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Doctors Caution Over Weight Loss Drug Link to Nurse’s Death
Doctors have urged caution in linking the weight loss drug tirzepatide to the death of a 58-year-old nurse from Scotland.
Susan McGowan, from North Lanarkshire, took two low-dose injections of tirzepatide (Mounjaro) over the course of about 2 weeks before her death in September.
BBC News reported that multiple organ failure, septic shock, and pancreatitis were listed on her death certificate as the immediate cause of death, with “the use of prescribed tirzepatide” recorded as a contributing factor.
McGowan worked as a nurse at University Hospital Monklands in Airdrie. A family member said that, apart from carrying a “bit of extra weight,” she had been otherwise healthy and was not taking any other medication.
It is understood that McGowan had sought medical advice before purchasing a prescription for tirzepatide through a registered UK pharmacy. However, days after administering a second injection, she went to A&E at Monklands with severe stomach pain and sickness. She died on September 4.
Expert Insights
Commenting to the Science Media Centre (SMC), Amanda Adler, MD, PhD, professor of diabetic medicine and health policy at the University of Oxford, described the nurse’s death as “sad” but said that “whether or not it was related to tirzepatide may be difficult to prove.” While tirzepatide can be associated with uncommon problems such as acute pancreatitis, “one can develop acute pancreatitis for many other reasons as well,” she said.
Naveed Sattar, MD, PhD, professor of metabolic medicine at the University of Glasgow, noted that data from multiple trials of tirzepatide, involving around 10,000 people living with diabetes or obesity, “do not suggest a higher risk of pancreatitis.” Furthermore, “the data seem to show acceptable safety thus far and a range of benefits including sizable average weight loss (near 20%), strong diabetes prevention, and considerable benefits in people living with sleep apnea,” he told the SMC.
Approved Based on Extensive Assessment
Tirzepatide, a GLP-1 receptor agonist, was approved for use as a weight loss aid in the United Kingdom in November last year by the Medicines and Healthcare products Regulatory Agency (MHRA). It lists nausea, diarrhea, and vomiting as the most common side effects, as well as hypoglycemia for patients with diabetes.
Available figures under the Yellow Card scheme up to 19 May 2024 show that there were 208 adverse drug reactions reported about tirzepatide this year, including 31 serious reactions and one suspected death of a man in his 60s.
In a statement, a spokesperson for the drug’s manufacturer, Eli Lilly, said, “Patient safety is Lilly’s top priority. We are committed to continually monitoring, evaluating, and reporting safety information for all Lilly medicines.
“Mounjaro (tirzepatide) was approved based on extensive assessment of the benefits and risks of the medicine, and we provide information about the benefits and risks of all our medicines to regulators around the world to ensure the latest information is available for prescribers. If anyone is experiencing side effects when taking any Lilly medicine, they should talk to their doctor or other healthcare professional.”
In October, the NHS submitted plans to the National Institute for Health and Care Excellence (NICE) for a phased rollout of tirzepatide in England that would initially prioritize patients with the greatest clinical need. The first phase would see the drug available to people with a body mass index of more than 40 kg/m2 who also suffer from at least three of the main weight-related health problems: hypertension, dyslipidemia, obstructive sleep apnea, and cardiovascular disease.
“Our sincere sympathies are with the family of individual concerned,” said Alison Cave, MHRA Chief Safety Officer.
“Patient safety is our top priority and no medicine would be approved unless it met our expected standards of safety, quality, and effectiveness. Our role is to continually monitor the safety of medicines during their use, such as GLP-1 RAs. We have robust, safety monitoring and surveillance systems in place for all healthcare products.
“New medicines, such as tirzepatide, are more intensively monitored to ensure that any new safety issues are identified promptly. We strongly encourage the reporting of all suspected reactions to newer medicines, which are denoted by an inverted Black Triangle symbol.
“On the basis of the current evidence the benefits of GLP-1 RAs outweigh the potential risks when used for the licensed indications. The decision to start, continue, or stop treatments should be made jointly by patients and their doctor, based on full consideration of the benefits and risks.”
She encouraged patients and healthcare professionals to continue reporting suspected side effects to GLP-1 RAs, such as tirzepatide, through the Yellow Card Scheme. “When a safety issue is confirmed, we always act promptly to inform patients and healthcare professionals and take appropriate steps to mitigate any identified risk.”
