Category: Obstetrics & Gynaecology

Limited Evidence for Menstrual Changes After COVID Vaccination

Photo by Gustavo Fring on Pexels

Results from a Swedish study of nearly three million women and girls published by The BMJ found that there was no evidence of an increased risk of post-COVID vaccination menstrual changes that were significant enough for healthcare interaction.

The researchers found only weak and inconsistent associations were found between COVID vaccination and contact with healthcare for postmenopausal bleeding. These were even less consistent for menstrual disturbance and premenstrual bleeding.

These findings do not provide any substantial support for a causal association between COVID vaccination and diagnoses related to menstrual or bleeding disorders, say the researchers.

Many women have reported changes to their periods after a COVID vaccination, such as the number of days they bleed and the heaviness of the flow. Self-reporting may capture events that normally would not result in a healthcare contact but may still be sufficiently disturbing to be relevant for the affected women. But calculating the strength of a potential association based on self reports can be unreliable.

To address this, researchers in Sweden drew on high quality health registry data to evaluate the risks of menstrual disturbance and bleeding after COVID vaccination in 2 946 448 women and girls aged 12-74 years from December 2020 to February 2022.

Contact with healthcare included primary care visits, specialist outpatient visits, and days of hospital stay related to menstrual disturbance or bleeding before or after menopause.

Risks were assessed by vaccine (Pfizer-BioNTech, Moderna, or Oxford-AstraZeneca) and dose (unvaccinated and first, second, and third dose) over two time windows (1-7 days, considered the control period, and 8-90 days).

In the main analysis, more than 2.5 million (88%) of women received at least one covid-19 vaccination and over 1.6 million (64%) of vaccinated women received three doses during the study period.

The highest risks for bleeding in postmenopausal women were seen after the third dose in the 1-7 days risk window (28%) and in the 8-90 days risk window (25%).

Adjusting for socioeconomic factors, previous healthcare use, and for several specific medical conditions had only a modest effect on these results.

Analyses of individual vaccines and risk of postmenopausal bleeding suggested a 23-33% increased risk after 8-90 days with Pfizer-BioNTech, and Moderna after the third dose, but a less clear association with Oxford-AstraZeneca.

In premenopausal women, weak associations were found for menstrual disturbance or bleeding after vaccination with any dose (13% or 8% after 1-7 days and 6% or 1% after 8-90 days, respectively). However, adjusting for other factors almost completely removed these weak associations, suggesting that a causal effect is unlikely.

These are observational findings and the authors point to several limitations, including the fact that the time between onset, start of symptoms, and date of healthcare contact might be considerable, making the interpretation of effect of different risk windows challenging. 

But this was a large study with near complete follow-up, using mandatory data from nationwide registers.

As such, they say: “We observed weak and inconsistent associations between SARS-CoV-2 vaccination and healthcare contacts for postmenopausal bleeding, and even less consistent for menstrual disturbance, and premenstrual bleeding.”

They add: “These findings do not provide any substantial support for a causal association between SARS-CoV-2 vaccination and healthcare contacts related to menstrual or bleeding disorders.”

Source: The BMJ

Preterm Births Concern Raised Over New Maternal RSV Vaccine

Experts have called for further scrutiny of a new Pfizer vaccine given during pregnancy to prevent respiratory infection in infants, after trials of a similar GSK vaccine were stopped after increased preterm birth and infant deaths. Pfizer says its vaccine is safe and effective, but experts contacted as part of an investigation published by The BMJ say that Pfizer’s trial data should be reviewed in light of the trend for preterm births seen in GSK’s trial.

Pfizer’s maternal RSV vaccine aims to protect infants from severe illness caused by the respiratory syncytial virus (RSV). RSV is very common but can be fatal, especially in young children. In 2019, an estimated 3.6% of all deaths worldwide in children aged 1-6 months were due to RSV, with 97% of these deaths occurring in low and middle income countries.

The vaccine has not yet been approved for use, but a decision by the US Food and Drug Administration is expected by August. The European Medicines Agency is also set to make a decision about the vaccine later this year.

In February 2022, GSK halted vaccination in its phase 3 trials of its maternal RSV vaccine after finding an increased risk of preterm birth in vaccinated mothers, mainly in low and middle income countries.

