Category: Obstetrics & Gynaecology

Lasting Postpartum Mental Health Problems may be Tied to Immune Response

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Women with prolonged mental health problems up to three years after childbirth may be suffering from irregular immune system responses, suggests new research published in the American Journal of Reproductive Immunology.

“We found that women who had clinically elevated symptoms of depression, anxiety, and/or post-traumatic stress disorder (PTSD) two to three years after delivery had genetic evidence of a higher prevalence of immune system defence mechanism activation,” said Eynav Accortt, PhD, principal investigator of the study and director of the Reproductive Psychology Program at Cedars-Sinai.

“These women also appeared to have a reduction in the activity of genes related to antiviral immune responses that can offer the body protection from pathogens,” said Accortt, a clinical psychologist.

Roughly 1 in 8 women experience significant symptoms of perinatal mood and anxiety disorders that can interfere with health and quality of life. Much of the research into maternal mental health to date has focused on the perinatal period and the first year after childbirth.

Cedars-Sinai investigators surveyed 33 women about their mental health over a longer period, two to three years after giving birth. Study participants also provided a blood sample, and scientists performed bioinformatic analyses of differential gene expression.

“Delayed or persistent postpartum anxiety, depression and PTSD is an area that is woefully understudied,” said study co-author Sarah Kilpatrick, MD, PhD, chair of the Department of Obstetrics and Gynecology at Cedars-Sinai.

“In this preliminary research, we have identified genetic differences related to inflammation when comparing women experiencing prolonged symptoms of mood and anxiety disorders to those who did not report poor mental health. Additional studies will be needed for a deeper dive into the role inflammation may play in postpartum mental illness,” said Kilpatrick.

One of the research aims is to design a blood test to identify those at high risk for serious and prolonged postpartum mood disorders, according to Accortt.

“A blood test could help us develop early interventions that provide medical and mental health treatments and support. We want to figure out why some women are at greater risk for depression, anxiety and PTSD. No one should have to suffer for years after childbirth,” said Accortt.

Source: Cedars-Sinai Medical Center

No Link between Benzodiazepines Use in Pregnancy and Offspring Autism, ADHD

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A large-scale study published in JAMA Network has found no link between benzodiazepines use in pregnancy and subsequent autism spectrum disorder (ASD) or attention-deficit/hyperactivity disorder (ADHD) diagnoses in offspring. When comparing siblings, benzodiazepines use had no effect on ASD or ADHD risk, indicating that the mother’s genetics partly explained the increased risk.

Some 10–30% of pregnant women experience mental disorders, including mood or anxiety spectrum disorders, for which benzodiazepine agents are sometimes prescribed; this occurs in an estimated 1.9% of pregnancies globally.

The safety of these agents to the developing foetus and newborn has been called into question, since benzodiazepines are able to cross the placenta and have been found to be present in amniotic fluid and breast milk. The US FDA includes in the category of possible harm to the foetus.

While rodents studies have tested benzodiazepine exposure during the first trimester of pregnancy, investigations of neurodevelopmental outcomes in humans, such as ASD and ADHD, have been lacking.

One study found no significantly increased risks of ADHD symptoms or fine or greater motor deficits. Those researchers suggested the disorder resulting in benzodiazepine use might partly explain the increased risks. Maternal depressive and anxiety symptoms in pregnancy have also been linked to increased ADHD risk in children.

From the Taiwanese national health database, of over 1 .5 million children born full term who were younger than 14 years of age and followed up to 2017; 5.0% had been exposed to benzodiazepines in utero.

However, no differences were found with unexposed sibling controls during the same time frame for ADHD or ASD.

The researchers concluded that their results “challenge current assumptions of a potential association of neurodevelopmental disorders with maternal benzodiazepine use before or during pregnancy. Better identification of maternal mental health concerns, as well as possible interventions or provisions of guidance to build better nurturing and raising environments for newborns at risk, may be relevant to the prevention of adverse outcomes of neurodevelopmental disorders.”

