Category: Obstetrics & Gynaecology

Pregnant Women Over 4 Times as Likely to Use Cannabis if it is Legal

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US scientists conducting a nationwide study found that pregnant women living in states where cannabis is legally available are far more likely to use the substance, prompting a call for pregnant women to be screened for the drug.

Published in The American Journal of Drug and Alcohol Abuse, the findings show that pregnant women were around 4.6 times more likely to report using cannabis in states where it is legal for medical and recreational purposes, compared to where only CBD oil is allowed.

A large proportion of women reported using the drug for medical purposes, which is in keeping with “a growing body of evidence” that suggests in order to alleviate pregnancy symptoms cannabis is being used as a substitute for medical drugs in legalised areas.

“Therefore it is increasingly important to evaluate the risk-benefit profile of cannabis as compared to other medical treatments to understand any potential therapeutic indications for cannabis use in pregnancy,” says lead author Kathak Vachhani.

The team is calling for prenatal and primary care providers to screen and counsel patients regarding cannabis use in pregnancy, particularly in states where it is legal, for the potential effects on foetal development.

They also state public messaging “around the risks” of cannabis in pregnancy is “particularly relevant now,” as many states have recently implemented cannabis laws and established cannabis markets.

The legalisation of cannabis products has increased exponentially in the last decade in the United States. The legalisation has been piecemeal, as some states allow CBD oil, or marijuana for medical or recreational purposes. Use of these products has risen among all demographics.

Among the least studied are pregnant women. Because cannabis has been known to be used to treat some symptoms associated with pregnancy—notably nausea and vomiting.

Here, the team used data from the Behavioral Risk Factor Surveillance System compiled by the Centers for Disease Control and Prevention (CDC) between 2017 to 2020 to analyse the consumption of cannabis by 1,992 pregnant women.

While previous studies have examined the use of cannabis by pregnant women in restricted geographic areas and under particular legislative parameters, this study used a broader dataset to compare use across legalisation frameworks in 27 states.

Self-reported use was found to be “significantly higher” in pregnant women residing in states that allow medical and adult use, compared to those residing in states with restricted use.

“The unweighted dataset consisted of 426 CBD-only, 1114 medical, and 394 reactional group respondents,” the authors wrote claim. Weights were applied to each datapoint to obtain the population they represented. Of this weighted data, 2.4% from CBD-only regions reported cannabis use, while 7.1% from medical regions and 6.9% from adult-use regions reported the same. Respondents from the medical and recreational areas were 4.5 and 4.7 times more likely to use cannabis than those in CBD-only areas.

Most respondents who reported cannabis use smoked it partially or mostly for recreational purposes. “Mode of intake and reason for consumption did not differ between state groups,” the authors observe.

But what impact is this having on the mother or the foetus?

Previous studies have shown that medical cannabis usage during pregnancy can be effective for nausea and vomiting. Medical cannabis may be suitable to treat pregnancy-specific conditions which, if untreated, could be more harmful to the foetus than cannabis.

However, safe usage depends on having a comprehensive understanding of the benefits and risks of cannabis when weighed against the risks of untreated or refractory conditions such as hyperemesis gravidarum.

Therefore, more research is needed, states Vachhani, who is also from the University of Toronto Temerty Faculty of Medicine.

“Cannabis is a complex substance and its use is further complicated by factors such as the form of intake and frequency of use.

“From the mother’s health standpoint, our current understanding is rudimentary regarding the complex interplay between use (whether CBD or THC-based) and long-term health outcomes for the mother.

“There is currently no accepted therapeutic indication or safe amount of cannabis that may be consumed during pregnancy.

“Although further studies may lead to an accepted therapeutic indication, based on the current consensus the positive association between cannabis use and legalisation found in our study warrants further inquiry.”

The analysis carried out here was limited by a relatively small sample size, a lack of information regarding timing of use in pregnancy, lack of information about the chemical composition of cannabis consumed, and the potential for self-reporting biases.

Source: Taylor & Francis

A New Hormone-free Contraceptive Reinforces the Cervical Barrier

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A new non-hormonal contraceptive may be possible with a prophylactic gel made from naturally occurring ingredients, according to researchers writing in Science Translation Medicine. The gel reinforces the cervical mucus barrier, offering the first viable alternative to spermicides and contraception pills.

In tests on ovulating female sheep, the gel resulted in a 98% average decrease in uterine sperm numbers, compared to control animals. Birth control pills are recognised to be between 91 and 99% effective.

Only one of the eight sheep tested was found to have two sperm detected in its uterus after being treated with the topical gel. Thomas Crouzier, a biopolymers researcher at KTH, says the results demonstrate the potential of an unprecedented approach to preventing unwanted pregnancies by blocking sperm by engineering mucus rather than killing sperm cells as spermicides do.

Crouzier says that mechanism taps into cervical mucus’ natural capacity as a barrier that isolates the vagina, where bacteria proliferate, from the uterus and upper reproductive tract. Cervical mucus also regulates the movement of sperm. Leading up to ovulation the mucus barrier becomes a more selective gatekeeper, making exceptions for the passage of select sperm into the uterus.

The researchers change this dynamic by crosslinking molecules of mucin (the proteins that give mucus its lubricating property) with chitosan, a fibrous natural substance commonly used in medical materials such as hydrogels, meshes and sutures. This combination temporarily thickens cervical mucus so that sperm have more difficulty getting through.

The chitosan was shown to have a similar effect in lab tests using human cervical mucus and sperm. It reinforced the mucus barrier quickly, with a reduction in sperm penetration after one minute of exposure and full sperm blockage after five minutes.