Pfizer published the results of an interim analysis of its phase 3 trial last month, saying that the vaccine was effective against medically attended severe RSV in children and that no safety concerns were identified.

And while the difference in preterm births in the Pfizer trials was not statistically significant, the results have raised concerns about a possible increase in preterm births, and now experts are calling for further analyses of the data and post-approval monitoring of the vaccine should the FDA approve it.

“My interpretation of all these data is that there may be a safety signal for preterm births that should be followed up on,” said Klaus Überla, director of the Virological Institute of the University Hospital Erlangen and member of the RSV working group of the Standing Committee on Vaccination (STIKO), which develops national recommendations for the use of licensed vaccines in Germany. 

And a scientist at the National Institutes of Health (NIH) said the Pfizer data should be analysed using more sensitive measures such as average birth weight and subgroup analyses to detect possible signals.

Meanwhile, Cody Meissner, professor of paediatrics and medicine at the Dartmouth Geisel School of Medicine and consultant in the US Centers for Disease Control and Prevention (CDC)’s maternal RSV working group, predicts that possible adverse effects such as premature births will be “closely monitored” in assessment programs by FDA and CDC.  “We need a safe vaccine,” he added.

Pfizer did not respond when asked about a possible increase in preterm births associated with its vaccine, but told The BMJ that “no imbalance of neonatal deaths was observed” in its phase 3 trial. 

In a linked editorial, researchers point to challenges for RSV vaccine development and the main approaches to protection currently being pursued. 

They argue that, while the burden of illness caused by RSV is substantial worldwide, it is particularly important that new vaccines and other prevention strategies are available to infants in low and middle income countries, where the greatest illness and deaths occur.

And they say further research is urgently needed “to identify the best prevention strategies for low and middle income countries, where affordability is paramount and timing of administration is complicated by the lack of predictable seasonal RSV epidemics.”

Source: EurekAlert!

Sons Born to Women with PCOS Can Also Encounter Health Problems

Photo by Annie Spratt on Unsplash

Sons of women with polycystic ovary syndrome (PCOS) have a twofold increased risk to develop obesity, according to a study published in Cell Reports Medicine. The findings highlight a previously unknown risk of passing PCOS-related health problems across generations through the male side of a family, say the the researchers from Karolinska Institutet.

PCOS is caused by overproduction of testosterone by the ovaries and affects around 15% of women of childbearing age worldwide, impacting fertility. In addition, the disease is associated with various health problems such as diabetes, obesity, and mental illness. 

Daughters of women with PCOS have a fivefold risk of developing the same disease. Although it is not yet clear how sons of women with PCOS are affected, research suggests that they are more likely to have weight and hormone problems

The researchers used both registry data and mouse models in the newly published study to determine if and how PCOS-like traits are passed from mothers to their sons. Just over 460 000 sons born in Sweden between July 2006 and December 2015 were included in the registry study. Of these, roughly 9000 had mothers with PCOS. The researchers then identified which of the children were obese. 

“We discovered that sons of women with PCOS have a twofold increased risk of obesity and of having high levels of “bad” cholesterol, which increases the risk of developing insulin resistance and type 2 diabetes later in life”, says study leader Elisabet Stener-Victorin, professor at Karolinska Institutet. 

These findings were confirmed in the mouse study, where the researchers examined male offspring of female mice that before and during pregnancy were fed either a standard diet or a diet rich in fat and sugar, and were exposed to high levels of the male sex hormone dihydrotestosterone during pregnancy to mimic the pregnancy of normal weight individuals and obese women with PCOS. 

The male mice were then fed a standard diet until adulthood when their fat distribution and metabolism were examined. 

“We could see that these male mice had more fat tissue, larger fat cells, and a disordered basal metabolism, despite eating a healthy diet”, says Elisabet Stener-Victorin.

To investigate the reproductive function of the offspring and whether physiological characteristics can be passed on from generation to generation, the first-generation male mice were mated with healthy female mice that were not exposed to male sex hormones or a diet rich in fat and sugar. The whole process was repeated in the second generation to reach the third generation which is the first generation that was not affected by the mother condition.  
 
“Through these experiments, we can show that obesity and high levels of male hormones in the woman during pregnancy can cause long-term health problems in the male offspring. Their fat tissue function, metabolism, and reproductive function deteriorate, which in turn affects future generations”, says Qiaolin Deng, associate professor at the same department and one of the researchers behind the study.
 
