Category: Obstetrics & Gynaecology

Scientists Test A Potential New Therapy for Preeclampsia

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Researchers have proposed a new therapy for preeclampsia that corrects the defects identified in placental cells, and restores placental and foetal weight, which they report in the journal Redox Biology. The treatment, tested in two rodent models, successfully lowers blood pressure in the mother and resolves the characteristic preeclampsia symptoms of proteinuria and cardiovascular abnormalities.

Preeclampsia is a placental dysfunction that affects approximately 2 to 8% of pregnant women worldwide. It can have potentially complications for mother and child, and longer-term consequences for the mother. Preeclampsia symptoms are primarily arterial hypertension, proteinuria, abnormal coagulation in the placenta, cardiovascular abnormalities in the mother and foetal growth restriction. Treatments for preeclampsia are limited and mostly involve aspirin as a preventative measure, reducing the procoagulant state in the placenta and partly relieving pressure on the vascular network.

Preeclampsia is characterised by a defective placenta caused by trophoblast dysfunction. Trophoblasts are placental cells that help organise and manage the vascular network which provides the essential resources for foetal growth. At the molecular level, preeclampsia is characterised by an uncontrolled increase in oxidative stress, with excessive production of various reactive species including reactive oxygen and nitrogen species. There is a genetic component: the first gene to be identified as being implicated in the genetic forms of preeclampsia was the STOX1 transcription factor, which controls the expression of thousands of genes, especially those involved in the production of nitric oxide (NO).

In a transgenic mouse model, high accumulation of STOX1 in the placenta induced a preeclampsia-like syndrome. In preeclampsia, NO, a powerful vasodilator that promotes blood flow to the placenta, is mobilised to produce potentially toxic molecules (nitrosative stress) and its levels become insufficient in the placental vascular network, affecting trophoblast function and the vascular network and destabilising other reactive species. This creates a vicious circle and causes uncontrollable oxidative/nitrosative stress with multiple complications, also affecting maternal blood vessel cells, with potentially fatal consequences.

NO is produced by a family of enzymes known as nitric oxide synthases (NOSs). Finding a way of restoring NO production in the placenta via NOSs could represent an effective new therapy to treat preeclampsia. A years-long collaboration gave rise to a potential solution. The scientists’ research was based on trophoblasts overexpressing STOX1 and on two rodent models of preeclampsia, one mimicking early-onset forms via placental overexpression of STOX1 and the other mimicking late-onset forms by partial occlusion of the lower abdominal aorta.

The research revealed a cascade of events that ultimately led the scientists to propose a new therapy. Treating trophoblasts with BH4 (tetrahydrobiopterin, a cofactor that stabilises the NOS enzyme producing NO) corrected the defects identified in these cells, restoring production of NO rather than potentially toxic molecules. More importantly, administering BH4 to the two preclinical rodent models restored placental and foetal weight. Finally, in the early-onset STOX1 preclinical model with significant arterial hypertension and proteinuria, the BH4 treatment corrected blood pressure, excess protein in urine, and cardiovascular abnormalities in the mother. The results even suggest that the treatment may be effective in addressing the long-term effects of preeclampsia on mothers (vascular abnormalities in the brain, kidneys, heart and liver).

This research is the first step towards the development of a therapy for preeclampsia. Genetic analyses of placentas treated with BH4 showed that it corrects the expression of several genes disrupted by excess STOX1 differently than the deregulation induced by aspirin in the placenta. The scientists therefore propose that a treatment combining BH4 and aspirin could be the ultimate therapeutic solution for many cases of preeclampsia. This hypothesis needs to be validated in clinical trials.

Source: Institut Pasteur

Choice of Words Matters for PCOS Patients’ Wellbeing

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The choice of words that doctors doctors use when diagnosing female patients with polycystic ovary syndrome (PCOS) can negatively impact their wellbeing and how they view their condition later on in life, according to new research published in the British Journal of General Practice.  

PCOS can result in a range of physical symptoms, such as dysmenorrhoea or amenorrhoea, and metabolic issues. University of Surrey researchers found that the use of the word ‘raised’ by practitioners when discussing test results can lead to higher levels of body dissatisfaction and dieting behaviour amongst women, whilst the use of the word ‘irregular’ can result in concerns about fertility. 