Smoke and Fumes from Indoor Cooking Fires an Eclampsia Risk

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In a study published in the International Journal of Gynecology & Obstetrics, UK researchers have uncovered an association between the rate of eclampsia and the number of deaths caused by indoor household pollution, mostly from cooking and heating fires.

More commonly seen in low- and middle-income countries commonly using solid fuels, such as wood and charcoal, indoor household pollution has been proven to increase the risk of adverse birth outcomes, including placental hypoxia.

The researchers evaluated more than 2690 cases of eclampsia in Ethiopia, Haiti, India, Malawi, Sierra Leone, Uganda, Zambia and Zimbabwe, and found a significant correlation between deaths due to indoor household pollution and eclampsia rates – and the correlation was even more prominent when eclampsia occurred at home.

King’s College London’s Professor Andrew Shennan, one of the lead authors on the paper, said the findings demonstrate how air pollution can impact vulnerable populations the most.

“In-house cooking and household pollution may increase the risk of seizures. We believe that less oxygen will get to the mother’s brain, and this may trigger a fit in women who already have pre-eclampsia” he said.

“We are lucky to have such a large dataset of women with eclampsia, as it only occurs in 1% of women with pre-eclampsia. This has allowed us to uncover this new finding.

“This could help explain observed inequalities in maternal healthcare in low- and middle-income countries.”

In a previous study by King’s College London, scientists found that 94% of maternal deaths occur in low- and middle-income countries, with 22% due to hypertensive disorders like eclampsia.

Professor Shennan added: “Knowing why women have these severe outcomes allows us to reduce the risk of eclampsia and work out how to save lives.

“We have large programmes of work in India, Sierra Leone and Zambia where many women have complications related to high blood pressure. Our current research is aimed at identifying the women at risk but now we are looking at ways to reduce risk, including earlier delivery. This data will help us to give advice about avoiding risk at home.”

The researchers next plan to explore whether climate change increases the prevalence of pre-eclampsia or increases the morbidity from serious manifestations such as eclampsia.

Source: King’s College London

Phthalates in Everyday Products do Cause Uterine Fibroids

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For the first time, a study published Proceedings of the National Academy of Sciences (PNAS) has shown a causal association between environmental phthalates and the increased growth of uterine fibroids, the most common tumours among women.

Manufacturers use environmental phthalates in numerous industrial and consumer products, and they’ve also been detected in medical supplies and food. Although they are known to be toxic, they are currently unbanned in the US.

“These toxic pollutants are everywhere, including food packaging, hair and makeup products, and more, and their usage is not banned,” said corresponding study author Dr Serdar Bulun at Northwestern University. “These are more than simply environmental pollutants. They can cause specific harm to human tissues.”

Up to 80% of all women may develop a fibroid tumour during their lifetime, Bulun said. One-quarter of these women become symptomatic with excessive and uncontrolled uterine bleeding, anaemia, miscarriages, infertility and large abdominal tumours necessitating technically difficult surgeries.

The new study found women with a high exposure to certain phthalates such as DEHP (used as a plasticiser to increase the durability of products such as shower curtains, car upholstery, lunchboxes, shoes and more) and its metabolites have a high risk for having a symptomatic fibroid.

Prior epidemiological studies have consistently indicated an association between phthalate exposure and uterine fibroid growth, but this study explains the mechanisms behind that link. The scientists discovered exposure to DEHP may activate a hormonal pathway that activates an environmentally responsive receptor (AHR) to bind to DNA and cause increased growth of fibroid tumors.

“Interestingly, AHR was cloned in the early ’90s as the receptor for dioxin, the key toxin in the agent orange,” Bulun said. “The use of agent orange during the Vietnam war caused significant reproductive abnormalities in the exposed populations; and dioxin and AHR were thought to be responsible for this.”

This new study, Bulun said, provides further evidence to support these theories.

Source: Northwestern University

Even in Remission, IBD is a Risk Factor for Preterm Birth

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Inflammatory bowel disease is a risk factor for giving birth preterm even when in apparent disease remission, according to a study published in the journal eClinicalMedicine. If corroborated, the results may eventually affect recommendations for women with ulcerative colitis wishing to conceive.

