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Pre-eclampsia associated with earlier onset of cardiovascular risk factors

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Women who have experienced pre-eclampsia have accelerated accumulation of cardiovascular (CV) risk factors compared with women who had pregnancies without pre-eclampsia according to new research.

Pre-eclampsia typically affects 2 to 5 per cent of pregnant women and is broadly defined as the development of hypertension and high protein levels in the urine of a woman with previously normal blood pressure. In addition to the short-term risk to foetal and maternal health, pre-eclampsia is associated with an approximately doubled risk of CVD and stroke.

“Despite the known long-term risks after pre-eclampsia, guidelines do not include specific recommendations on the necessity, timing and frequency of systematic CV assessment, which is likely due to a lack of empirical data,” said study author Emma Janssen from the Maastricht University Medical Centre, Netherlands.

“As part of the Queen of Hearts study, we aimed to investigate the long-term prevalence of CV risk factors in women who experienced pre-eclampsia compared with normotensive pregnancies with no increased blood pressure to help guide proactive assessment, which in turn, may lead to more timely implementation of preventive strategies.”

 

 

In this retrospective cohort study conducted in Netherlands, data were collected from adult women with a history of pre-eclampsia (within a postpartum interval of 0.5 to 30 years) and from healthy women with a history of uncomplicated normotensive pregnancies.

Cross-sectional postpartum assessment included medical history and physical examination, 30-minute blood pressure measurements, blood and 24-hour urine sampling, vascular function evaluation, electrocardiography and echocardiography.

A total of 1,040 women after pre-eclampsia and 518 women after normotensive pregnancies were included. The researchers found higher rates of hypertension, diabetes mellitus and hypercholesterolaemia, either individually or combined, after pre-eclampsia than after normotensive pregnancies.

These risk factors occurred, on average, eight years earlier in the pre-eclampsia group compared with the normotensive group. In addition, the prevalence of hypertension increased more steeply with ageing after pre-eclampsia than after normotensive pregnancies.

In women after pre-eclampsia from the age of 35 years onwards, hypertension reached the CVD risk cut-off that is deemed sufficiently high to warrant systematic CVD risk assessment.

Janssen said: “In women who have experienced pre-eclampsia, CV risk factors occur almost a decade early, predominantly, but not exclusively, due to the premature and accelerated development of hypertension.

“Systematic CV risk assessment is warranted from 35 years of age and should be repeated regularly, at least every 5 years, to enable these women to receive appropriate preventive measures to reduce their high risk of CVD and potential sequelae.”

Dr. Chahinda Ghossein-Doha from the Erasmus University Medical Centre, Rotterdam, Netherlands, principal investigator of the Queen of Hearts study, said: “After their pre-eclampsia is managed, these women often fall through the net, without being referred for specialised follow-up.

“We need to be monitoring these young women regularly to detect any increase in risk factors in a period of their life when such an accumulation may be unexpected. For women after pre-eclampsia, taking steps to lead a heart-healthy lifestyle is important, as is discussing formal CV risk assessments with a healthcare professional.”

Pregnancy

Chemicals in plastics may be linked to high blood pressure during pregnancy

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Phthalates found in plastics and personal care products may be linked to higher blood pressure during pregnancy, a study suggests.

Hypertensive disorders of pregnancy, including pre-eclampsia, are a leading cause of maternal mortality in the US.

Higher blood pressure during pregnancy has also been linked to adverse health outcomes for both mothers and children.

While family history and lifestyle are known risk factors, growing evidence suggests exposure to phthalates may also contribute to raised blood pressure during pregnancy.

Phthalates are chemicals found in plastics, personal care products and hundreds of other consumer goods. Some can interfere with the body’s natural hormones.

Kimberly Parra, of Harvard T.H. Chan School of Public Health, said: “Our study suggests that having higher concentrations of personal care products-associated chemicals, known as phthalates, in the body might contribute to elevated blood pressure in pregnancy.

“While our study does not show that phthalates cause high blood pressure during pregnancy, it suggests that reducing exposure to this class of chemicals by limiting personal care products containing these ingredients, particularly those with fragrance, may be a way to address high blood pressure in pregnancy and improve pregnancy health.”

Researchers measured phthalate exposure and blood pressure in 338 pregnant women from the Environmental Reproductive and Glucose Outcomes Study at three points during pregnancy.

