate ans weak muscles if you happened to fall asleep in the bath. Magnesium is so soothing it can cause the smooth muscles to relax too much.

     Herbal teas are very nourishing in general - a few would not be recommended with pregnancy but raspberry leaf tea has been used successfully for generations.

“Raspberry leaves as well as the fruit contain many valuable vitamins needed during pregnancy. As well as containing iron, they are rich in vitamins A, C, B, E, calcium, manganese and magnesium. Magnesium particularly contributes to the strengthening of the uterine muscles.” [18]

The DASH diet was designed for helping prevent or manage high blood pressure rather than for pregnancy but pre-eclampsia can involve high blood pressure and the diet includes more emphasis on magnesium rich foods than the standard diet plans. The DASH diet plan includes a group for beans/nuts/seeds which are all good sources of magnesium. [8]

     A prenatal diet plan is primarily different from a standard woman's diet plan by having one additional dairy serving for extra calcium and the equivalent of one additional mixed snack during the second and third trimesters. During the first trimester calorie needs are similar to standard. Make the additional mixed snack a magnesium rich snack and pre-eclampsia might not become a problem. Corn chips and bean dip, peanut butter toast, or pumpkin seed kernels in a trail mix would all be snacks containing magnesium and other nutrients.

     Continuing a diet with more magnesium, zinc, selenium, and adequate calcium intake may also help protect women with a history of pre-eclampsia from experiencing heart disease symptoms later in life. An association has been observed in medical research between a history of having had pre-eclampsia and increased risk of heart disease. [17] 

     The DASH diet was designed to help reduce cardiovascular risks associated with high blood pressure. Continuing to follow the diet plan may help protect against heart disease.Differences in the TRPM6 gene may underlie both the risk for pre-eclampsia and for heart disease risk. In an animal based study providing adequate magnesium helped protect the animals with differences in the TRPM6 gene. [19] 

     TRPM6 channels are more prevalent in epithelial cells (type of cell that forms the skin and the lining of the GI tract) while TRPM7 channels are common throughout the body. Both types transport magnesium. Evidence suggests the TRPM7 type are involved in hypertension. [20] TRPM7 channels may be more involved in risk of heart attack (myocardial ischemia). [21] 

     Oxidative stress occurring prenatally has been shown to be involved in pre-eclampsia and it causes an increase in calcium flow in the placenta. [28] Magnesium deficiency in combination with elevated calcium levels may be involved in increasing oxidative stress: Magnesium deficiency and oxidative stress: an update, 2016,  [29]

     The inflammatory system seems to be connected to both pain receptors and other nerve receptors so inflammation, (which leads to oxidative stress) activates pain receptors (nociceptors) - so fibromyalgia and other inflammatory conditions cause pain receptors to be over-active due to inflammation itself, read more: Neurogenic Inflammation – The Peripheral Nervous System’s Role in Host Defense and Immunopathology [30]

     The inflammatory process causes oxidative stress: Chronic inflammation and oxidative stress as a major cause of age-related diseases and cancer. [31] 

     Adequate oxygen intake and flow to all the cells throughout the body is also necessary to prevent oxidative stress. Obesity can make it more difficult for oxygenated blood to reach all cells. [32] Moderate exercise and deep breathing relaxation exercises may be helpful for improving oxygen intake and blood flow.  

    The hypothesis regarding intrauterine pressure and pre-eclampsia mentions that the condition is associated with cell stress and that decreased magnesium levels were noted:

"Jarosz et al. reported that in lab animals exposed to IAH of 25 mmHg, histology of the brain demonstrated evidence of ischemic neuronal cell stress and decreased magnesium levels [73]." [23]

The TRP channels act as pressure release valves so that organs leak rather than overfill. Blowing up a balloon, eventually you have to stop or it will pop, and the TRP channels allow the balloon to leak instead of popping. The channels are located throughout the body and are formed from a large protein or group of proteins that cross the cell membranes. Magnesium is an electrically active mineral that provides the energy required to keep the channels closed and only allow transport of desired chemicals through the channel.

     Having too little magnesium available leaves the channels without energy to stay closed and prevent fluid or other chemicals from crossing through the channel. Depending on the difference in pressure fluid and chemicals might rush into the cell from the surrounding fluid (extracellular fluid) or fluid and chemicals might rush out of the cell (intracellular fluid) into the surrounding extracellular fluid. 

Ibuprofen or other non-steroidal anti-inflammatory drugs (NAISDs) may help protect the infant during pregnancy if an infection is also part of the problem underlying pre-eclampsia. The ibuprofen helps reduce an increase in cytokines. The cytokine flood is an inflammatory reaction that may be associated with an increased risk to the infant for mental health problems developing later in life. [7] 

Irritable Bowel Syndrome (IBS) is an uncomfortable digestive problem that is not well understood, easy to diagnose or treat, and it can be life threatening when more severe symptoms continue long term. The condition can continue for years or be a lifelong issue that may flair up at times and be less severe at other times. Read more: Treatment for IBS proves difficult survey reveals. (news-medical.net)

     The condition is common among women of child bearing age and has been associated with increased risk of prenatal complications including ectopic pregnancy and miscarriage. Preeclampsia and having a stillborn were also associated with Irritable Bowel Syndrome and pregnancy but at a lower rate than statistical significance. Increased cytokines may be involved in both IBS and preeclampsia. Read more: IBS Associated with Higher Risk for Pregnancy Complications, (MedScape)  (Khashan, 2012, ref)

Dietary Tips for IBS suggest overactive TRP channels are involved in symptom flair-up.