“These findings are important because they highlight the risk of passing health problems down through the male side of a family, highlight the risk of passing this kind of health problem, and they may help us in the future to find ways to identify, treat and prevent reproductive and metabolic diseases at an early stage,” says Elisabet Stener-Victorin.

Source: Karolinska Institutet

Labour Induction in 39th Week Does not Decrease Risk of Needing Caesarean

In recent years, experts have debated the benefits of labour induction once at a certain stage of pregnancy. But a new US study suggests that inducing labour at the 39th week of pregnancy for those having their first births with a single baby in a head down position, or low risk, doesn’t necessarily reduce the risk of caesarean births. In fact, for some, it may even have the opposite effect if hospitals don’t take a thoughtful approach to induction policies.

“Some people in the field have suggested that after 39 weeks of gestation, medical induction should be standard practice,” said lead author Elizabeth Langen, MD, a high-risk maternal fatal medicine physician and researcher at University of Michigan Health Von Voigtlander Women’s Hospital, of Michigan Medicine.

“We collaborated with peer hospitals to better understand how labour induction may influence caesarean birth outcomes in real world maternity units outside of a clinical trial. In our study sample, we found inducing labour in this population of women and birthing people did not reduce their risk of caesarean birth.”

The new research, published in the American Journal of Perinatology, was based on more than 14 135 deliveries in 2020 analysed through a statewide maternity care quality collaborative registry.

Results conflict with national trial findings

The study was conducted in response to published research in 2018 from a multicentre trial known as “ARRIVE” (A Randomized Trial of Induction Versus Expectant Management.)

Findings from ARRIVE indicated that medical induction at 39 weeks gestation in first time low risk pregnancies resulted in a lower rate of caesarean deliveries compared to expectant management – or waiting for labour to occur on its own or for a medical need for labour induction.

Michigan researchers mimicked the same framework used in the national trial and analysed data from the collaborative’s data registry, comparing 1558 patients who underwent a proactively induced labour versus 12 577 who experienced expectant management. However, their results failed to support a link between elective induced labour in late pregnancy and a reduction in caesarean births.

In fact, results from the general Michigan sample were contradictory to the ARRIVE trial: Women who underwent elective induction were more likely to have a caesarean birth compared with those who underwent expectant management (30% versus 24%.)

In a subset of the sample, matching patient characteristics for a more refined analysis, there were no differences in c-section rates. Authors noted that time between admission and delivery was also longer for those induced.

Expectantly managed women were also less likely to have a postpartum haemorrhage (8 % versus 10 %) or operative vaginal delivery (9 % versus 11 %), whereas women who underwent induction were less likely to have a hypertensive disorder of pregnancy (6 % versus 9%.) There were no other differences in neonatal outcomes.

Authors point to several possible explanations for why the two studies had conflicting results. One key difference was that the Michigan study collected data after births for the purpose of quality improvement in a general population of low-risk births. The ARRIVE trial, however, used data collected in real time as part of a research study.

A significant difference between clinical trial participants and the general birthing population, Low says, may revolve around shared decision-making. Before trial enrolment, participants undergo a thorough informed consent process from trained study team members.

For the ARRIVE trial, this meant 72% of women approached to be in the study declined participation. Meanwhile, previous research has indicated that women in the general U.S. population often may feel pressured into agreeing to have their labour induced.

“Better outcomes may have occurred in the trial because the participants were fully accepting of this process,” Low said.

“Further research is needed to identify best practices to support people undergoing labour induction,” she added. “Prior to initiating an elective induction of labour policy, clinicians should also ensure resources and a process to fully support shared decision-making.”

Source: Michigan Medicine – University of Michigan

Preterm Birth and Size Linked to Adult Fibrillation Risk

Photo by Hush Naidoo on Unsplash

A new study published in JAMA Pediatrics showed an association between being born preterm or large for gestational age and increased risks of atrial fibrillation later in life. Being small for gestational age at birth was only associated with an increased risk of atrial fibrillation up to the age of 18.

The incidence of atrial fibrillation in the young has increased over the past few decades, from low levels.