Jane Ogden, Professor of Health Psychology at the University of Surrey, said: “Diagnostic consultations may take a few minutes, yet how these minutes are managed, what words are used and how this makes a patient feel may change how they make sense of their condition and influence their wellbeing in the longer term. It is important that doctors have an awareness of the words they use and think about how they could be perceived by patients.”  

In one of the first studies of its kind, researchers investigated the impact of PCOS diagnostic consultations and whether the language used impacted the subsequent wellbeing of patients.

To assess the impact, researchers surveyed 147 females with PCOS and asked about their satisfaction with their consultation, the language used during it and their overall wellbeing.  

Researchers found that those who had felt uncomfortable with the consultation process were more likely to report poorer body esteem, reduced quality of life and greater concerns about health in later life. Over a quarter of those surveyed were dissatisfied with how doctors managed their distress and were unhappy with the lack of rapport they had with their practitioners.  

Prof Ogden added: “Words matter, as patients often replay conversations that they have had with doctors in a bid to make sense of situations. Although words such as ‘raised’ and ‘irregular’ are simple words they are vague which can cause women to worry, as they automatically think the worst, as they have not been provided with all the facts. Such anxiety at the time of diagnosis, can negatively impact how they feel about themselves as their life progresses.” 

Source: University of Surrey

C-section Delivery Linked to Later CVD Risk

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A new Australian and New Zealand Journal of Public Health study has found that Australian children who were born via caesarean section (C-section) have a greater risk of cardiovascular disease (CVD) and obesity. These findings have prompted a call to limit the increasingly popular practice.

According to a Lancet review, C-sections are already known to have a number of negative outcomes, with evidence higher rates of maternal mortality and morbidity than after vaginal birth. C-sections are further associated with an increased risk of uterine rupture, abnormal placentation, ectopic pregnancy, stillbirth, and preterm birth. Short-term risks of C-section include altered immune development, an increased likelihood of allergy, atopy, and asthma, and reduced gut microbiome diversity. Associations of C-section with greater incidence of late childhood obesity and asthma are frequently reported.

Researchers used data from the Longitudinal Study of Australian Children to analyse the health outcomes of children delivered by C-section.

“C-section births have risen across the world with a disproportionately higher rate in developed countries. In Australia, the C-section birth rate has increased from 18.5% in 1990 to 36% in 2019 and nearly half of Australian babies are projected to be caesarean born by 2045,” said study author Dr Tahmina Begum.

A relationship was discovered between C-section births and certain cardiovascular disease (CVD) risk factors in children.

“Four out of six individual CVD risk components and the composite index of the five CVD risk components showed a positive association with C-section birth. Our study also provided a direct relationship between C-section and increased overweight and obesity among children at 10–12 years of age,” said Dr Fatima.

A biologically plausible link involved the gut microbiome, she said. “There’s an altered microbial load from C-section birth as compared to vaginal birth. This altered microbial ecosystem hampers the ‘gut-brain axis’ and releases some pathogenic toxins that cause metabolic damage.”

Other possible causes included foetal stress from physiological or pharmacological induction of labour during a C-section. She said the study provides important insights into health care policy and the strategic direction towards chronic disease risk reduction.

“Growing rates of C-sections conducted for non-clinical reasons is a major public health concern that calls for a reduction in the rate of unnecessary C-sections and their associated human and economic costs,” said Dr Begum.

Source: James Cook University

Caesarean Delivery may Increase Risk of Developing Crohn’s Disease

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A population-based study analysing over one million individuals suggests that babies born via caesarean section delivery may face a higher risk of developing Crohn’s disease later in life. The findings, published in Acta Obstetricia et Gynecologica Scandinavica, add to a growing body of evidence on long-term impacts of caesarean section delivery. 

More and more people are being delivered by caesarean section, and there is interest in understanding possible long-term health consequences of this mode of delivery. One possible route is through a lack of the early exposure of the infant to colonising bacteria via a vaginal delivery. Previous studies suggest that infants delivered by CS are at increased risks of disorders involving the immune system, such as asthma and allergies, type 1 diabetes, celiac disease, obesity, immune deficiencies, and leukaemia and other malignancies affecting young people.

