Category: Obstetrics & Gynaecology

Categories : Diseases, Syndromes and Conditions Obstetrics & GynaecologyTags :

Clear Link between Autoimmune Disease and Perinatal Depression

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This is a pseudo-colored image of high-resolution gradient-echo MRI scan of a fixed cerebral hemisphere from a person with multiple sclerosis. Credit: Govind Bhagavatheeshwaran, Daniel Reich, National Institute of Neurological Disorders and Stroke, National Institutes of Health

Women with autoimmune disease are more likely to suffer from depression during pregnancy and after childbirth; conversely, women with a history of perinatal depression are at higher risk of developing autoimmune disease, according to a new study from Karolinska Institutet which is published in the journal Molecular Psychiatry.

Some of the most common autoimmune diseases are gluten intolerance (coeliac disease), autoimmune thyroiditis, rheumatoid arthritis, type 1 diabetes, and multiple sclerosis (MS). 

In the present study, researchers used data from the Swedish Medical Birth Register and identified all women who had given birth in Sweden between 2001 and 2013. Out of the resulting group of approximately 815 000 women and 1.3 million pregnancies, just over 55 000 women had been diagnosed with depression during their pregnancy or within a year after delivery. 

The researchers then compared the incidence of 41 autoimmune diseases in women with and without perinatal depression, controlling for familial factors such as genes and childhood environment by also including the affected women’s sisters.

Strongest association for MS

The results reveal a bidirectional association between perinatal depression and autoimmune thyroiditis, psoriasis, MS, ulcerative colitis, and coeliac disease. Overall, women with autoimmune disease were 30 per cent more likely to suffer perinatal depression. Conversely, women with perinatal depression were 30 per cent more likely to develop a subsequent autoimmune disease.

The association was strongest for the neurological disease MS, for which the risk was double in both directions. It was also strongest in women who had not had a previous psychiatric diagnosis.

“Our study suggests that there’s an immunological mechanism behind perinatal depression and that autoimmune diseases should be seen as a risk factor for this kind of depression,” says the study’s first author Emma Bränn, researcher at the Institute of Environmental Medicine at Karolinska Institutet.

Can have serious consequences

The researchers will now continue to examine the long-term effects of depression during pregnancy and in the first year following childbirth.

“Depression during this sensitive period can have serious consequences for both the mother and the baby,” says Dr Bränn. “We hope that our results will help decision-makers to steer funding towards maternal healthcare so that more women can get help and support in time.”

Since this was an observational study, no conclusions on causality can be drawn.

The study was financed by Karolinska Institutet, Forte (the Swedish Research Council for Health, Working Life and Welfare), the Swedish Research Councill and the Icelandic Research Fund. The researchers report no conflicts of interest.

Source: Karolinska Institutet

Categories : Mental Health Obstetrics & GynaecologyTags :

Perinatal Depression Triples the Risk of Suicidal Behaviour

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Photo by Sydney Sims on Unsplash

Maternal suicide is an alarming public health issue and the second most common cause of death during the postnatal period. New research from Karolinka Institutet in Sweden shows that mothers with clinically diagnosed perinatal depression had a three times higher risk of suicidal behaviour compared to mothers without perinatal depression. The findings were published in JAMA Network Open.

Some 13–36% of maternal deaths are attributable to suicide, and the consequences are devastating to the newborn and the family. Maternal suicide is linked to a complex interplay of risk factors, including history of psychiatric disorders, socioeconomic disparities, and inadequate access to healthcare service. It is of paramount importance to identify high-risk populations for preventing maternal suicide and suicidal attempt.

Our findings suggest that women with clinically diagnosed PND are at an increased risk of suicidal behavior, particularly within one year after PND yet throughout 18 years of follow-up. This highlights the pressing need for vigilant clinically monitoring and prompt intervention for this vulnerable population to prevent such devastating outcomes, regardless of pre-pregnancy history of psychiatric disorders.

