Category: Obstetrics & Gynaecology

Antibiotics Taken During Pregnancy May Reduce Preterm Births

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A study of almost 1000 pregnant women in Zimbabwe found that a daily dose of a commonly used, safe and inexpensive antibiotic may have led to fewer babies being born early. Among women living with HIV, those who received the antibiotic had larger babies who were less likely to be preterm.

One in four live-born infants worldwide is preterm (born at 37 weeks’ gestation or before), is small for gestational age, or has a low birth weight. The mortality rate for these small and vulnerable newborns is high, with prematurity now the leading cause of death among children younger than 5 years of age. Maternal infections and inflammation during pregnancy are linked to adverse birth outcomes, particularly for babies born to mothers living with HIV, who have a greater risk of being born too small or too soon. 

An international group of researchers, led by Professor Andrew Prendergast from Queen Mary University of London, and Bernard Chasekwa from the Zvitambo Institute for Maternal and Child Health Research in Zimbabwe, conducted the Cotrimoxazole for Mothers to Improve Birthweight in Infants (COMBI) randomised controlled trial, to examine whether prescribing pregnant women a daily dose of trimethoprim–sulfamethoxazole (a broad-spectrum antimicrobial agent with anti-inflammatory properties, widely used in sub-Saharan Africa) would result in heavier birth weights, decreased premature births, and better health outcomes for their babies.  

993 pregnant women were recruited from three antenatal clinics in Shurugwi, a district in central Zimbabwe, and received either 960 mg of the drug or a placebo daily. The participants received regular antenatal care during their pregnancies and data regarding their birth outcomes were recorded. 

The study, published in the New England Journal of Medicine, found that although birthweight did not differ significantly between the two groups, the trimethoprim–sulfamethoxazole group showed a 40% reduction in the proportion of preterm births, compared to the placebo group. Overall, 6.9% of mothers receiving the drug had babies born preterm, compared to 11.5% of mothers receiving the placebo, and no women receiving antibiotics had babies born prior to 28 weeks. For babies born to a small group of 131 women with HIV, the reduction in premature births was especially marked, with only 2% of births in the trimethoprim–sulfamethoxazole group preterm, as compared with 14% in the placebo group. Babies exposed to antibiotics during pregnancy also showed a 177 gram increase in their birth weight. 

Bernard Chasekwa, first author, said: “Our trial, conducted within routine antenatal care and enrolling women predominantly from rural areas, showed that trimethoprim-sulfamethoxazole did not improve birthweight, which was our main outcome. However, there was an intriguing suggestion that it may have improved the length of pregnancy and reduced the proportion of preterm births. We now need to repeat this trial in different settings around the world to see whether antibiotics during pregnancy can help reduce the risk of prematurity.”  

Source: Queen Mary University of London

Do Bevacizumab’s Ovarian Cancer Clinical Trial Results Hold up in the Real World?

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A real-world study based on information from an electronic health records–derived database reveals limited benefits of adding bevacizumab to first-line chemotherapy for patients with ovarian cancer, consistent with previous clinical trials. The findings are published by Wiley online in CANCER, a peer-reviewed journal of the American Cancer Society.

Bevacizumab is a monoclonal antibody against vascular endothelial growth factor A that acts to inhibit malignant cell growth and blood vessel formation. It’s approved as a treatment for various types of cancer. In clinical trials of patients with ovarian cancer, adding bevacizumab to first-line chemotherapy did not prolong overall survival compared with chemotherapy alone, but this treatment strategy did improve overall survival in analyses limited to patients with high-risk prognostic factors—such as those with advanced disease and those who had residual cancer present after surgery. A final long-term analysis did not find an overall survival benefit associated with bevacizumab in the full patient cohort.

To investigate whether these findings also hold true in real-world clinical practice, researchers examined the electronic health records of 1,752 patients with stage III or IV ovarian cancer who initiated chemotherapy with or without bevacizumab in 2017–2023 and were followed for a median time of 1.5 years.

Among patients with high-risk prognostic factors, the median time to next treatment was significantly longer for those receiving chemotherapy plus bevacizumab compared with those receiving chemotherapy alone: 13.6 versus 11.7 months. (Time to next treatment is used to assess the duration of clinical benefit by measuring the time between initiating a treatment and starting the next line of therapy). In these patients, there was also a trend towards longer median overall survival for the combination therapy: 31.1 versus 27.4 months. Among patients without high-risk prognostic factors, outcomes did not differ with the addition of bevacizumab. Benefits therefore seemed limited to special subpopulations, mirroring the findings from clinical trials.