Dietary tips for reducing symptomscan be helpful but why some foods seem to trigger symptoms while others don't has not been well understood either. The common factor underlying why some foods seem to be triggers for many people with IBS may be the TRP channels that are found in cells throughout the intestines and actually in cells of most species in the animal and plant kingdoms.

     So what do osmo-mechanical stress, changes of temperature, chili powder, curry powder, ginger, Benicar, hormone D, steroids, and cannabinoids all have in common? They all may be able to overstimulate Transient Receptor Potential channels (TRP channels) within the gastrointestinal system and cause severe diarrhea in susceptible individuals.

• "In many cases, the activation mechanism of TRP channels is unclear (Figure 1), but known activators include specific agonists such as mustard oil (TRPA1) and capsaicin (TRPV1), an increase in intracellular Ca2+ (TRPM4, 5), temperature (heat: TRPV1, 2, 3, 4, TRPM4, 5; cold: TRPM8, TRPA1), mechanical or osmotic stress (TRPV4, TRPCs?) and phospholipase C (PLC) activation. TRP channel activity can be further modulated by intracellular phosphatidylinositol phosphates, such as PI(4,5)P2 and membrane potential, but also by inflammatory mediators, cannabinoids and steroids (Nilius, 2007; Rohacs, 2007; Nilius and Voets, 2008)." [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3012403/]

The TRP channels are a large group found in many species of life from yeast, to worms, fish and mammals. The agonists/activating chemicals for many of the types of TRP channels have not all been identified as of yet.

• [http://molpharm.aspetjournals.org/content/75/6/1262.full]

One type of TRP channels were formerly called Vanilloid Receptors, and are now called TRPV channels. Vanilloid Receptors were known to be activated by capsaicin found in hot peppers and chili powder. And more recent or less well known research has also found that they can be activated by cannabinoids and steroids, (see the link from the excerpt above), and osmomechanical stress.

     Osmo-mechanical stress might be a precursor to edema, excess fluid in the extracellular space; if an organ or cell over fills with fluid it would mechanically be adding physical pressure to the organ or cell -- and instead of popping like an overfull water balloon the TRP channels open in response to the physical pressure and let the excess fluid leak out into the extracellular space or into the area surrounding the heart for example. [http://www.ncbi.nlm.nih.gov/books/NBK92821/] 

     Fibrotic heart disease would be adding mechanical stretching stress within the heart. TRP channels are being studied for possible use in preventing fibrotic heart disease. From that research article, we are told that changes in temperature may also activate them:

"The activation mechanisms of TRP channel are highly diversified. Some TRP channels appear to be constitutively active, whereas others are activated by Gq-linked receptor activation, oxidative stress, changes of temperature, or an elevation of intracellular Ca2+ [126–128]. All the TRP channels appear to be regulated by PIP2 [134–137] ." [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3874073/]

• PIP2 = phosphoinositides = phosphatidylinositol phosphates (PIPs) = phosphorylated deriviatives of phosphatidylinositol (PI) [http://www.annualreviews.org/doi/abs/10.1146/annurev.cellbio.21.021704.102317]
• PIP2 = phosphatidylinositol-4,5-bisphosphate and PI, and phospholipase C (PLC) from the first excerpt, are involved in cannabinoid metabolism within plasma membranes: [page 9 Kendall et. al., Behavioral Neurobiology of the Endocannabinoid System (Springer, 2009, New York)]

Steroids and hormone D function similarly. And Benicar and curcumin can function similarly to hormone D. And curcumin is a medically active extract from turmeric, a powdered spice that is a main ingredient in curry powder. Turmeric is made from the root of a plant that is biologically very similar to ginger,  which is also a root that is used as a dried spice or  may be used as a chopped vegetable in stir-fry dishes and other foods. Ginger has over 400 active phytochemicals, and one of them might be acting similarly to the curcumin -- but that is speculation based on the similarity of symptoms of Irritable Bowel Syndrome that both ginger and curry powder stimulate.

     Because -- what else do osmomechanical stress, changes of temperature, chili powder, curry powder, ginger, Benicar, hormone D, steroids, and cannabinoids all have in common? -- They all may irritate Irritable Bowel Syndrome, (IBS), for some people, along with emotional stress and other things like eating fructose in much quantity (example: from a piece of fruit or fruit juice) or gassy vegetables like cabbage and cruciferous vegetables and beans (gas would be adding mechanical pressure to those TRP channels which might be an over-active culprit in IBS patients).

• The book, "Tell Me What to Eat If I Have Irritable Bowel Syndrome; Nutrition You Can Live With; Including Dozens of Healthful Mouth-Watering Recipes," by Elaine Mager, M.P.H., R.D., includes dietary advice and other information about Irritable Bowel Syndrome (IBS). (Warning - most of the recipes contain gluten and if there is an underlying gluten sensitivity causing oxidative stress it may increase risk for pr-eclampsia;  a Celiac Sprue forum [33] that included questions and comments about whether anyone else with celiac gluten intolerance had also experienced pre-eclampsia or HELLP complications of pregnancy and if so any ideas why they might co-occur. HELLP is a blood coagulation problem which I didn't look into but Celiac sprue and pre-eclampsia may be likely to co-occur because both involve oxidative stress.
• Re corticosteroids and hormone D:  http://www.oapublishinglondon.com/article/1471

• Disclaimer: Opinions are my own and the information is provided for educational purposes within the guidelines of fair use. While I am a Registered Dietitian this information is not intended to provide individual health guidance. Please see a health professional for individual health care purposes.
• The Academy of Nutrition and Dietetics has a service for locating a nutrition counselor near you at the website eatright.org: (eatright.org/find-an-expert)