To date there have been little or mixed findings regarding the risk of atrial fibrillation in those with adverse birth outcomes. Atrial fibrillation increases the risk of stroke and other cardiovascular conditions, and is the most common form of cardiac arrhythmia. It mainly affects the middle-aged and the elderly. The estimated incidence in the young is low, 0.12 to 0.16%.

Low incidence in the young

A collaborative study involving researchers from Karolinska Institutet has now investigated the risk of atrial fibrillation according to preterm birth and foetal growth.

“Atrial fibrillation at a young age may involve a heavy socioeconomic burden for the affected individuals and we need to learn more about the underlying causes of the disease,” says first author Fen Yang, doctoral student at Karolinska Institutet. “Our findings may highlight the need to monitor and prevent the disease in individuals with an elevated risk of atrial fibrillation.”

“We found that individuals born preterm and those who were large for gestational age at birth had a slightly higher risk of developing atrial fibrillation up to middle-age than those with corresponding normal birth outcomes,” says principal investigator Krisztina László, associate professor at the Department of Global Public Health, Karolinska Institutet, and senior lecturer at the Department of Public Health and Caring Sciences at Uppsala University. “Individuals who were small for gestational age at birth had an increased risk of atrial fibrillation up to the age of 18, but not later in adulthood.”

The risk increase was 30% for individuals born preterm, 55% for individuals who were large at birth and 71% for individuals who were both preterm and large for gestational age at birth.

Eight million participants

The results of the study are based on statistical analyses of over eight million births from Danish (1978–2016), Finnish (1987–2014) and Swedish (1973–2014) medical birth registries who were followed for incident atrial fibrillation in the national patient and cause of death registries up to 2021. The results were compared with siblings in the same families. Since the study was observational, no causal relationships could be ascertained.

The researchers say that future studies may investigate the association between preterm birth, foetal growth, and the risk of atrial fibrillation up to old age.

Source: Karolinska Institutet

Chinese Traditional Medicine in Pregnancy Linked to Increased Congenital Malformations

A new study published in the journal Acta Obstetricia et Gynecologica Scandinavica has uncovered an association between the use of traditional Chinese medicine during pregnancy and congenital malformations, including heart defects, in children.

In the prospective study, 16 751 women who received obstetrics care from hospitals in China completed a survey on their use of traditional Chinese medicine before and during pregnancy. Among foetuses, there were 273 congenital malformations.

Foetuses exposed to traditional Chinese medicine had 2.1-times higher odds of developing congenital malformations compared with those without exposure. There were significant associations with congenital malformations in women with early pregnant use of traditional Chinese medicine and for those who used two or more types of these products.

“To improve traditional Chinese medicine, we should pay more attention to its hazards – especially the identification of teratogenic ingredients – while also evaluating its therapeutic effects,” said corresponding author Jiang-Nan Wu, of Obstetrics and Gynecology Hospital of Fudan University, in China.

Source: Wiley

Processed Foods Increase Miscarriage Risk; Fruits Reduce it

A preconception and early-pregnancy diet that contains lots of fruit, vegetables, seafood, dairy, eggs and grain may be associated with reducing risk of miscarriage, suggests a new review of research in the journal Fertility and Sterility.

University of Birmingham researchers analysed 20 studies on eating habits in the months before and shortly after conceiving a baby to see whether these studies showed evidence of association with a lower or higher chance of miscarriage. The team conclude that there is evidence to suggest a diet rich in fruit, vegetables, seafood, dairy products, eggs and grain reduces miscarriage risk.

Not surprisingly, these are foods which typically make up ‘healthy’ well-balanced diets, with previous evidence showing that eating a well-rounded diet which is rich in vitamins and minerals during pregnancy is important.

The research review found that, when compared to low consumption, high intake of fruit may be associated with a 61% reduction in miscarriage risk. High vegetable intake may be associated with a 41% reduction in miscarriage risk. For dairy products it is a 37% reduction, 33% for grains, 19% for seafood and eggs.

Led by Dr Yealin Chung, researchers also looked at whether pre-defined dietary types, such as the Mediterranean Diet or Fertility Diet could also be linked to miscarriage risk. They could not find evidence that following any of these diets lowered or raised risk.

However, a whole diet containing healthy foods overall, or foods rich in antioxidant sources, and low in pro-inflammatory foods or unhealthy food groups may be associated with a reduction in miscarriage risk for women.