“Our results were similar to results from clinical trials,” said lead author Linda R. Duska, MD, MPH, of the University of Virginia School of Medicine. “Our findings suggest that clinicians should consider a patient’s risk factors before using bevacizumab with first-line chemotherapy in the treatment of advanced ovarian cancer.”  

Source: Wiley

Does Hormone Therapy Improve Heart Health in Menopausal Women?

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Deciding whether to start hormone therapy during the menopause transition, the life phase that’s the bookend to puberty and when a woman’s menstrual cycle stops, is a hotly debated topic. While hormone therapy is recommended to manage bothersome symptoms like hot flashes and night sweats, Matthew Nudy, assistant professor of medicine at the Penn State College of Medicine, said there’s confusion about the long-term effects of hormone therapy, especially on cardiovascular health.

However, long-term use of oestrogen-based hormone therapies may have beneficial effects on heart health, according to a new study led by Nudy. A multi-institutional team analysed data from hormone therapy clinical trials that were part of the Women’s Health Initiative (WHI), a long-term national study focused on menopausal women, and found that oestrogen-based hormone therapy improved biomarkers associated with cardiovascular health over time. In particular, the study suggests that hormone therapy may lower levels of lipoprotein(a), a genetic risk factor associated with a higher risk of heart attack and stroke.

Their findings were published in the journal Obstetrics & Gynecology.

“The pendulum has been swinging back and forth as to whether hormone therapy is safe for menopausal women, especially from a cardiovascular disease perspective,” Nudy said. “More recently, we’re recognising that hormone therapy is safe in younger menopausal women within 10 years of menopause onset, who are generally healthy and who have no known cardiovascular disease.”

The hormonal changes that accompany menopause come with an increased risk of cardiovascular disease. The decline in the oestrogen can lead to changes in cholesterol, blood pressure and plaque buildup in blood vessels, which increase the risk of heart attack and stroke.

The research team was interested in understanding the long-term effect of hormone therapy on cardiovascular biomarkers, which hasn’t been evaluated over an extended period of time. Prior research in the field primarily looked at short-term effects.

Here, the team analysed biomarkers associated with cardiovascular health over a six-year period from a subset of women who had participated in an oral hormone therapy clinical trial that was part of the WHI. Post-menopausal participants aged 50 to 79 were randomly assigned to one of two groups, an oestrogen-only group and an oestrogen plus progesterone group. They provided blood samples at baseline and at the one-, three- and six-years marks. In total, they analysed samples from 2696 women, approximately 10% of the total trial participants.

The research team found that hormone therapy had a beneficial effect on most biomarkers in both the oestrogen-only and the oestrogen-plus-progesterone groups over time. Levels of LDL cholesterol, the so-called “bad” cholesterol, were reduced by approximately 11% while total cholesterol and insulin resistance decreased in both groups. HDL cholesterol, the so-called “good” cholesterol, increased by 13% and 7% for the oestrogen-only and oestrogen-and-progesterone groups, respectively.

However, triglycerides and coagulation factors, proteins in the blood that help form blood clots, increased.

The decrease in lipoprotein(a) concentration was more pronounced among participants with American Indian or Alaska Native ancestry or Asian or Pacific Islander ancestry, by 41% and 38%, respectively. The reason why was unclear, Nudy said.

More surprising to the research team, they said, levels of lipoprotein(a), a type of cholesterol molecule, decreased 15% and 20% in the oestrogen-only and the oestrogen-plus-progesterone groups, respectively. Unlike other types of cholesterol, which can be influenced by lifestyle and health factors such as diet and smoking, concentrations of lipoprotein(a) are thought to be determined primarily by genetics, Nudy explained. Patients with a high lipoprotein(a) concentration have an increased risk of heart attack and stroke, especially at a younger age. There’s also an increased risk of aortic stenosis, where calcium builds up on a heart valve.

“As a cardiologist, this finding is the most interesting aspect of this research,” Nudy said. “Currently, there are no medications approved by the Food and Drug Administration (FDA) to lower lipoprotein(a). Here, we essentially found that oral hormone therapy significantly reduced lipoprotein(a) concentrations over the long-term.”