Hang Yu, PhD student

In this nationwide population-matched cohort study with a maximal follow-up of 18 years, 86 551 women with PND from 2001 to 2017 and 865 510 unaffected women individually matched on age and calendar year at delivery. Sibling comparison was employed to account for familial confounding. It was found that women with a clinical diagnosis of PND have an elevated risk of suicidal behaviour compared to population-matched women or their full sisters without PND. Attenuated yet still substantially elevated risks were observed when comparing with full sisters without PND who share partial genetic and familial environmental factors with affected women. Importantly, such excess risk was apparent among women regardless of their history of psychiatric disorders, suggesting that PND is linked to an added risk of suicidal behaviour beyond that the risk associated with psychiatric disorders occurring before the perinatal period. Moreover, the risk elevations were particularly high shortly after the PND diagnosis, and despite of the rapid decline over time, remained throughout 18 years of follow-up.

Source: Karolinska Institutet

Categories : General Interest Obstetrics & GynaecologyTags :

Gauteng Health Rings in the New Year with 112 Births

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Photo by Christian Bowen on Unsplash

New Year’s Day saw the Gauteng Department of Health welcoming 112 babies into the world, the lion’s share of more than 400 births in total for the country. According to data released by Gauteng Health on X/Twitter, in the province’s public healthcare facilities, there were a total of 59 boys and 53 girls. Thelle Mogoerane Regional Hospital topped the table with 10 babies, followed by Chris Hani Baragwanath Academic Hospital (CHBAH) with 9 babies. But all of this was relatively quiet compared to Christmas Day, which saw more than three times the New Years’ Day number.

MEC Nkomo Nomantu together with MMC for Health Rina Marx joined the postpartum mothers at Dr George Mukhari Academic Hospital on the morning of New Year’s Day in welcoming their new arrivals. Gauteng’s academic hospitals recorded 19 births, while there were 10 births at the tertiary hospitals. Regional and district hospitals had 69 births and community healthcare centres had 14.

Christmas Day saw 387 babies born, 201 of them girls and 186 boys. CHBAH welcomed the most, with 46 births, followed by Tembisa Hospital with 38.

Categories : Obstetrics & GynaecologyTags :

Cause of Pregnancy Sickness – and Potential Treatment

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Photo by Anna Hecker on Unsplash

A Cambridge-led study has shown why many women experience nausea and vomiting during pregnancy – and why some women, including the Duchess of Cambridge, become so sick they need to be admitted to hospital.

The culprit is a hormone produced by the foetus – a protein known as GDF15. But how sick the mother feels depends on a combination of how much of the hormone is produced by the foetus

The discovery, published today in Nature, points to a potential way to prevent pregnancy sickness by exposing mothers to GDF15 ahead of pregnancy to build up their resilience.

As many as seven in ten pregnancies are affected by nausea and vomiting. In some women – thought to be between one and three in 100 pregnancies – it can be severe, even threatening the life of the foetus and the mother and requiring intravenous fluid replacement to prevent dangerous levels of dehydration. So-called hyperemesis gravidarum is the commonest cause of admission to hospital of women in the first three months of pregnancy.

Although some therapies exist to treat pregnancy sickness and are at least partially effective, widespread ignorance of the disorder compounded by fear of using medication in pregnancy mean that many women with this condition are inadequately treated.

Until recently, the cause of pregnancy sickness was entirely unknown. Recently, some evidence, from biochemical and genetic studies has suggested that it might relate to the production by the placenta of the hormone GDF15, which acts on the mother’s brain to cause her to feel nauseous and vomit.

Now, an international study, involving scientists at the University of Cambridge and researchers in Scotland, the USA and Sri Lanka, has made a major advance in understanding the role of GDF15 in pregnancy sickness, including hyperemesis gravidarum.

The team studied data from women recruited to a number of studies, including at the Rosie Maternity Hospital, part of Cambridge University Hospitals NHS Foundation Trust and Peterborough City Hospital, North West Anglia NHS Foundation Trust. They used a combination of approaches including human genetics, new ways of measuring hormones in pregnant women’s blood, and studies in cells and mice.

The researchers showed that the degree of nausea and vomiting that a woman experiences in pregnancy is directly related to both the amount of GDF15 made by the foetal part of placenta and sent into her bloodstream, and how sensitive she is to the nauseating effect of this hormone.

