What is the reason for the ongoing mortality of mothers and infants due to pre-eclampsia?
After going through a regular pregnancy, Emma Bailey believed that her second childbirth would be relatively smooth. However, at 34 weeks, she started experiencing sudden stabbing pains below her ribcage.
She recalls, “The pain was unbearable.” After being taken to the hospital, she was discharged with a diagnosis of anxiety. However, she had to be readmitted the following day due to severe pain.
The discomfort she felt is a common sign of a severe type of pre-eclampsia, a pregnancy issue that results in dangerously elevated blood pressure. In uncommon situations, it can lead to a liver and blood clotting condition known as HELLP syndrome, which can be life-threatening for both mother and baby.
Instead of starting the only available treatment, which is delivering the baby as soon as possible, the consultants at Broomfield hospital in Chelmsford, Essex, appeared to be unaware of the risk she was facing.
Bailey shared that she spent a total of four days in the hospital, where she underwent tests and consulted with different doctors. She was also provided with strong pain medication for her rib pain, which remained unexplained. However, by the time the doctors took action, her liver had already ruptured and she was experiencing severe bleeding. Despite their efforts to perform an emergency caesarean, unfortunately, it was not enough to save her daughter.
Mia, who was identified by name, passed away after two days. Bailey was put into a medically induced coma and spent several weeks in the intensive care unit while her liver recovered.
“I managed to survive, but it was a close call,” she states. “It’s difficult to discuss, but I believe it’s important to bring attention to prevent this from happening to other women.”
Although pre-eclampsia impacts around 6% of pregnancies and results in roughly 500,000 fetal deaths and 70,000 maternal deaths annually worldwide, especially in low- and middle-income countries, our knowledge of the causes and treatment of pre-eclampsia is still limited.
Although regular blood pressure checks during pregnancy have helped decrease the number of maternal deaths from pre-eclampsia in the UK, they still occur. The most recent MBRRACE (Mothers and Babies: Reducing Risk Through Audit and Confidential Enquiries) report for 2019-21, created by Oxford University’s national perinatal epidemiology unit, shows that there has been a 15% increase in the number of women dying during childbirth or within six weeks after pregnancy in the UK over the past decade. The report covers a period of three years and reveals that nine women died from pre-eclampsia, all of which could have been prevented.
According to Ian Wilkinson, a clinical pharmacologist and professor at Cambridge University, the two primary factors resulting in death from pre-eclampsia are stroke and prolonged seizures. In pre-eclampsia, there is an increase in blood pressure and leakage in the capillaries, which can cause bleeding in the brain and lead to a stroke. Alternatively, the brain can become inflamed, causing seizures. Unfortunately, in cases where women have died from pre-eclampsia, it is often due to a lack of awareness about symptoms such as severe headaches being indicative of an emergency, or inadequate monitoring by caregivers.
However, fatalities caused by pre-eclampsia only represent a small portion of the larger impact it has. Pregnant women who suffer from this condition are at a significantly higher risk (20 times greater) of developing chronic hypertension compared to those who have no pregnancy complications. This also puts them at a two to three times greater risk of experiencing a stroke or heart attack in the future.
Pre-eclampsia also appears to affect the biology of the developing baby such that those children are more likely to be born with congenital heart disease and kidney disorders and are at a greater risk of experiencing problems with blood pressure and related cardiovascular conditions throughout their lives.
However, researchers are optimistic that further research will provide valuable information to enhance our capability to detect women who are at the highest risk and direct treatments specifically towards them.
Lack of awareness
The National Institute for Health and Care Excellence suggests that pregnant women who are at a higher risk for pre-eclampsia should take a daily dose of 75-150mg of aspirin starting at 12 weeks of pregnancy until delivery.
Although it is not a complete solution, several research studies have indicated that aspirin may assist by inhibiting the creation of certain hormones believed to play a role in the progression of the ailment. Despite this, it seems that many women who could potentially benefit from aspirin therapy are not receiving it.
According to Professor Andrew Shennan, an obstetrics expert at King’s College London, pregnant women over the age of 40 are advised to take aspirin as a precaution. However, it has been found that many women are not receiving this information and therefore not taking aspirin. In a recent review of their hospital, it was discovered that only 20% of eligible women were being prescribed aspirin. This is concerning and efforts should be made to address this issue.
When it comes to evaluating the likelihood of pre-eclampsia, it is a complicated situation and Shennan believes that there is still a lack of understanding among medical professionals about who is at the highest risk. Women with pre-existing autoimmune conditions or diabetes, a body mass index over 35, a history of previous pregnancy complications, a family history of pre-eclampsia, and those carrying multiple babies are all more prone to the condition. Studies on the population in the UK have also revealed that pre-eclampsia disproportionately affects black women and those of Asian descent.