Nudy noted that the oestrogen therapy the women received in the clinical trial was conjugated equine oestrogens, a commonly prescribed form of oral oestrogen therapy. Before being absorbed by the body, oral hormone therapy is processed in the liver, through a process called first-pass metabolism. That process could increase inflammatory markers, which may explain the rise in triglycerides and coagulation factors.

“There are now other common formulations of oestrogen hormone therapy like transdermal oestrogen, which is administered through the skin,” Nudy said. “Newer studies have found that transdermal oestrogen doesn’t increase triglycerides, coagulation factors or inflammatory markers.”

For those considering menopause hormone therapy, Nudy recommended undergoing a cardiovascular disease risk assessment, even if the person hasn’t had a previous heart attack or stroke or hasn’t been diagnosed with cardiovascular disease. It will give health care providers more information when considering the best option to treat menopause symptoms.

“Currently, hormone therapy is not FDA-approved to reduce the risk of coronary artery disease or stroke,” Nudy said. 

Source: Penn State

Does Anaemia During Pregnancy Affect Newborns’ Risk of Heart Defects?

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New research published in BJOG: An International Journal of Obstetrics & Gynaecology found that mothers who are anaemic in early pregnancy face a higher likelihood of giving birth to a child with a heart defect.

The study assessed the health records of 2776 women with a child diagnosed with congenital heart disease who were matched to 13 880 women whose children did not have this condition.

Investigators found that 4.4% of children with congenital heart disease and 2.8% of children with normal heart function had anaemia. After adjusting for potential influencing factors, the odds of giving birth to a child with congenital heart disease was 47% higher among anaemic mothers.

“We already know that the risk of congenital heart disease can be raised by a variety of factors, but these results develop our understanding of anaemia specifically and take it from lab studies to the clinic. Knowing that early maternal anaemia is so damaging could be a gamechanger worldwide,” said corresponding author Duncan B. Sparrow, PhD, of the University of Oxford. “Because iron deficiency is the root cause of many cases of anaemia, widespread iron supplementation for women—both when trying for a baby and when pregnant—could help prevent congenital heart disease in many newborns before it has developed.”

Source: Wiley

Removing Ovaries and Fallopian Tubes Linked to Lower Risk of Early Death Among Certain Breast Cancer Patients

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Women diagnosed with breast cancer who carry particular BRCA1 and BRCA2 genetic variants are offered surgery to remove the ovaries and fallopian tubes as this dramatically reduces their risk of ovarian cancer. Now, Cambridge researchers have shown that this procedure – known as bilateral salpingo-oophorectomy (BSO) – is associated with a substantial reduction in the risk of early death among these women, without any serious side-effects.

Women with certain variants of the genes BRCA1 and BRCA2 have a high risk of developing ovarian and breast cancer. These women are recommended to have their ovaries and fallopian tubes removed at a relatively early age – between the ages 35 and 40 years for BRCA1 carriers, and between the ages 40 and 45 for BRCA2 carriers.

Previously, BSO has been shown to lead to an 80% reduction in the risk of developing ovarian cancer among these women, but there is concern that there may be unintended consequences as a result of the body’s main source of oestrogen being removed, which brings on early menopause. This can be especially challenging for BRCA1 and BRCA2 carriers with a history of breast cancer, as they may not typically receive hormone replacement therapy to manage symptoms. The overall impact of BSO in BRCA1 and BRCA2 carriers with a prior history of breast cancer remains uncertain. 

Ordinarily, researchers would assess the benefits and risks associated with BSO through randomised controlled trials, the ‘gold standard’ for testing how well treatments work. However, to do so in women who carry the BRCA1 and BRCA2 variants would be unethical as it would put them at substantially greater risk of developing ovarian cancer.

To work around this problem, a team at the University of Cambridge, in collaboration with the National Disease Registration Service (NDRS) in NHS England, turned to electronic health records and data from NHS genetic testing laboratories collected and curated by NDRS to examine the long-term outcomes of BSO among BRCA1 and BRCA2 PV carriers diagnosed with breast cancer. The results of their study, the first large-scale study of its kind, are published today in The Lancet Oncology.

The team identified a total of 3400 women carrying one of the BRCA1 and BRCA2 cancer-causing variants (around 1700 women for each variant). Around 850 of the BRCA1 carriers and 1,000 of the BRCA2 carriers had undergone BSO surgery.