GDF15 is made at low levels in all tissues outside of pregnancy. How sensitive the mother is to the hormone during pregnancy is influenced by how much of it she was exposed to prior to pregnancy – women with normally low levels of GDF15 in blood have a higher risk of developing severe nausea and vomiting in pregnancy..

The team found that a rare genetic variant that puts women at a much greater risk of hyperemesis gravidarum was associated with lower levels of the hormone in the blood and tissues outside of pregnancy. Similarly, women with the inherited blood disorder beta thalassemia, which causes them to have naturally very high levels of GDF15 prior to pregnancy, experience little or no nausea or vomiting.

Professor Sir Stephen O’Rahilly, Co-Director of the Wellcome-Medical Research Council Institute of Metabolic Science at the University of Cambridge, who led the collaboration, said: “Most women who become pregnant will experience nausea and sickness at some point, and while this is not pleasant, for some women it can be much worse – they’ll become so sick they require treatment and even hospitalisation.

“We now know why: the baby growing in the womb is producing a hormone at levels the mother is not used to. The more sensitive she is to this hormone, the sicker she will become. Knowing this gives us a clue as to how we might prevent this from happening. It also makes us more confident that preventing GDF15 from accessing its highly specific receptor in the mother’s brain will ultimately form the basis for an effective and safe way of treating this disorder.”

Mice exposed to acute, high levels of GDF15 showed signs of loss of appetite, suggesting that they were experiencing nausea, but mice treated with a long-acting form of GDF15 did not show similar behaviour when exposed to acute levels of the hormone. The researchers believe that building up woman’s tolerance to the hormone prior to pregnancy could hold the key to preventing sickness.

Co-author Dr Marlena Fejzo from the Department of Population and Public Health Sciences at the University of Southern California whose team had previously identified the genetic association between GDF15 and hyperemesis gravidarum, has first-hand experience with the condition. “When I was pregnant, I became so ill that I could barely move without being sick. When I tried to find out why, I realised how little was known about my condition, despite pregnancy nausea being very common.

“Hopefully, now that we understand the cause of hyperemesis gravidarum, we’re a step closer to developing effective treatments to stop other mothers going through what I and many other women have experienced.”

The work involved collaboration between scientists at the University of Cambridge, University of Southern California, University of Edinburgh, University of Glasgow and Kelaniya University, Colombo, Sri Lanka. The principal UK funders of the study were the Medical Research Council and Wellcome, with support from the National Institute for Health and Care Research Cambridge Biomedical Research Centre.

The original text of this story is licensed under a Creative Commons License. 

Source: University of Cambridge

Categories : Metabolic Disorders Obstetrics & GynaecologyTags :

Newer Diabetes Drugs don’t Increase Risk to Foetus

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Newer diabetes medicines do not appear to increase the risk of birth defects. The largest comparative study to date found no increased risk compared to treatment with insulin, which is considered safe during pregnancy. The study was published in JAMA Internal Medicine.

Newer diabetes drugs such as sulfonylureas, DPP-4 inhibitors, GLP-1 receptor agonists and SGLT2 inhibitors are being increasingly used, both in the treatment of diabetes, but also extended indications for several of the preparations. 

However, knowledge of the foetal effects of these drugs is still low, so women with type 2 diabetes are often advised to switch to insulin before a planned pregnancy because it is considered safe. However, not all pregnancies are planned and more and more people are becoming pregnant while being treated with these drugs.

An international research team has now investigated whether the use of these drugs during pregnancy increases the risk of birth defects. The researchers used health data from 3.5 million pregnancies in six different countries (Sweden, Norway, Finland, Iceland, USA and Israel) between 2009 and 2021. Among these 3.5 million women, nearly 52 000 were diagnosed with type 2 diabetes and more than 8000 took one of the newer diabetes drugs in the three months before or after their last menstrual period.

Diabetes itself poses a risk of birth defects. High blood sugar levels in early pregnancy, which are more common in people with diabetes, increase the risk of foetal malformations. Therefore, the researchers were not surprised to see a slightly elevated risk in this group.