A diet high in processed food was shown to be associated with doubling of miscarriage risk.

The studies included in the analysis focused on the peri-conception period, which is before and during the first 3 months of pregnancy. Data collected from a total of 63 838 healthy women of reproductive age was included, with information on their diets typically collected through food frequency questionnaires for each study.

Dr Chung explains:

“Miscarriage is common, with estimates suggesting 1 in 6 pregnancies end in miscarriage, and there are many known causes, from problems with the baby’s chromosomes to infections in the womb.

“Yet nearly 50% of early pregnancy losses remain unexplained and in the absence of a cause, parents often turn to their healthcare providers for guidance on the best ways to be as healthy as possible and reduce the risk of future miscarriages.

“There’s a growing body of evidence to show that lifestyle changes – including changes to diet, stopping smoking and not drinking alcohol – before conceiving and in your pregnancy’s early stages – may have an impact.”

Source: University of Birmingham

Lower-dose Hormonal Contraceptives may be Possible, Study Suggests

Photo: Reproductive Health Supplies Coalition on Unsplash

The dosage of hormones in common contraceptives could be reduced by as much as 92% and still effectively suppress ovulation, according to a computational model from University of the Philippines Diliman which is described in PLOS Computational Biology.

Constant dosage and nonconstant dosage comparison. The shaded regions in Panels (A), (C), and (E) indicate the minimum total constant dosage of exogenous estrogen and/or progesterone over 28 days that lowers maximum P4 concentration to 4.99 ng/mL. The shaded region below u1 (area under the curve or AUC) in Panel (B) is the total nonconstant dosage of exogenous E2 which suppresses the P4 level to 4.43 ng/mL, a reduction by about 92% of the total dosage in (A). Panel (D) illustrates the total nonconstant dosage of exogenous P4 that reduces maximum P4 to 4.66 ng/mL, a reduction by about 43% of the total dosage in (C). Panel (F) shows the combined nonconstant doses of exogenous E2 and P4 that gives a maximum P4 level of 4.31 ng/mL. Credit: Gavina et al., 2023, PLOS Computational Biology, CC-BY 4.0 (creativecommons.org/licenses/by/4.0/)

A normal menstrual cycle involves multiple phases which are regulated by the endocrine system and influenced by levels of various hormones. The most contraceptive approaches, including pills, injectables and implants, involve the administration of exogenous oestrogen and/or progesterone to block ovulation.

In the new study by Brenda Lyn A. Gavina, PhD student, and her collaborators, researchers used data on hormone levels in 23 women aged 20 to 34 with normal menstrual cycles.  The team developed computational models depicting the interactions between various hormone levels as well as the impacts of exogenous hormones.

The model provided evidence that it is possible to reduce the total dose by 92% in oestrogen-only contraceptives, or the total dose by 43% in progesterone-only contraceptives, and still prevent ovulation. By combining oestrogen and progesterone, the doses of each hormone could be reduced even further. In addition, the model showed the importance of timing the hormones during the cycle, pointing toward ways that exogenous oestrogen and progesterone could be given during only certain phases of the menstrual cycle rather than at steady constant doses.

“These results may give clinicians insights into optimal dosing formulations and schedule of therapy that can suppress ovulation,” the authors say.

Source: EurekAlert!

Medical Students Retain Knowledge Better from Virtual Reality Lessons

A trial published in the International Journal of Gynecology & Obstetrics lends support to the idea that 3D virtual reality lessons can improve medical students’ retention of knowledge and understanding of complex topics in obstetrics and gynaecology.

For the study, 21 students took part in a 15-minute virtual reality learning environment (VRLE) experience on the stages of foetal development, while 20 students received a PowerPoint tutorial on the same topic, serving as a control.

While the students’ level of knowledge increased after both learning experiences, it was only retained in the VRLE group at one-week follow up. Questionnaires completed by participants reflected a high degree of satisfaction with the VRLE tool compared with the traditional tutorial.

“Virtual reality learning tools hold potential to enhance student learning and are very well received by students,” said corresponding author Fionnuala McAuliffe, MD, of University College Dublin National Maternity Hospital, in Ireland.

Source: Wiley

Dimming the Lights Could Help Reduce Gestational Diabetes Risk

Photo by Shvets Productions on Pexels

Researchers at Northwestern Medicine suggest that pregnant persons should dim the lights in their home and turn off or at least dim their screens (computer monitors and smartphones) a few hours before bedtime to reduce the risk of gestational diabetes mellitus.