Women who underwent BSO were around half as likely to die from cancer or any other cause over the follow-up period (a median follow-up time of 5.5 years). This reduction was more pronounced in BRCA2 carriers compared to BRCA1 carriers (a 56% reduction compared to 38% respectively). These women were also at around a 40% lower risk of developing a second cancer.

Although the team say it is impossible to say with 100% certainty that BSO causes this reduction in risk, they argue that the evidence points strongly towards this conclusion.

Importantly, the researchers found no link between BSO and increased risk of other long-term outcomes such as heart disease and stroke, or with depression. This is in contrast to previous studies that found evidence in the general population of an association between BSO and increased risk of these conditions.

First author Hend Hassan, a PhD student at the Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, and Wolfson College, Cambridge, said: “We know that removing the ovaries and fallopian tubes dramatically reduces the risk of ovarian cancer, but there’s been a question mark over the potential unintended consequences that might arise from the sudden onset of menopause that this causes.

“Reassuringly, our research has shown that for women with a personal history of breast cancer, this procedure brings clear benefits in terms of survival and a lower risk of other cancers without the adverse side effects such as heart conditions or depression.”

Most women undergoing BSO were white. Black and Asian women were around half as likely to have BSO compared to white women. Women who lived in less deprived areas were more likely to have BSO compared to those in the most-deprived category.

Hassan added: “Given the clear benefits that this procedure provides for at-risk women, it’s concerning that some groups of women are less likely to undergo it. We need to understand why this is and encourage uptake among these women.”

Professor Antonis Antoniou, from the Department of Public Health and Primary Care, the study’s senior author, said: “Our findings will be crucial for counselling women with cancer linked to one of the BRCA1 and BRCA2 variants, allowing them to make informed decisions about whether or not to opt for this operation.”

Professor Antoniou, who is also Director of the Cancer Data-Driven Detection programme, added: “The study also highlights the power of exceptional NHS datasets in driving impactful, clinically relevant research.”

The research was funded by Cancer Research UK, with additional support from the National Institute for Health and Care Research (NIHR) Cambridge Biomedical Research Centre.

The University of Cambridge is fundraising for a new hospital that will transform how we diagnose and treat cancer. Cambridge Cancer Research Hospital, a partnership with Cambridge University Hospitals NHS Foundation Trust, will treat patients across the East of England, but the research that takes place there promises to change the lives of cancer patients across the UK and beyond. Find out more here.

Reference

Hassan, H et al. Long-term health outcomes of bilateral salpingo-oophorectomy in BRCA1 and BRCA2 pathogenic variant carriers with personal history of breast cancer: a retrospective cohort study using linked electronic health records. Lancet Oncology; 7 May 2025; DOI: 10.1016/S1470-2045(25)00156-1

The original text of this story is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.

Read the original article.

Updated Review Raises Concern About Cannabis Use in Pregnancy

Research team finds moderate risk for preterm birth, low birth weight

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An updated systematic review finds that consuming cannabis while pregnant appears to increase the odds of preterm birth, low birth weight and infant death. This study by researchers at Oregon Health & Science University appears in JAMA Pediatrics.

Study lead author Jamie Lo, MD, MCR, is a physician-scientist who provides prenatal care for high-risk pregnancies at OHSU.

“Patients are coming to me in their prenatal visits saying, ‘I quit smoking and drinking, but is it safe to still use cannabis?’” said Lo, associate professor of obstetrics and gynaecology (maternal-foetal medicine) in the OHSU School of Medicine. “Until direct harms have been proven, they perceive it to be safe to use.”

In fact, cannabis remains one of the most common substances used in pregnancy that’s still illegal under federal law, and, unlike declines in prenatal use of alcohol or nicotine, cannabis use is continuing to increase. Lo said many of her patients are reluctant to give up cannabis during pregnancy because it helps to reduce common prenatal symptoms such as nausea, insomnia and pain.

Researchers updated the systematic review and meta-analysis, drawing on a total of 51 observational studies involving 21.1 million people to examine the potential adverse effects of cannabis use in pregnancy. The researchers found eight new studies since their previous update, raising the certainty of evidence from “very-low-to-low” to “moderate” for increased odds of low birth weight, preterm birth and babies being small for their gestational age.

The updated review also indicated increased odds of newborn mortality, though still with low certainty.