Among women diagnosed with type 2 diabetes before pregnancy, 5.3% of babies were born with severe birth defects, including 2.2% with heart defects, compared to the overall group where 3.8% had severe birth defects and 1.3% with heart defects. 

No increased risk of birth defects

However, the researchers found that the women with diabetes treated with the newer diabetes drugs did not have a higher risk of giving birth to children with birth defects than the women with diabetes treated with insulin.

“It has already been shown that insulin is safe to use during pregnancy and that it does not cross the placenta. The increased risk of birth defects in the children of women with type 2 diabetes using the newer diabetes drugs is therefore very likely caused by the disease,” says first author Carolyn Cesta, Associate Professor at the Center for Drug Epidemiology at Karolinska Institutet.

Despite being the largest study in this field to date, covering more than 3.5 million pregnancies, relatively few women used the new diabetes drugs, and the researchers stress that further studies are needed to confirm the results. However, they note that the study still shows that these drugs do not pose a major risk of birth defects.

As type 2 diabetes becomes more common among women of childbearing age and as GLP-1 receptor agonists such as semaglutide (Wegovy, Ozempic) are approved to treat obesity, the number of exposed pregnancies is likely to increase. 

“Our findings provide a first indication of the safety of infants exposed to these medications during pregnancy,” says Carolyn Cesta.

Source: Karolinska Institutet

Categories : Metabolic Disorders Obstetrics & GynaecologyTags :

Macrophages ‘Eat’ Pancreatic β Cells to Regulate Insulin Post Partum

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A 3D map of the islet density routes throughout the healthy human pancreas. Source: Wikimedia CC0

Scientists have long known that pancreatic β cells increase during pregnancy and promptly return to their original number following birth. But the underlying mechanisms that cause the cells to go back to their original number are still not well understood.

In a significant breakthrough, a research group using mouse models, has discovered that macrophages ‘eat’ (phagocytose) the pancreatic β cells, thereby revealing the process behind their return to previous levels after pregnancy.

The research group, which was led by Associate Professor Junta Imai, Assistant Professor Akira Endo, and Professor Hideki Katagiri from Tohoku University’s Graduate School of Medicine, published the results in the journal Development Cell.

Initially, the group examined the number of pancreatic β cells in the islets of Langerhans in a mouse model of pregnancy.

They confirmed the cell number was double at the end of the pregnancy when compared to non-pregnant mice, but that it then gradually decreased, returning to the original amount after delivery.

“After we observed the islets of Langerhans before and after delivery, we noticed an increase in macrophages, which protect the body from infections by engulfing bacteria, foreign substances and dead cells, after delivery,” says Imai.

“When we applied treatment to inhibit this process, the blood glucose levels became too low (hypoglycaemia).”

Additional microscopic observation of the islets of Langerhans after birth revealed β cells to be phagocytosed by macrophages.

This mechanism appeared to keep the mother’s blood glucose levels from decreasing excessively after delivery by rapidly reducing pancreatic β cells to their normal pre-pregnancy number.

Next, the group identified the protein responsible for attracting the macrophages into the islets of Langerhans: cytokine CXCL10.

Accordingly, the inhibition of CXCL10 function suppressed the decrease in pancreatic β cells after birth.

“We hope our results will contribute to clarifying the means by which normal blood glucose levels are maintained as well as the development of methods to prevent and treat diabetes,” adds Imai.

Source: Tohoku University

Categories : Cardiovascular Disease Obstetrics & GynaecologyTags :

Monitoring for Foetal Heart Condition in Pregnant Women with Autoimmune Antibodies

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Some individuals with anti-Ro/SSA antibodies (anti–Sjögren’s-syndrome–related antigen A autoantibodies, also called anti-Ro antibodies) have autoimmune diseases such as lupus or Sjögren’s syndrome, but many have no symptoms. A clinical trial published in Arthritis & Rheumatology found that high levels of these antibodies in pregnant women are associated with foetal atrioventricular block (AVB), which occurs when inflammation and subsequent scarring prevent electric signals from the heart’s atria from reaching the ventricles. The disease is associated with life-long pacing and can be fatal.