In this study, all full-term individuals registered in the Medical Birth Register in Sweden between 1990 and 2000 were followed until 2017. Among 1 102 468 individuals, of whom 11.6% were delivered by caesarean section and 88.4% were vaginally delivered, caesarean section was associated with a 14% higher risk of developing Crohn’s disease after adjusting for confounding factors. No associations between delivery mode and appendicitis, ulcerative colitis, cholecystitis, or diverticulosis were found.

“Our study is the largest in this field, showing new interesting associations between caesarean section and increased risk later in life for Crohn’s disease. We hypothesise that the underlying mechanism could be the gut microbiome, but further studies will have to confirm this,” said senior author Anna Löf Granström, of the Karolinska Institute.

Source: Wiley

Study Finds No Adverse Effects Denying Nitrous Oxide in Labour

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Birthing women denied nitrous oxide(N20) to relieve labour pain as a result of the COVID pandemic received opioids instead, without any adverse outcomes for mother or child, according to a new study published in the Australian and New Zealand Journal of Obstetrics and Gynaecology. Some anaesthetists have also argued for reducing N20 use as it is a greenhouse gas.

The study, conducted at Lyell McEwin Hospital in Australia, looked at the impact of withholding nitrous oxide (N20), a decision adopted by many hospitals worldwide over fears of virus transmission from the aerosol-generating procedure.

Anaesthetist Professor Bernd Froessler and colleagues compared patient notes for all 243 women birthing at Lyell McEwin over a seven week period in March/April 2020, half of whom did not have access to N20.

They found that although opioid use “significantly increased” when N20 was withheld, there was no increase in epidural use and no change in labour duration, Caesarean section rates, birthing complications or newborn alertness.

Nitrous oxide is used by more than 50% of Australian women to relieve pain in labour, followed by epidurals (40%) and opioids (12%), according to the Australian Institute of Health and Welfare.

However, N20 represents 6% of global greenhouse gas emissions, with 1% due to medical use (ie, around 0.06% of total global warming is due to medical N20). This has led to a debate in medical circles whether it should be replaced with other methods of pain relief.

Many obstetricians argue that effective pain relief in childbirth should be the priority, particularly given the low percentage of emissions, but the Australian and New Zealand College of Anaesthetists has advocated for a reduction in N20 use in a bid to improve environmental sustainability in anaesthesia.

“Obviously no-one wants to deprive labouring women of adequate and easy pain relief but given there are other analgesic options, including epidurals and opioids, perhaps these could be considered,” said Prof Froessler.

UniSA statistician and researcher Dr Lan Kelly said that the findings should reassure women that pain relief besides N20 does not compromise their health or their baby’s.

However, in a recent Sydney Morning Herald article, principal midwifery officer at the Australian College of Midwives, Kellie Wilton, said mothers should not be made to feel guilty about their pain relief choices and suggested hospitals could introduce nitrous oxide destruction systems to allow for its ongoing use.

When nitrous oxide destruction systems were introduced in Swedish hospitals, the carbon footprint from the gas was halved.

Source: University of South Australia

Increased Odds of ADHD Symptoms in Children Born Before 39 Weeks

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Among children born at term (37–41 weeks), those born before 39 weeks are more likely to experience symptoms associated with attention-deficit/hyperactivity disorder (ADHD), according to a study published in the Journal of Pediatrics.

ADHD manifests early in childhood with symptoms of hyperactivity, impulsivity or inattention, and has known links to preterm birth (less than 37 weeks gestation). The present study is one of only a handful to investigate the associations between gestational age at term and a diagnosis or symptoms of ADHD. It is the first to include reports from teachers.

“Teachers’ reports, in conjunction with maternal reports and physician evaluations, provide valuable input for the diagnosis of ADHD,” said study author Nancy Reichman, author of the study and a professor of paediatrics at Rutgers Robert Wood Johnson Medical School. “Mother-reported symptoms generally reflect behaviours in the home or in small family or social groups, while teacher-reported symptoms reflect behaviours in a structured educational setting by professionals who work with a large number of children and observe the range of behaviours that students exhibit in classrooms.”

Prof Reichman and her team set out to estimate the link between gestational age at term and 9-year-old children’s teacher-reported ADHD symptoms.

The team analysed data on about 1400 children in a birth cohort study that randomly sampled births from large US hospitals 1998 to 2000 and re-interviewed mothers over nine years as well as teachers’ evaluations using the Conners’ Teacher Rating Scale-Revised Short Form.