Researchers noted that the new systematic review includes a larger proportion of human observational studies examining people who only use cannabis, but don’t also use nicotine. And even though the evidence is low to moderate for adverse outcomes, Lo noted that the findings are consistent with definitive evidence in nonhuman primate models exposed to THC, the main psychoactive compound in cannabis.

The related research in animal models included standard prenatal ultrasound and MRI imaging that revealed a detrimental effect on the placenta, in terms of blood flow and availability of oxygen in addition to decreased volume of amniotic fluid.

“These findings tell me as an obstetrician that the placenta is not functioning as it normally would in pregnancy,” Lo said. “When the placenta isn’t functioning well, it can affect the baby’s development and growth.”

Even though cannabis remains a Schedule 1 substance under the federal Controlled Substances Act, Oregon is one of several states that have legalised it under state law for medicinal and recreational use. Lo said she recommends a harm-reduction approach to patients. For those who cannot abstain, she advises them to reduce the amount and frequency of use to help reduce the risk of prenatal and infant complications.

“Even using less can mitigate the risk,” she said. “Abstinence is ideal, but it’s not realistic for many patients.”

Source: Oregon Health & Science University

Gestational Diabetes Linked to ADHD in Children

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An Edith Cowan University (ECU) study has found children born to mothers who experienced gestational diabetes (GDM) during pregnancy are more likely to develop attention-deficient hyperactive disorder (ADHD) and externalising behaviour. The study appears in BMC Paediatrics.

The study used data from 200 000 mother-child pairs across Europe and Australia, and found that in children aged 7 to 10, those born to mothers with gestational diabetes had consistently higher ADHD symptoms.

Children aged 4 to 6 years, born to mothers with gestational diabetes consistently exhibited more externalising problems than those born who didn’t.

“Externalising symptoms are behaviours directed outward. Instead of experiencing depression or anxiety, these children often display hyperactivity, impulsivity, defiance, or aggression,” explained first author Dr Rachelle Pretorius, ECU Honorary researcher.

“Externalising problems frequently coexist with ADHD symptoms and tend to emerge before medical intervention, especially during the early school years,” she added.

“At younger ages, children may exhibit more externalising problems and as the child matures, symptoms or behaviour related to ADHD may become more apparent. ADHD does not have biological markers for diagnosis, making ADHD a disorder that is difficult to detect before symptoms manifest,” said senior author Professor Rae-Chi Huang.

It is still unclear why children exposed to gestational diabetes retained more externalising problems and ADHD symptoms respectively after adjustments.

“However, our findings suggest that these externalising behaviours may decrease over time but could extend into other domains such as neurodevelopment outcomes such as ADHD symptoms.”

Dr Pretorius noted that while the exact mechanics of gestational diabetes influence on child development is still unclear, it is believed that acute and chronic maternal inflammation during pregnancy may influence certain pathways in a child’s brain programming in-utero and contribute to neurodevelopment, cognitive and behaviour outcomes later in life.

“Several studies suggest that the severity of maternal diabetes, associated with maternal obesity, chronic inflammation have a joint impact on the development of autism spectrum disorder and ADHD in children, which is greater than the impact of either condition alone.”

Source: Edith Cowan University

Oestrogen and Progesterone Stimulate the Body to Make Opioids

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Female hormones can suppress pain by making immune cells near the spinal cord produce opioids, a new study from researchers at UC San Francisco has found. This stops pain signals before they get to the brain.

The discovery could help with developing new treatments for chronic pain. It may explain why some painkillers work better for women than men and why postmenopausal women, whose bodies produce less of the key hormones oestrogen and progesterone, experience more pain.

The work reveals an entirely new role for T regulatory immune cells (T-regs), which are known for their ability to reduce inflammation.

“The fact that there’s a sex-dependent influence on these cells – driven by oestrogen and progesterone – and that it’s not related at all to any immune function is very unusual,” said Elora Midavaine, PhD, a postdoctoral fellow and first author of the study, which appears in Science.

The researchers looked at T-regs in the protective layers that encase the brain and spinal cord in mice. Until now, scientists thought these tissue layers, called the meninges, only served to protect the central nervous system and eliminate waste. T-regs were only discovered there in recent years.

“What we are showing now is that the immune system actually uses the meninges to communicate with distant neurons that detect sensation on the skin,” said Sakeen Kashem, MD, PhD, an assistant professor of dermatology. “This is something we hadn’t known before.”