They analysed whether higher levels of the chemicals, individually and in combination, were linked to higher blood pressure or an increased risk of pregnancy-related high blood pressure disorders.

Women with higher urine concentrations of phthalates associated with fragrances and personal care products had higher systolic and diastolic blood pressure, markers of increased risk of hypertensive disorders of pregnancy.

Systolic blood pressure is the pressure in the arteries when the heart beats, while diastolic pressure measures it between beats.

Around 13 per cent of participants developed a pregnancy-related high blood pressure disorder.

Women with higher levels of certain phthalates, particularly those found in personal care products, tended to have higher blood pressure later in pregnancy.

Parra said: “More research is needed to better understand these findings, particularly whether the effects are driven by changes in oestrogen-related pathways. Additional studies should also examine the potential role of other phthalates and their replacement chemicals.”

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Higher doses of common fertility drug may increase pregnancy risks

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Higher cumulative doses of common fertility drug clomiphene citrate may increase pregnancy loss risks, according to new research.

Around one in six people experience infertility, with irregular or absent ovulation among the most common causes.

Clomiphene citrate has long been a mainstay of fertility treatment, but Adelaide University research has raised concerns about higher cumulative doses.

The new study found that high doses of clomiphene citrate accumulated over multiple fertility treatment cycles could increase the risk of pregnancy loss.

Lead author associate professor Sheree Boulet said the findings showed a clear dose-response relationship, meaning the risks increased as cumulative exposure rose.

She said: “Women who received higher cumulative doses of clomiphene citrate experienced progressively greater risks of adverse pregnancy outcomes.

“We examined more than 21,000 embryo transfer cycles across four cumulative dose categories and found that increasing the dose did not significantly improve the chance of a live birth.

“Our findings suggest there may be a point where increasing the dose offers little additional benefit while exposing women to greater risk, highlighting the importance of carefully balancing effectiveness with safety when making treatment decisions.”

Supported by the NHMRC and conducted in partnership with Boston University and the Centers for Disease Control and Prevention, researchers analysed 21,004 IVF embryo transfer cycles in the US.

Women receiving cumulative doses of 500mg to 749mg of clomiphene citrate had a 12 per cent higher risk of miscarriage, while those receiving 750mg to 999mg had a 38 per cent higher risk.

Women receiving cumulative doses of 750mg or more were also more than twice as likely to have twins or other multiple births.

Rates of spontaneous abortion, another term for miscarriage, increased as the dose rose.

Researchers also recorded more than a threefold increase in stillbirth at the highest dose, although the finding was not statistically significant because that dose was rare. Larger studies are needed to confirm the association.

The finding is consistent with an earlier Adelaide University study that showed a doubling of neonatal death in pregnancies involving clomiphene citrate. Neonatal death means the death of a baby shortly after birth.

Higher cumulative doses did not improve the chance of a live birth, but did increase twinning, which raises the risk of adverse outcomes for both mother and child.

Clomiphene citrate is one of the world’s most widely prescribed fertility drugs. It has been prescribed to millions of women worldwide since 1967 and remains a recommended first-line treatment for ovulation induction.

The drug is recognised as an essential medicine by the World Health Organization. It works by stimulating the ovaries to release eggs, increasing the chance of pregnancy.

Women who do not respond to lower doses, or who require multiple treatment cycles, may receive progressively higher cumulative doses over time.

The findings build on a series of studies from Adelaide University’s Robinson Research Institute linking clomiphene citrate with increased risks of pregnancy loss, stillbirth, perinatal death and some birth defects.

Experimental studies in mice supported these findings, showing that higher doses reduced successful pregnancies and were associated with pregnancy loss, impaired fetal growth and developmental abnormalities.

Professor Michael Davies, senior researcher and co-author of all the studies, said the latest work builds on more than two decades of Adelaide-led research into the safety of fertility treatments.

He said: “Clomiphene citrate has been used by many women since 1967, but it has never been comprehensively evaluated in large prospective clinical trials.

“Our studies indicate that women respond differently to clomiphene citrate and that increasing cumulative doses may increase the risk of adverse pregnancy outcomes without improving the likelihood of a live birth.

“The findings confirm and extend our previous studies in both human and mouse models which highlight the need to better understand the dose-response relationship and whether more personalised dosing strategies could improve safety.

“Until we can better understand these differences, it remains important that clinicians rigorously follow manufacturer’s safety recommendations and avoid unnecessarily increasing cumulative doses.