In the trial, called Surveillance To Prevent AV Block Likely to Occur Quickly (STOP BLOQ), the incidence of AVB increased with higher levels of anti-Ro/SSA antibodies, reaching 7.7% for those in the top quartile, which increased to 27.3% in those with a previous child who had AVB, although participant numbers in that category were small.  Antibody titres did not change over time. The trial also revealed that home-based foetal heart rate monitoring reliably detected conduction abnormalities, which may reduce the need for serial echocardiograms.

“Examining the levels of anti-Ro/SSA antibodies is an important advance since for women with low titres, monitoring is probably not necessary and for those with high titres the increased risk supports surveillance,” said corresponding author Jill Buyon, MD, of NYU Langone Health. She added that this study also indicated that titres of antibodies do not change and that additional factors besides antibodies contribute to risk.

“That home monitoring can rapidly and accurately identify early foetal conduction disease is a major step forward that may significantly decrease the need for echocardiograms and hopefully facilitate reversibility,” added senior author and research professor Bettina Cuneo MD, of the University of Arizona-Tucson College of Medicine.

Source: Wiley

Categories : Obstetrics & Gynaecology Substance UseTags :

Cannabis Use in Pregnancy Linked to Adverse Birth Outcomes

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A meta-analysis of studies published over the past 40 years on cannabis use during pregnancy has found an association between foetal exposure to cannabis in the womb and preterm delivery, low birth weight and the need for neonatal intensive care admission (NICU). The study was published today in the journal Addiction. 

Previous research has indicated that THC, the main psychoactive component in cannabis, can cross the placenta to the foetus during pregnancy and bind to receptors in the foetal brain.

The meta-analysis examined the results of 57 studies around the world that included almost 13 million infants in total.  Based on either self-reports from pregnant women, or blood and saliva testing depending on the study, just over 100 000 infants were found to be exposed to cannabis in the womb. While none of the studies found a direct causal relationship between cannabis use during pregnancy and adverse birth outcomes, the combined results indicated that newborns exposed to cannabis during pregnancy were twice as likely to require NICU admission, twice as likely to have a low birth rate and one and a half times more likely to be born early.

While there has been little research on cannabis use during pregnancy since cannabis was legalised in Canada five years ago, an American study has indicated an increase in cannabis use during pregnancy in states where it has been legalised and the perceived risk of harm from cannabis has decreased. The study states that overall cannabis use in pregnancy has doubled in the past 20 years, with approximately 10% of pregnancies associated with cannabis exposure. Some studies indicated it was being used to alleviate symptoms of nausea, poor appetite, insomnia or anxiety during pregnancy.

Canada’s Lower Risk Cannabis Use Guidelines, developed by a nationwide team led by CAMH scientists, recommends cannabis abstinence during pregnancy.

“This research emphasizes the importance of healthcare providers making an effort to create a safe space talking to pregnant women and women planning to be pregnant about their cannabis use and their motivations for using it to educate them about the potential risks and empower them to make informed decisions for their child,” says lead author Maryam Sorkhou, a PHD student within the addictions division at CAMH as well as the University of Toronto. Ms Sorkhou is overseen at CAMH by Senior Scientist and paper co-author Dr Tony George.

Source: Centre for Addiction and Mental Health

Categories : Obstetrics & Gynaecology PaediatricsTags :

Umbilical Cord Milking Safer for Preterm Babies Born after 28 Weeks

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A treatment to move blood from the umbilical cord into an infant’s body may provide a safe option for preterm infants born after 28 weeks who need rapid support, suggests a study supported by the National Institutes of Health. The procedure, called umbilical cord milking, involves gently squeezing the cord between the thumb and forefinger and pushing the blood into the newborn’s abdomen.

The new findings suggest that concerns raised by a 2019 study of infants born before 28 weeks (which concluded that umbilical cord milking might increase the risk of bleeding inside the brain) do not apply to preterm infants born after 28 weeks. The current study appears in Pediatrics.