Due to the potential connection between pre-eclampsia and inadequate blood vessel development in the placenta, the NHS now offers a new blood test called placental growth factor testing. This method is believed to be a dependable means of identifying pregnant women with the condition, but some professionals suggest earlier intervention may be necessary.
Wilkinson and Jenner, from Addenbrooke’s hospital in Cambridge, are enlisting first-time mothers-to-be for the Poppy study. This clinical trial, funded by Wellcome, will track the women’s cardiometabolic health from preconception to post-partum through various tests to evaluate their heart and blood vessel health.
The goal is to discover new information that can help identify women who are at risk for pre-eclampsia due to placental health issues and potential long-term cardiovascular risks. This will improve the ability to predict and target interventions for those at risk. Jenner expresses hope that this research will lead to a more accurate prediction method for pre-eclampsia in women.
There is a demand for efficient remedies.
Identifying women at risk for pre-eclampsia earlier may lead to progress, but the effectiveness of treatment can only improve if more therapy options are developed. Currently, doctors can only monitor the condition and potentially deliver the baby early, which is linked to many negative health consequences, aside from low-dose aspirin.
Infants who are born prematurely, even by just a few weeks, are at a higher risk for facing ongoing social and emotional challenges. Those born before 34 weeks may also face additional complications such as cerebral palsy, vision and hearing impairments, and decreased cognitive abilities. According to Shennan, the need for early delivery to address these issues is a significant concern, as premature birth has a significant impact on the body.
Following the thalidomide scandal during the 1950s and 1960s, where over 10,000 babies were born with serious defects globally, there has been a reluctance among drug developers to create new treatments specifically for pregnant women. As a result, according to Wilkinson, most clinical trials have centered on supplementing with familiar vitamins, minerals, or medications like aspirin that have a proven track record of safety.
Shireen Meher, a consultant in maternal foetal medicine at Birmingham Women’s and Children’s NHS foundation trust, is investigating the potential benefits of high-dose calcium supplementation in preventing or reducing the severity of pre-eclampsia. She cites a review of eight clinical trials, which included over 10,000 women with low-calcium diets, and found that a high dose of mineral supplementation decreased the risk of pre-eclampsia by approximately 36%. However, the reliability of this data was considered to be relatively low due to significant differences in the initial risk of pre-eclampsia among the participants, highlighting the need for more research on the topic.
Meher explains that low levels of calcium may increase blood pressure by stimulating the release of hormones such as parathyroid hormone and renin. The theory is that supplementing with calcium may decrease this hormone release and prevent the narrowing of blood vessels, ultimately reducing the risk of hypertension.
Although current data indicates that calcium supplementation may only be helpful for women with insufficient dietary calcium intake, Meher argues that there may be a higher number of women in the UK who lack this mineral than previously estimated.
The Birmingham University trial, called CaPE, is currently recruiting 7,756 pregnant women who are believed to be at a high risk for developing pre-eclampsia. The goal is to investigate if taking 2g of calcium daily during pregnancy can reduce their chances of developing the condition. A baseline survey was conducted with some of the recruited women, revealing that many of them do not have enough calcium in their diet. If successful, calcium could be a cost-effective and easily accessible solution with no known safety concerns.
According to Shennan, there is a requirement for stronger treatments to tackle certain aspects of the disease process. He suggests that the use of messenger RNA technology in Covid-19 vaccines and upcoming cancer therapies could potentially be beneficial.
“He suggests that by utilizing this method, it may be possible to inhibit specific chemicals believed to play a significant role in the development of the disease. These chemicals are indicators of placental function and there is some indication that suppressing them could potentially improve or delay the onset of sickness. While it is still in its early stages, prominent organizations such as the Gates Foundation have taken interest in this treatment, which involves administering an infusion to address pre-eclampsia.”
Bailey’s primary wish is for increased efforts to educate the healthcare system about the severity of pre-eclampsia, especially if symptoms are not detected and monitored promptly.
Together with her spouse Grant, she took legal action against Broomfield hospital following her encounter, and they reached a settlement outside of the courtroom. In 2021, she delivered a thriving daughter named Grace.
“After Mia passed away, I had to allow my liver to fully heal. About a year and a half later, I became pregnant again,” she explains. “The following nine months were filled with anxiety, but we had a fantastic specialist at St Thomas’ Hospital who discussed various measures to prevent a recurrence. These included taking aspirin throughout the pregnancy, and thankfully, I did not experience any complications.”
“Our goal is to increase awareness of these symptoms and prevent other families from experiencing the loss of their children.”
If you are expecting your first child, you can learn more about the Poppy study by clicking here.