The researchers found that children born early-term (37-38 weeks) had significantly higher scores on the teacher rating scales than children who were full-term (39-41 weeks) for hyperactivity, ADHD and cognitive problems or inattention, but that gestational age wasn’t significantly associated with oppositional behaviour.

Specifically, the researchers found that each week of gestational age at term was associated with 6% lower hyperactivity scores and 5% lower ADHD and cognitive problems or inattention scores, and that birth at 37 to 38 weeks was associated with 23% higher hyperactivity scores and 17% higher ADHD scores when compared with birth at 39 to 41 weeks.

“The findings add to growing evidence supporting current recommendations for delaying elective deliveries to at least 39 weeks and suggest that regular screenings for ADHD symptoms are important for children born at 37 to 38 weeks,” Prof Reichman said.

Preterm infants are at greater risk for ADHD because of immature brain development, she said. “Significant growth and development in various kinds of brain cells are observed between 34 and 40 weeks of gestation,” said Reichman. “Infants born at full-term likely benefit from the additional one to two weeks of brain growth in utero compared with those born early-term.”

Source: Rutgers University

Endometriosis Hijacks Foetal Tolerance to Evade the Immune System

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In about 10% of women, endometrium-like tissues (known as lesions) also grow outside of the uterus, leading to endometriosis. Endometriosis is characterised by pain and can cause infertility, but its molecular mechanisms and drivers remain unknown. Now, a comprehensive study reveals how lesions escape immune surveillance, by taking advantage of mechanisms for the body tolerating a foetus during pregnancy.

Definitive diagnosis and clinical response still present significant challenges, with a common treatment being hormonal therapy with surgery. Unfortunately, surgery must be repeated if lesions recur, and they often do. To improve the situation, a better understanding of how and why the lesions grow, their cellular makeup, their microenvironments, and other aspects of their biology is essential.

The Jackson Laboratory’s (JAX) Elise Courtois, PhD, in partnership with UConn Health’s gynaecological surgeon Danielle Luciano, MD, recently completed an important study to develop a comprehensive cell atlas of the disease based on lesions obtained from 14 individuals who had treatment for endometriosis

The paper, published Nature Cell Biology, includes a thorough comparison of healthy endometrium tissue and ectopic (outside their normal site) lesions. The data also describes the endometriosis microenvironment and the conditions that allow the lesions to form and grow in what should be unhospitable regions.

“The study builds a robust foundation for a better understanding of endometriosis and how it grows,” said Dr Luciano.   “It’s exciting progress that we hope leads to earlier diagnosis and the ability to specifically target these abnormal cells for better treatments.”

The research team worked with tissues from individuals who had lesion removal at UConn Health for relief of symptoms. All were also receiving hormone therapy, the most frequent endometriosis management strategy. Not surprisingly, given that lesions are described as endometrial-like tissues growing in the wrong place, the cellular composition of the lesions in the peritoneum were quite similar to that of the normal endometrium. On the other hand, ovarian lesions had extensive differences in both composition and gene expression from the peritoneal ones. So while both ovary and peritoneum are receptive to the formation of lesions, they represent different environments and lead to important cellular and molecular differences between the two sites. The finding indicates that site-specific therapeutic design may be necessary to develop more effective treatments.

Another aspect of endometriosis is that, like cancer, the lesions represent abnormal growth that would typically be eliminated by immune surveillance. The researchers therefore investigated the immune cells in the peritoneal lesion microenvironment to see why they do not eliminate the abnormal lesion cells. They found that macrophages and dendritic cells contribute to conditions that promote immune inhibition and the promotion of immunosurveillance escape. Their specific characteristics are similar to those associated with foetal tolerance during pregnancy, which suggests that endometriosis hijacks a necessary, naturally occurring immune process to allow for lesion formation and persistence.

The paper details other aspects of both normal endometrium and ectopic lesions, including properties of vascularisation and the drivers of regeneration in endometrium and, perhaps, the formation of lesions in endometriosis. Of particular interest were key differences in the vascularisation of peritoneal versus ovarian lesions, further emphasising the site-specific nature of endometriosis. Also of note was the identification of a previously uncharacterised population of epithelial cells that may be progenitor cells for both endometrium and lesion formation, but more work is needed to define their precise role.