The standard procedure, delaying cord clamping while blood naturally flows into the infant’s body, takes 30 to 180 seconds. However, cord milking, takes about 20 seconds, reducing delay for infants who need immediate assistance, such as respiratory support. Both procedures allow for umbilical cord blood to reach the infant’s body before clamping, reducing the risk of anaemia and other complications seen among infants receiving immediate cord clamping and cutting.

The study was conducted by Anup Katheria, M.D., of the Sharp Mary Birch Hospital for Women & Newborns in San Diego, and colleagues in the United States, Canada and Europe. It was supported by NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development.

More than 1000 infants were randomly assigned either to umbilical cord milking or delayed cord clamping. Rates of severe intraventricular haemorrhage and/or death did not differ significantly between the two groups (just over 1%). Moreover, the rates of overall intraventricular haemorrhage were also similar between the groups (approximately 12%). The researchers will follow all the infants in the study for two years to observe longer term outcomes.

Source: NIH/Eunice Kennedy Shriver National Institute of Child Health and Human Development

Categories : Obstetrics & GynaecologyTags : 1 Comment

Trial Shows Add-on NSAID Increases Success Rate of Morning-after Pill

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Research on adding a long-acting nonsteroidal anti-inflammatory drug (NSAID) to an oral emergency contraceptive pill (also known as the morning-after pill) showed that it increases the effectiveness of pregnancy prevention. The study findings were recently published in The Lancet.

Emergency contraception is a contraceptive method that can be used to prevent an unintended pregnancy when a regular contraceptive method fails or is not used. It can be in the form of an oral emergency contraceptive pill or the insertion of a copper intrauterine contraceptive device (Cu-IUD). The oral levonorgestrel emergency contraceptive pill is one of the most popular choices of emergency contraception and is widely used in most countries. It was pioneered by a clinical trial in Hong Kong led by HKUMed’s Professor Ho Pak-chung, published in 1993. However, all contraceptive methods have a failure rate. Hence, the research team is continuing its efforts to explore more effective options.

Prostaglandins mediate a number of biological processes, including inflammatory responses. In the reproductive system, prostaglandin is an important mediator of processes like ovulation, fertilisation and embryo implantation. The research team postulated that adding a medication that blocks prostaglandin synthesis may have an additional complementary effect in achieving contraception.

The collaborative research team, including members of LKS Faculty of Medicine of the University of Hong Kong (HKUMed), as well as The Family Planning Association of Hong Kong (FPAHK) and Sweden’s Karolinska Institutet, conducted the world’s first randomised, placebo-controlled trial on the use of piroxicam, an NSAID used to treat arthritis pain, which blocks prostaglandin production in the body, in combination with the levonorgestrel emergency contraceptive pill. The findings revealed that with the new combination regimen, only one out of 418 women became pregnant, while seven out of another 418 women receiving levonorgestrel and a placebo became pregnant. The results showed that the percentage of pregnancies prevented by piroxicam-levonorgestrel co-treatment (94.7%) was significantly higher than that of the levonorgestrel emergency contraceptive pill alone (63.4%). There was no significant difference in the occurrence of adverse effects, including changes to the menstrual bleeding pattern and stomach ache following intake of the two regimens.

Significance of the study

Chief-investigator Dr Raymond Li Hang-wun, from HKUMed, said, “Our study is the first to find that piroxicam, a readily available medication, taken at the same time as the levonorgestrel pill can prevent more pregnancies than levonorgestrel alone. We hope these findings will lead to further research and ultimately changes in clinical guidelines to enable women around the world to access more effective emergency contraception.”

Co-investigator Dr Sue Lo Seen-tsing, from FPAHK, said, “The levonorgestrel pill was registered in Hong Kong in 2002 and has been used safely since then. Locally, emergency contraceptives must be prescribed by healthcare providers, who assess which emergency contraceptive method is the most suitable in each case. Contraceptive counselling should be provided to help women seeking emergency contraception understand that it cannot replace regular contraceptives and to motivate them to use the latter. Since there is still a small failure rate, a follow-up visit is important. The levonorgestrel emergency contraception pill should be taken within 72 hours after unprotected sex; the earlier it is taken, the more effective it is.”

Source: The University of Hong Kong