Citing studies, Crouzier says that about 50% of women consider it important that their contraceptives do not contain hormones. “This new mechanism of action has the potential to be very effective, since it is reinforcing a barrier that already exists in the women’s reproductive tract,” he says.

“Vaginal gels like this can be applied in seconds,” Crouzier says. “We imagine that a product like this should be usable from seconds to a few hours before sexual intercourse. The effect could last for hours, but diminish over time as the mucus barrier is replaced naturally.”

Source: KTH Royal Institute of Technology

Oestrogen may Protect against Delirium in Older Women with UTIs

Photo by Karolina Grabowska

Delirium is common among women with urinary tract infections (UTIs) – especially those who have experienced menopause. In mouse models, researchers have been able to prevent symptoms of the condition by administering oestrogen. Their study was published in the peer-reviewed journal Scientific Reports.

“There has been a resurgence of interest in hormone replacement therapy, and this study, which builds on our previous work, shows that it may be a tool to mitigate delirium,” said Shouri Lahiri, MD, director of the Neurosciences Critical Care Unit and Neurocritical Care Research at Cedars-Sinai and senior author of the study. “I think it is a major step toward a clinical trial of oestrogen in human patients with UTIs.”

Lahiri said that delirium is a common problem in older women with UTIs.

“Even as a medical student, you know that if an older woman comes to the hospital and she’s confused, one of the first things you check is whether the patient has a UTI,” Lahiri said.

In previous studies, Lahiri’s team found a connection between delirium and an immune-regulating protein called interleukin 6 (IL-6). Events such as lung injury or UTI cause IL-6 to travel through the blood to the brain, causing symptoms such as disorientation and confusion. Oestrogen is a known suppressor of IL-6, so the investigators designed experiments to test its effects on UTI-induced delirium.

The researchers compared pre- and postmenopausal mice with UTIs and observed their behaviour in several types of specialised environments. They found that the mice in which menopause had been induced exhibited symptoms of delirium, such as anxiousness and confusion, while the others did not.

When they treated the mice with oestrogen, levels of IL-6 in the blood and delirium-like behaviour were greatly reduced. The behavioural differences were not related to UTI severity, as bacterial levels in the urine weren’t markedly different between the two groups, Lahiri said.

The investigators also looked at the direct effects of oestrogen on neurons, using what Lahiri called a “UTI in a dish.”

“We exposed individual neurons to an IL-6 inflammation cocktail to create UTI-like injury,” Lahiri said. “But when we added oestrogen to the cocktail, it mitigated the injury. So, we showed that there are at least two ways that oestrogen helps reduce symptoms of delirium. It reduces IL-6 levels in the blood and protects the neurons directly.”

Just how oestrogen acts to protect neurons is still unexplained. And before conducting a clinical trial, researchers need to identify which patients with UTIs are most likely to experience delirium and at what point oestrogen treatment might be most effective.

“Currently, it is common practice to treat UTI-induced delirium using antibiotics, even though there are no clinical trials that indicate this practice is effective and it is not supported by clinical practice guidelines,” said Nancy Sicotte, MD, chair of the Department of Neurology and the Women’s Guild Distinguished Chair in Neurology at Cedars-Sinai. “This work is an important step in determining whether modulating immune response via oestrogen replacement or other means is a more effective treatment.”

The team is also working to understand the different effects of delirium on females versus males, which was not a topic of this study. Effective treatment of delirium could be of long-term importance, Lahiri said, because it is a known risk factor for long-term cognitive impairments, such as Alzheimer’s disease and related dementia.

Source: Cedars-Sinai Medical Center

Even in Low-income Countries, ARVs Stop Maternal HIV Transmission

Pregnant with ultrasound image
Source: Pixabay

Antiretroviral drugs almost completely reduce the risk of mothers passing on HIV infection to their children, even in a low-income country with a high HIV incidence such as Tanzania, according to a new study in The Lancet HIV.

UNAIDS estimates that 11% of children born to HIV-positive mothers in Tanzania are infected with HIV, during childbirth or via breast milk. But the new study suggests this figure is actually much lower.

The researchers, from Karolinska Institutet in Sweden, examined more than 13 000 HIV-positive, pregnant women, at several health centres in one of Africa’s largest cities, Dar es Salaam, in Tanzania. The women were offered antiviral treatment through maternity care between 2015 and 2017.

Only 159 infants were infected 

The women were followed for 18 months after giving birth when most of them had stopped breastfeeding. When the researchers examined the mothers’ children, they discovered that only 159 of the more than 13 000 infants had been infected with HIV by the age of 1.5 years, translating to a risk of 1.4%, taking into account a margin of error.

The risk of infection was more than twice as high among women who sought care late in pregnancy or had advanced HIV. Conversely, the risk of infection was only 0.9% in those who had already received HIV treatment when they became pregnant. 

“HIV transmission from mother to child can in principle be stopped completely with modern antiviral drugs. But so far it has not been demonstrated in low-income countries in Africa with a high incidence of HIV infection,” says Goodluck Willey Lyatuu, physician and postdoctoral researcher, also at the Department of Global Public Health at Karolinska Institutet and first author of the study.

Early diagnostics are important 

The study is limited by challenges that may be typical in low-resource health systems, such as incomplete follow-up and missing data, and that risk factors such as stigma linked to HIV are rarely or never routinely investigated.

“But it is one of the largest cohort studies published from Africa on the risk of HIV transmission from mother to child where the baby is followed until the end of the breastfeeding period,” says says Anna Mia Ekström, clinical professor of global infectious disease epidemiology with a focus on HIV at the Department of Global Public Health at Karolinska Institutet and corresponding author of the study.

Source: Karolinksa Institutet

Lasting Postpartum Mental Health Problems may be Tied to Immune Response

Woman holding her chest
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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