Inflammatory bowel disease (IBD) is chronic inflammatory disease with a prevalence of approximately 0.5%. IBD, which includes ulcerative colitis and Crohn’s disease, and – unlike irritable bowel syndrome (IBS) – causes visible damage to the mucosa lining the intestines. IBD is characteristic for its recurrent tendency for symptoms to relapse, followed by periods of remission.

Onset of IBD commonly occurs at age 15–30, so questions about its impact on pregnancy and the foetus are common. IBD has previously been linked to negative birth outcomes, such as preterm birth (< 37 weeks of pregnancy), mainly in women showing signs of active disease.

Also, women without obvious IBD activity often have microscopic inflammation in the intestinal mucosa. Until now, however, it has been unknown whether even microscopic inflammation may be associated with risks in pregnancy.

Higher risk of preterm birth

The present study, shows that microscopic inflammation in IBD, especially ulcerative colitis, is linked to an elevated risk of giving birth prematurely.

Among babies born to women with microscopic inflammation due to IBD, 9.6% were preterm, while 6.5% of children were born preterm to women without microscopic inflammation of IBD. This corresponds to a relative risk increase of 46 percent. Microscopic inflammation was not clearly associated with other adverse pregnancy outcomes, such as growth restriction.

The results are based on register data on women in Sweden, diagnosed with IBD in 1990–2016, in whom information was available on the microscopic appearance of the intestine shortly before pregnancy. The study included 1223 children of women with microscopic IBD inflammation of the intestine and 630 children of women with IBD but with microscopically healed intestinal mucosa.

Through register linkages, data were also retrieved from several national health registers, such as the Swedish Medical Birth Register and the Swedish Quality Register for Inflammatory Bowel Desiease (SWIBREG).

Prospect of new treatment targets

“Our results suggest that IBD treatment aimed at not merely alleviate symptoms of IBD, but also microscopically heal the intestine, can reduce the risk of giving birth preterm,” sayd first author and corresponding author is Karl Mårild, associate professor of paediatrics at Sahlgrenska Academy, University of Gothenburg. “If our results hold up in future studies, they may therefore be the basis for recommendations to confirm microscopic healing before pregnancy, to reduce such risks.”

“Even a modestly increased relative risk of preterm birth is important, given that preterm birth can greatly affect the child’s health in both the short and the long term. Preterm birth is still one of the most common causes of death for children under the age of five in Sweden,” Karl Mårild concludes.

Source: University of Gothenburg

EU Adds Heavy Menstrual Bleeding as Side Effects of Comirnaty and Spikevax

Covid vaccines
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The European Medicines Agency (EMA) recommended that heavy menstrual bleeding should be added to the product information as a side effect of unknown frequency of the mRNA COVID vaccines Comirnaty (Pfizer/BioNtech) and Spikevax (Moderna).

Heavy menstrual bleeding may be defined as bleeding characterised by an increased volume and/or duration which interferes with the person’s physical, social, emotional and material quality of life. Cases of heavy menstrual bleeding have been reported after the first, second and booster doses of Comirnaty and Spikevax.

The EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) assessed this safety signal after reviewing the available data, including cases reported during clinical trials, cases spontaneously reported in Eudravigilance and findings from the medical literature.

After a review of the available data, the PRAC concluded that there is at least a reasonable possibility that the occurrence of heavy menstrual bleeding is causally associated with these vaccines and therefore recommended the update of the product information.

The available data reviewed involved mostly cases which appeared to be non-serious and temporary in nature.

There is no evidence to suggest the menstrual disorders experienced by some people have any impact on reproduction and fertility. Available data provides reassurance about the use of mRNA COVID vaccines before and during pregnancy. A review carried out by EMA’s Emergency Task Force showed that mRNA COVID vaccines do not cause pregnancy complications for expectant mothers and their babies, and they are as effective at reducing the risk of hospitalisation and deaths in pregnant people as they are in non-pregnant people.