“The same questions are now being asked of newer ovulation-inducing medications, so any move away from clomiphene citrate should also be guided by robust evidence rather than assumptions about safety.”

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Women should not be pressured into an ‘ideal birth’, says health secretary

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Women should not feel pressured into an “ideal birth”, health secretary Yvette Cooper has said as she promised major maternity reform.

Cooper has returned to the Department of Health and Social Care 27 years after serving as public health minister under Tony Blair.

She said maternity and child health would be a major focus of her new role, alongside significant reforms to social care.

In an interview with the Guardian, Cooper said the changes should address any pressure on women to pursue a particular birth experience.

Families affected by maternity failures have repeatedly raised concerns that some units were reluctant to escalate medical interventions because of a preference for more natural births.

Cooper said: “I would worry about any mum feeling pressurised that there is somehow a kind of an ideal birth experience to live up to when it’s always different in every case, and you have to follow the evidence, you have to have informed choice.”

As one of her first actions as health secretary, Cooper said she intended to reintroduce binding national maternity standards.

The standards were dismantled during early Conservative NHS reforms and replaced with fragmented arrangements managed separately by individual hospital trusts.

A new maternity taskforce will draft the standards, which will have five central aims.

These include ending regional differences in levels of care and tackling racial inequalities linked to poorer outcomes in deprived areas, particularly for Black and Asian women.

Patient experiences will also form part of how standards are measured, while new targets will aim to identify underperformance before a major scandal develops.

Cooper, who became the first minister to take maternity leave while serving as a junior health minister in the early 2000s, said reports into maternity scandals had been “traumatic” to read and showed that systemic change was needed.

She said: “We’ve always said the NHS is about the cradle to the grave. I want to make it a personal crusade to put the cradle back at the heart of the NHS, and to have much more focus around maternity and child health, the very beginning of a family’s life, making that much more central to the priorities of the NHS, giving it the priority that it really deserves.”

Cooper said discussions about how maternity services could better listen to mothers’ needs had been taking place for the past two decades.

However, she said the emphasis on placing women and families at the centre of care appeared to have been lost.

She said: “It feels incomprehensible that we could be in this situation in the 2020s. I went back to look at some of the things that we’d done 25 years ago.

“And what did strike me was how much we were talking then about women and families being at the centre of care and about listening to women’s views.

“It is really shocking and distressing feeling that has somehow been lost in some of the maternity units where actually it should be the central issue.

“I had a direct interest. I was pregnant at the time. But I am really struck by it now, just feeling like there is this big gap in the priorities that the NHS has been focused on.”

Cooper said she was determined to provide a robust response to Donna Ockenden’s investigations into maternity failures at Shrewsbury and Telford and Nottingham, alongside Baroness Valerie Amos’s national investigation into England’s maternity system.

The investigations highlighted systemic clinical errors, understaffing and toxic institutional cultures. They found that hundreds of infant and maternal deaths were directly linked to failures to listen to mothers and defensive attempts to protect institutions.

Amos’s review faced criticism, including the resignation of an expert adviser over the lack of explicit warnings about “normal birth ideology”.

Families also questioned whether the review’s proposed statutory maternity commissioner would have sufficient independence.

Cooper said she remained committed to introducing the role.

She said: “In the end, the most important people in the maternity services are the mothers, babies, the families. But the point of having a maternity commissioner is to make sure that those issues are championed as part of an NHS.”

She also said reforms needed to address an oppositional culture between doctors and midwives in some trusts over when medical intervention during birth may be necessary.

Cooper said: “The thing that struck me most was the sense of women feeling they weren’t being listened to … And I think that probably does go back to issues around culture.”

Cooper, who served as foreign secretary until recently, said she was prepared for a difficult period in the health role as she sought to implement Andy Burnham’s social care reforms.

She said she remained committed to establishing the national care service announced by the prime minister the previous week.

A longstanding ally of former prime minister Keir Starmer and a former rival of Burnham in the 2015 Labour leadership contest, Cooper said she believed the change of prime minister had been necessary.

She said: “Of course it’s not easy. I really did not think it was possible to win the election when I came back into the shadow cabinet in 2022. It’s only because of what Keir did that we managed to win.

“But we had very difficult local election results … we have to respond to that. But I think we’ve got a sense of energy now.

“All of the things that Andy wants to focus on and drive are also just very much the things that that people are concerned about across the country.”

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