That communication begins when a neuron, often near the skin, receives a stimulus and sends a signal to the spinal cord.

The team found that the meninges surrounding the lower part of the spinal cord harbour an abundance of T-regs. To learn what their function was, the researchers knocked the cells out with a toxin.

The effect was striking: Without the T-regs, female mice became more sensitive to pain, while male mice did not. This sex-specific difference suggested that female mice rely more on T-regs to manage pain.

“It was both fascinating and puzzling,” said Kashem, who co-led the study with Allan Basbaum, PhD. “It actually made me sceptical initially.”

Further experiments revealed a relationship between T-regs and female hormones that no one had seen before: Estrogen and progesterone were prompting the cells to churn out enkephalin, a naturally occurring opioid.

Exactly how the hormones do this is a question the team hopes to answer in a future study. But even without that understanding, the awareness of this sex-dependent pathway is likely to lead to much-needed new approaches for treating pain.

In the short run, it may help physicians choose medications that could be more effective for a patient, depending on their sex. Certain migraine treatments, for example, are known to work better on women than men.

This could be particularly helpful for women who have gone through menopause and no longer produce oestrogen and progesterone, many of whom experience chronic pain.

The researchers have begun looking into the possibility of engineering T-regs to produce enkephalin on a constant basis in both men and women.

Source: University of California – San Francisco

Amniotic Fluid Protects Both Baby and Birthing Parent, Research Finds

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Researchers at Oregon Health & Science University have made new discoveries about amniotic fluid, which is historically not well understood in medical research due to the difficulty in obtaining it during pregnancy, especially across gestation in birthing parents.

In addition to providing much-needed cushion and protection for the foetus, amniotic fluid also aids in development of vital organs – especially the lungs, digestive tract and skin – and stabilises the temperature inside the womb.

The new study, published in the journal Research and Practice in Thrombosis and Haemostasis, found that the addition of amniotic fluid to plasma improves the blood’s ability to thicken and clot, which is a critical and likely a protective function throughout pregnancy and during delivery for both the birthing parent and the baby. It also appears to offer other unexpected functions, such as serving as a ‘pre-milk’ for foetuses.

The mechanism of amniotic fluid’s role in foetal development is not well understood and is understudied: The OHSU study is one of the first to identify how the features and properties of amniotic fluid change over time, especially those properties that play a role in thickening the blood, and how those changes can affect how maternal blood coagulates. If a pregnant person’s blood does not clot properly, it can create life-threatening complications for the foetus and birthing parent, including excessive bleeding during pregnancy and delivery.  

“We have always known that amniotic fluid is very important for foetal development and growth, but we don’t know much about it beyond that,” said the study’s corresponding author Jamie Lo, MD, MCR., associate professor of obstetrics and gynaecology (maternal-foetal medicine) in the OHSU School of Medicine, and Division of Reproductive & Developmental Sciences at the Oregon National Primate Research Center, or ONPRC. “We examined amniotic fluid across the pregnancy and found that indeed the composition and proteins in the amniotic fluid do change to match the growing needs of the developing baby.”

This discovery prompted Lo and her team to work with scientists in the Department of Biomedical Engineering at OHSU to take a deeper dive into the potential protective factors of amniotic fluid, and consider potential regenerative and therapeutic uses that could be developed down the road.

The research involved a multidisciplinary team including Lo, Chih Jen Yang, MD, Lyndsey Shorey-Kendrick, PhD, Joseph Shatzel, MD, MCR, Brian Scottoline, MD, PhD, and Owen McCarty, PhD.

Researchers analysed the properties of amniotic fluid obtained by amniocentesis, a prenatal test that involves sampling a small amount of amniotic fluid to examine the health of the pregnancy, from both human and non-human primates at gestational-age matched timepoints. The findings showed that amniotic fluid increases blood clotting through key fatty acids and proteins that change each trimester and help regulate coagulation.

With the untapped potential for amniotic fluid to aid in diagnosing and treating various prenatal conditions, researchers are now collaborating with Sanjay Malhotra, PhD, professor of cell, developmental and cancer biology in the OHSU School of Medicine, to target disorders of pregnancy – including disorders that affect the blood and blood-forming organs – that could benefit from the protective properties of proteins and other compounds within amniotic fluid.

Researchers are eager to learn more about the potential uses of amniotic fluid components and how they might be harnessed to improve prenatal and maternal health.