Source: European Medicines Agency

Hopeful IVF Parents Should Skip the Drinks

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In a recent analysis published in Acta Obstetricia et Gynecologica Scandinavica, researchers found no link between women’s caffeine consumption and pregnancy or live birth rate after fertility treatments – but alcohol consumption was linked to decreased pregnancy rate after treatments with more than 84g of alcohol a week (approximately 7 standard drinks).

The link held true for their spouses as well: men’s alcohol consumption was associated with decreased live birth rate after fertility treatments in women when weekly consumption was greater than 84g.

The researchers searched the available literature and found a total of 7 studies on caffeine consumption and 9 studies on alcohol consumption were included, with a total of 26 922 women and/or their spouse who underwent fertility treatment.

Compared with those abstaining from alcohol, the chance of achieving a pregnancy after fertility treatment decreased by 7% for women who consumed 84g of alcohol per week, and the chance of partners achieving a live birth decreased by 9% for men who consumed 84g of alcohol per week.

“Couples should be aware that some modifiable lifestyle factors such as drinking habits may affect their fertility treatment outcomes. But how these factors impact the reproductive system still needs more research to elucidate,” said corresponding author Yufeng Li, MD, of Tongji Hospital, in China.

Source: Wiley

Intermittent Fasting does not Impact Female Sex Hormones

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Intermittent fasting has been shown to be an effective way to lose weight, but critics have worried that the practice may have a negative impact on women’s reproductive hormones. Now, researchers bring new evidence to the table in a study published in Obesity.

The researchers, led by Krista Varady, University of Illinois Chicago professor of nutrition, followed a group of pre- and post-menopausal obese women for a period of eight weeks on the ‘warrior diet’ method of intermittent fasting.

The warrior diet prescribes a time-restricted feeding window of four hours per day, during which dieters can eat without counting calories before resuming a water fast until the next day.

They measured the differences in hormone levels, obtained by analysing blood sample data, in groups of dieters who stuck to four- and six-hour feeding windows against a control group that followed no diet restrictions.

Varady and her team found that levels of sex-binding globulin hormone, a protein that carries reproductive hormones throughout the body, was unchanged in the dieters after eight weeks. The same held true for both testosterone and androstenedione, a steroid hormone that the body uses to produce both testosterone and oestrogen.

However, dehydroepiandrosterone or DHEA, a hormone that fertility clinics prescribe to improve ovarian function and egg quality, was significantly lower in both pre-menopausal and post-menopausal women at the end of the trial, dropping by about 14%.

While the drop in DHEA levels was the most significant finding of the study, in both pre- and post-menopausal women, DHEA levels remained within the normal range by the end of the eight-week period.

“This suggests that in pre-menopausal women, the minor drop in DHEA levels has to be weighed against the proven fertility benefits of lower body mass,” Varady said. “The drop in DHEA levels in post-menopausal women could be concerning because menopause already causes a dramatic drop in estrogen, and DHEA is a primary component of estrogen. However, a survey of the participants reported no negative side effects associated with low estrogen post-menopause, such as sexual dysfunction or skin changes.”

As an added benefit, since high DHEA has been linked to breast cancer risk, Varady said a moderate drop in levels might be helpful in reducing that risk for both pre- and post-menopausal women.

The study measured levels of oestradiol, oestrone and progesterone as well, but only in post-menopausal women, due to the changing levels of these hormones throughout pre-menopausal women’s menstrual cycles. Among post-menopausal women, there was no change in these hormones at the end of eight weeks.

Women in both the four-hour and six-hour dieting groups experienced weight loss of 3% to 4% of their baseline weight throughout the course of the study, compared with the control group, which had almost no weight loss. The dieters also saw a drop in insulin resistance and in biomarkers of oxidative stress.

Perimenopausal women, who are typically in their 40s, were excluded from the study.

Still, Varady said, “I think this is a great first step. We’ve observed thousands of pre- and post-menopausal women through different alternate-day fasting and time-restricted eating strategies. All it’s doing is making people eat less. By shortening that eating window, you’re just naturally cutting calories. Much of the negative information on intermittent fasting reported has come from studies on mice or rats. We need more studies to look at the effects of intermittent fasting on humans.”