“Single cell analyses and hyperplexed antibody-based imaging techniques offer powerful insights into the complexity of the endometriosis microenvironment,” said Dr Courtois. “Understanding this complexity will be key for developing the new, efficient diagnostic and therapeutic tools that are so badly needed.”

Overall, the data captures a full description of endometrium and lesions, laying a strong foundation for understanding the vital cellular players and molecular dynamics of the disease. The data represents an important step forward for research into endometriosis and provides essential information for future therapeutics and diagnostics that can provide relief for those with this under-investigated disease.

Source: University of Connecticut

Menstrual Changes after COVID Vaccine

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A new analysis of offers the most comprehensive assessment so far of menstrual changes experienced by pre- and post-menopausal individuals in the first two weeks after being vaccinated against COVID. Published in the journal Science Advances, the study adds to the growing body of evidence that significant numbers of people experience this unexpected side effect.

“Menstruating and formerly menstruating people began sharing that they experienced unexpected bleeding after being administered a COVID vaccine in early 2021,” the scientists who led the study wrote. Because vaccine trials typically do not ask about menstrual cycles or bleeding, this side effect was largely ignored or dismissed.

Early reports about post-vaccination menstrual changes were largely brushed aside, said Kathryn Clancy, a professor of anthropology who led the research with Katharine Lee, another anthropology professor. Some clinicians said it was unclear how a vaccine could trigger such changes.

However, it is known that other vaccines – including those for typhoid, Hepatitis B and HPV – are sometimes associated with changes in menstruation, Prof Clancy said. The changes are more likely to be associated with an increase in immune-related inflammatory pathways, as opposed to any hormonal changes.

“We suspect that for most people the changes associated with COVID vaccination are short-term, and we encourage anyone who is worried to contact their doctor for further care,” Lee said. “We want to reiterate that getting the vaccine is one of the best ways to prevent getting very sick with COVID, and we know that having COVID itself can lead not only to changes in periods, but also hospitalisation, long COVID and death.”

The researchers used a survey to query people about their experiences after vaccination. Launched in April 2021, the survey asked for demographic and other information but focused on respondents’ reproductive history and experiences regarding menstrual bleeding. The team downloaded the data from the surveys on June 29, 2021. Only those who had not been diagnosed with COVID were included in the analysis, as COVID itself is sometimes associated with menstrual changes. Data from people aged 45–55 years was excluded to avoid the confounding of effect menstrual changes associated with perimenopause.

“We focused our analysis on those who regularly menstruate and those who do not currently menstruate but have in the past,” Prof Clancy said. “The latter group included postmenopausal individuals and those on hormonal therapies that suppress menstruation, for whom bleeding is especially surprising.”

A statistical analysis revealed that 42.1% of menstruating survey respondents reported a heavier menstrual flow after receiving the COVID-19 vaccine. Some experienced this in the first seven days but many others saw changes 8–14 days after vaccination. Roughly the same proportion, 43.6%, reported no alteration of their menstrual flow after the vaccine, and a smaller percentage, 14.3%, saw a mix of no change or lighter flow, the researchers report.

Because the study relied on self-reported experiences logged more than 14 days after vaccination, it cannot establish causality or be seen as predictive of people in the general population, Lee said. But it can point to potential associations between a person’s reproductive history, hormonal status, demographics and changes in menstruation following COVID vaccination.

For example, the analysis revealed that respondents who had experienced a pregnancy were most likely to report heavier bleeding after vaccination, with a slight increase among those who had not given birth. A majority of non-menstruating premenopausal respondents on hormonal treatment experienced breakthrough bleeding after receiving the vaccine. This side effect was common in respondents using long-acting reversible contraception and 38.5% of those undergoing gender-affirming hormone treatments reported this side effect.

Those who were older, and those who experienced fever or fatigue as a side effect of vaccination were also more likely than other groups to report heavier menstrual flow after vaccination. White respondents were slightly less likely to report heavier menstrual flow.

Those who had experienced endometriosis, menorrhagia, fibroids or other reproductive problems also were more likely to report a heavier menstrual flow post-vaccination, the team found. The largest single increase was in those who have been pregnant without a delivery.

While the uptick in menstrual flow for some people may be transitory and quickly resolve, unexpected changes in menstruation can still cause concern, Prof Lee said.

“Unexpected breakthrough bleeding is one of the early signs of some cancers in post-menopausal people and in those who use gender-affirming hormones, so experiencing it can make people worry and require expensive and invasive cancer-screening procedures,” Prof Lee said.