“Babies born prematurely miss out on critical weeks developing within amniotic fluid,” said the study’s co-senior author Brian Scottoline, MD, PhD, professor of paediatrics (neonatology), OHSU School of Medicine. “But if we have a better understanding of amniotic fluid, how it develops and what properties are valuable for what functions, that opens up many new possibilities for creating new therapies.”

“Through our research, our team is learning that amniotic fluid may be a critical precursor to breast milk – almost like ‘pre-term’ milk for a foetus in utero. With that analogy, could we eventually develop a formula that’s fit for preterm babies that mimics amniotic fluid, aiding in growth and development and protecting babies from complications of being born prematurely?” Lo added. “This is really the tip of the iceberg for what’s possible.”

Source: Oregon Health & Science University

Oxytocin Can ‘Pause’ Pregnancy After Conception

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Oxytocin, a hormone already known for its role in childbirth, milk release, and mother–infant bonding, may have a newfound purpose in mammalian reproduction. In times of maternal stress, the hormone can delay an embryo’s development for days to weeks after conception, a new study in rodents shows. According to the authors, the findings about so-called “diapause” may offer new insights into pregnancy and fertility issues faced by humans.

Led by researchers at NYU Langone Health, the study explored diapause, in which an embryo temporarily stops growing early in its development before it attaches to the lining of its mother’s uterus, a key step leading to the formation of the placenta. Known to occur in species as varied as armadillos, giant pandas, and seals, diapause is thought to have evolved to help expectant mothers preserve scarce resources (e.g., breast milk) by delaying birth until they have enough to successfully take care of their offspring.

Although recent studies have uncovered evidence that a form of diapause may occur in humans, the underlying mechanisms behind it have until now remained unclear.

The findings in mice showed that one type of stress that may cause diapause is milk production and release (lactation), as it requires a mother to expend bodily resources nursing already-born pups, and supplying nutrients to pups growing in the womb, at the same time. The study revealed that the time between conception and birth, typically 20 days for these animals, was delayed by about a week in pregnant rodents that were already nursing a litter.

Further, the research team showed that this delay was brought about by a rise in the production of oxytocin, levels of which are known to go up as a mother lactates. To confirm this role for the hormone, the researchers exposed mouse embryos in the lab to a single dose (either 1 microgram or 10 micrograms) of oxytocin, and found that even these small amounts delayed their implantation in the uterus by as much as three days. The team found that the chemical did more than just pause pregnancy: oxytocin surges that were large enough to mimic the amounts and timing measured during nursing caused loss of pregnancy in the mice in nearly all cases.

“Our findings shed light on the role of oxytocin in diapause,” said study co-author Moses V. Chao, PhD, a professor at NYU Grossman School of Medicine. “Because of this newfound connection, it is possible that abnormalities in the production of this hormone could play roles in infertility, premature or delayed birth, and miscarriage.”

A report on the findings appears in Science Advances in a special issue focused on women’s health.

In another part of the study, the team searched for a mechanism that would allow embryos to react to an oxytocin surge. They found that the hormone can bind to special proteins called receptors on the surface of a layer of cells known as the trophectoderm, which surrounds the early embryo and eventually forms the placenta.

Notably, mouse embryos that were genetically altered to disable oxytocin receptors lived long enough to implant into their mother’s placenta at much lower rates than normal embryos. This suggests that the ability to respond to oxytocin spikes and therefore go into diapause is somehow important for the developing pups’ survival, says Dr. Chao, who plans to examine this protective function in more detail.

“Despite being extremely common, infertility and developmental issues that can arise during pregnancy remain poorly understood and can have a lasting, devastating impact on parents and their children,” said study senior author Robert Froemke, PhD, professor of genetics. “Having a deeper understanding of the factors that contribute to these problems may allow experts to better address them in the future.”

The researchers next plan to examine how cell growth gets turned back on after diapause, Dr Froemke says. In addition, the team plans to explore how diapause may affect offsprings’ health and development after birth, and determine whether and how their discoveries can inform reproductive medicine.

Dr Froemke cautions that while the study results are promising, mice and humans have significant differences in their reproductive processes, despite both being mammals. He adds that the current investigation did not assess the role that other pregnancy-related hormones, such as oestrogen and progesterone, may play in diapause.

Source: NYU Langone Health / NYU Grossman School of Medicine