Source: University of Illinois Chicago

Diet and Exercise for Obese Mothers Lowers Cardiovascular Risk in Infants

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A new study, published in the International Journal of Obesity, found that 3-year-old children were more likely to exhibit risk factors for future heart disease if their mother was clinically obese during pregnancy. A behavioural lifestyle intervention reduced this risk.

There is increasing evidence to suggest that obesity in pregnancy is associated with cardiometabolic dysfunction in children, and that serious cardiovascular disease may begin in the womb.

The UPBEAT trial, conducted at Guy’s and St Thomas’ NHS Foundation Trust, randomised women with obesity (a BMI of over 30 kg/m2) in early pregnancy to a diet and exercise intervention or to standard pregnancy care. The intervention included one-to-one counselling, restricting dietary intake of saturated fat, eating foods with a low glycaemic index such as vegetables and legumes, moderate and monitored physical activity and tools to record exercise. The intervention arm saw improvements in weight gain in pregnancy, physical activity, a healthier diet, and a healthier metabolic profile across pregnancy.

Follow-up of the children at age three showed that children of women with clinical obesity had evidence of cardiac remodelling, a risk factor for future cardiovascular disease. Changes included increased heart muscle thickness, elevated resting heart rate, evidence of early impairment to the heart’s relaxation function and increased sympathetic nerve activity compared to women of normal weight. The children of women who were allocated to the intervention arm were protected from these early changes in heart structure and function.

Study lead Dr Paul Taylor, from King’s College London, said: “Maternal obesity appears to adversely impact the developing foetal nervous system and foetal heart development which is apparent up to 3 years-of-age. A complex lifestyle intervention in pregnancy was associated with protection against cardiac remodelling in infants. We can hypothesise that these changes to the heart and its function will get worse over time, putting the child at increased risk of cardiovascular disease in the future.”

The study suggests that maternal obesity may have a lasting impact on the child’s cardiovascular health. Promoting dietary changes and physical activity during pregnancy may reduce this risk.

Source: King’s College London

Single-stranded Suture Threads could Prevent Infection Complications in Pregnancy

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Source: Pixabay

Women at risk of pregnancy loss who need a specialist surgical procedure could benefit from a single-stranded suture thread to reduce risk of infection, results from the C-STICH clinical trial found which were published in The Lancet. 

The trial involved more than 2000 expectant mothers who needed a procedure called a cerclage, where a purse string suture is placed around the cervix during their pregnancy. Women were randomly allocated to have the surgical procedure performed using either a single stranded thread or a braided thread.

Researchers tested whether there would be any difference in miscarriage or stillbirth, due to an increased risk of infection, from using a braided suture thread. The research shows that single stranded sutures could potentially improve outcomes for mothers at risk of preterm birth.

The team, led by researchers from the University of Birmingham and Birmingham Women’s and Children’s Hospital, found that the mothers treated with single stranded threads had no differences in pregnancy loss or preterm birth but reported fewer instances of infection and sepsis. This could have important implications for the health outcomes of mothers and babies who are treated with a cervical cerclage in their pregnancy.

Dr Vicky Hodgetts-Morton, NIHR Clinical Lecturer in Obstetrics at the University of Birmingham and Birmingham Women’s Hospital explained the implications of the trial results. Dr Hodgetts-Morton said:

“Preterm birth is a significant problem, complicating approximately one in ten pregnancies around the world. The consequences of preterm birth may be significant with some babies being born too early to survive, and those that survive are at increased risk of health complications. One cause for preterm birth is cervical insufficiency, occurring in 0.5% to 1% of pregnant women for which the placement of a vaginal cervical cerclage can be an effective treatment.

“Suture thread choice has the potential to improve how well a cerclage works in preventing miscarriage, stillbirth and preterm birth. Both single stranded and braided threads are commonly used to perform cerclages and our findings show no differences in pregnancy loss and preterm birth. The C-STICH trial results did show an increased risk of infections in labour and around the time of delivery with braided threads and this supported our hypothesis that a single stranded thread could reduce the risk of infection developing during the pregnancy.”

Source: University of Birmingham