“This screening is very important so we can catch cancers early,” Prof Clancy said. “For diagnostic purposes, it would be helpful to know whether there are other causes for the bleeding.”

“We’d love to see future vaccine testing protocols incorporate questions about menstruation that go beyond screening for pregnancy,” Prof Lee said. “Menstruation is a regular process that responds to all kinds of immune and energetic stressors, and people notice changes to their bleeding patterns, yet we don’t tend to talk about it publicly.”

Source: University of Illinois at Urbana-Champaign

Maternal Phthalates Exposure Increases Preterm Birth Risk

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A National Institutes of Health study has found that pregnant women who were exposed to multiple phthalates during pregnancy had an increased risk of preterm birth. The most significant correlation was for a phthalate most commonly used in nail polish and cosmetics.

Used in a great variety of products such as cosmetics and food packaging, phthalates are endocrine-disrupting chemicals that are known to have a wide range of health effects on humans. This especially true of children, due to their impact on the developmental system, as well as the reproductive system.

Researchers analysed data from more than 6000 pregnant women in the US, and found that women with higher concentrations of several phthalate metabolites in their urine had increased risks of preterm birth.

“Having a preterm birth can be dangerous for both baby and mom, so it is important to identify risk factors that could prevent it,” said epidemiologist Kelly Ferguson, PhD, the senior author on the study published in JAMA Pediatrics.

Data from 16 US studies that included individual participant data on prenatal urinary phthalate metabolites (representing exposure to phthalates) as well as the timing of delivery. Researchers analysed data from a total of 6045 pregnant women who delivered between 1983-2018, 9% of whom delivered preterm. Phthalate metabolites were detected in more than 96% of urine samples.

Exposure to four of the 11 phthalates found in the pregnant women was associated with a 14–16% greater probability of having a preterm birth. The most consistent findings were for exposure to a phthalate that is used commonly in personal care products like nail polish and cosmetics.

Using statistical models to simulate interventions that reduce phthalate exposures, the researchers found that reducing the mixture of phthalate metabolite levels by 50% could prevent preterm births by 12% on average. Interventions targeting behaviours, such as trying to select phthalate-free personal care products (if listed on label), voluntary actions from companies to reduce phthalates in their products, or changes in standards and regulations could contribute to exposure reduction and protect pregnancies.

“It is difficult for people to completely eliminate exposure to these chemicals in everyday life, but our results show that even small reductions within a large population could have positive impacts on both mothers and their children,” said Barrett Welch, PhD, first author on the study.

Eating fresh, home-cooked food, avoiding processed food that comes in plastic containers or wrapping, and selecting fragrance-free products or those labeled ‘phthalate-free’, are examples of things people can do that may reduce their exposures. Changes to the amount and types of products that contain phthalates could also reduce exposures.

The researchers are undertaking further studies to better understand the mechanisms behind how phthalates affect pregnancy and to find ways for mothers to reduce their exposures.

Source: National Institutes of Health

Is Fathers’ Lifestyle a Risk Factor for Partners’ Preeclampsia?

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Although various maternal risk factors have been recognised, it is still unclear what causes preeclampsia, and some evidence suggests paternal risk factors such as obesity and cardiovascular disease. New research published in Acta Obstetricia et Gynecologica Scandinavica suggests that fathers’ characteristics and lifestyle however do not in fact play a significant role in their partners’ susceptibility to preeclampsia.

Preeclampsia (PE) is a complex vascular disorder in pregnancy characterized by new-onset hypertension and proteinuria after 20 weeks of gestation or new-onset PE-associated signs in the absence of proteinuria.

In this study, researchers examined questionnaire data from 586 men who had fathered a preeclamptic pregnancy and 660 control men who had fathered a non-preeclamptic pregnancy. Fathers in the former group more often reported preeclampsia in a previously fathered pregnancy, but there were no differences in the socioeconomic background or health history of the preeclamptic and control fathers or their parents.

“Importance of paternal genetic factors has been demonstrated in their partners’ susceptibility to preeclampsia, but the role of paternal phenotype and lifestyle is still not well understood. Both paternal genotype and phenotype need to be addressed in future studies,” said co-author Noora Jaatinen, MD, a University of Turku PhD student.

Source: Wiley