In their study published in the American Journal of Obstetrics and Gynecology Maternal Fetal Medicine, women who developed gestational diabetes mellitus in the multi-site study had greater light exposure in the three hours before sleep onset. They did not differ in their light exposure during daytime or sleep or in their activity levels compared to those who did not develop it.

“Our study suggests that light exposure before bedtime may be an under-recognised yet easily modifiable risk factor of gestational diabetes,” said lead study author Dr Minjee, Northwestern Medicine neurologist.

While exposure to light at night before bedtime may be linked to impaired glucose regulation in non-pregnant adults, little is known about the effect of evening light exposure during pregnancy on the risk of developing gestational diabetes.

This is believed to be one of the first multi-site studies to examine light exposure before sleep on the risk of developing gestational diabetes, a serious health complication for mother and child.

‘Alarming’ global rise in gestational diabetes

Gestational diabetes is on the rise in the U.S. and globally. About 4.5% of first-time pregnant women with a baby born between 2011 and 2013 developed gestational diabetes, which has been increasing on average 3.4% per three-year period until 2019. In 2020, the rate of gestational diabetes was 7.8% of all births in the US.

“It’s alarming,” Kim said. “Gestational diabetes is known to increase obstetric complications, and the mother’s risk of diabetes, heart disease and dementia. The offspring also are more likely to have obesity and hypertension as they grow up.”

Data show that women who have gestational diabetes are nearly 10 times more likely to develop type 2 diabetes mellitus compared to those do not have glucose issues during pregnancy, Kim said.

Bright light exposure prior to sleep can come from bright indoor lighting and from device screens.

“We don’t think about the potential harm of keeping the environment bright from the moment we wake up until we go to bed,” Kim said. “But it should be pretty dim for several hours before we go to bed. We probably don’t need that much light for whatever we do routinely in the evening.”

Scientists don’t know which source of bright light causes the problem, but it might all add up, Kim said.

“Try to reduce whatever light is in your environment in those three hours before you go to bed,” Kim said. “It’s best not to use your computer or phone during this period. But if you have to use them, keep the screens as dim as possible,” Kim said, suggesting people use the night light option and turn off the blue light.

If pregnant persons develop gestational diabetes with the first pregnancy, they are more likely to have it with the next pregnancy.

Pre-sleep light exposure increases heart rate, with knock-on effects

Pre-sleep light exposure may affect glucose metabolism through sympathetic overactivity, meaning the heart rate goes up before bed when it should go down. “It seems there is inappropriate activation of the fight or flight response when it is time to rest,” Kim said.

Data shows the sympathetic overactivity may lead to cardiometabolic disease, which is a cluster of conditions including abdominal obesity, insulin resistance, increased blood pressure and an imbalance of lipids, all leading to cardiovascular disease.

The study of 741 women in their second trimester was conducted at eight clinical U.S. sites between 2011 and 2013. The participants’ light exposure was measured by an actigraph worn on their wrists. The women were measured during the second trimester of pregnancy, the time when they receive routine screening for gestational diabetes.

After adjusting separately for age, BMI, race/ethnicity, education, commercial insurance, employment schedule, season, sleep duration, sleep midpoint, sleep regularity index, and daytime light exposure, pre-sleep light exposure remained significantly associated with gestational diabetes.

The growing rate of gestational diabetes has been partially attributed to increasing body mass index and the older age of pregnant persons.

“But even after adjusting for BMI and age, gestational diabetes is still rising,” Kim said. “We have a lot to prove, but my personal worry is that light may be silently contributing to this problem without most people realising the potential harm.”

Losing body weight and exercising also reduce the risk of developing gestational diabetes, which are important but take some effort.

Turning down lights is an easy fix

“Turning down the lights is an easy modification you can make,” Kim said.

“Now I’m the light police at home,” Kim said. “I see all this light I never thought about before. I try to dim the light as much as possible. Just for evening activities such as dinner and bathing the kids, you don’t need bright light.”

“This study highlights the importance of reducing light exposure in the hours before bedtime” said senior author Kathryn Reid, research professor of neurology at Feinberg.

Source: Northwestern University