The Department of Health and Social Care declined to comment.
Adler disclosed being involved as an unpaid investigator on an Eli Lilly–funded trial for a different drug. Sattar has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Doctors have urged caution in linking the weight loss drug tirzepatide to the death of a 58-year-old nurse from Scotland.
Susan McGowan, from North Lanarkshire, took two low-dose injections of tirzepatide (Mounjaro) over the course of about 2 weeks before her death in September.
BBC News reported that multiple organ failure, septic shock, and pancreatitis were listed on her death certificate as the immediate cause of death, with “the use of prescribed tirzepatide” recorded as a contributing factor.
McGowan worked as a nurse at University Hospital Monklands in Airdrie. A family member said that, apart from carrying a “bit of extra weight,” she had been otherwise healthy and was not taking any other medication.
It is understood that McGowan had sought medical advice before purchasing a prescription for tirzepatide through a registered UK pharmacy. However, days after administering a second injection, she went to A&E at Monklands with severe stomach pain and sickness. She died on September 4.
Expert Insights
Commenting to the Science Media Centre (SMC), Amanda Adler, MD, PhD, professor of diabetic medicine and health policy at the University of Oxford, described the nurse’s death as “sad” but said that “whether or not it was related to tirzepatide may be difficult to prove.” While tirzepatide can be associated with uncommon problems such as acute pancreatitis, “one can develop acute pancreatitis for many other reasons as well,” she said.
Naveed Sattar, MD, PhD, professor of metabolic medicine at the University of Glasgow, noted that data from multiple trials of tirzepatide, involving around 10,000 people living with diabetes or obesity, “do not suggest a higher risk of pancreatitis.” Furthermore, “the data seem to show acceptable safety thus far and a range of benefits including sizable average weight loss (near 20%), strong diabetes prevention, and considerable benefits in people living with sleep apnea,” he told the SMC.
Approved Based on Extensive Assessment
Tirzepatide, a GLP-1 receptor agonist, was approved for use as a weight loss aid in the United Kingdom in November last year by the Medicines and Healthcare products Regulatory Agency (MHRA). It lists nausea, diarrhea, and vomiting as the most common side effects, as well as hypoglycemia for patients with diabetes.
Available figures under the Yellow Card scheme up to 19 May 2024 show that there were 208 adverse drug reactions reported about tirzepatide this year, including 31 serious reactions and one suspected death of a man in his 60s.
In a statement, a spokesperson for the drug’s manufacturer, Eli Lilly, said, “Patient safety is Lilly’s top priority. We are committed to continually monitoring, evaluating, and reporting safety information for all Lilly medicines.
“Mounjaro (tirzepatide) was approved based on extensive assessment of the benefits and risks of the medicine, and we provide information about the benefits and risks of all our medicines to regulators around the world to ensure the latest information is available for prescribers. If anyone is experiencing side effects when taking any Lilly medicine, they should talk to their doctor or other healthcare professional.”
In October, the NHS submitted plans to the National Institute for Health and Care Excellence (NICE) for a phased rollout of tirzepatide in England that would initially prioritize patients with the greatest clinical need. The first phase would see the drug available to people with a body mass index of more than 40 kg/m2 who also suffer from at least three of the main weight-related health problems: hypertension, dyslipidemia, obstructive sleep apnea, and cardiovascular disease.
“Our sincere sympathies are with the family of individual concerned,” said Alison Cave, MHRA Chief Safety Officer.
“Patient safety is our top priority and no medicine would be approved unless it met our expected standards of safety, quality, and effectiveness. Our role is to continually monitor the safety of medicines during their use, such as GLP-1 RAs. We have robust, safety monitoring and surveillance systems in place for all healthcare products.
“New medicines, such as tirzepatide, are more intensively monitored to ensure that any new safety issues are identified promptly. We strongly encourage the reporting of all suspected reactions to newer medicines, which are denoted by an inverted Black Triangle symbol.
“On the basis of the current evidence the benefits of GLP-1 RAs outweigh the potential risks when used for the licensed indications. The decision to start, continue, or stop treatments should be made jointly by patients and their doctor, based on full consideration of the benefits and risks.”
She encouraged patients and healthcare professionals to continue reporting suspected side effects to GLP-1 RAs, such as tirzepatide, through the Yellow Card Scheme. “When a safety issue is confirmed, we always act promptly to inform patients and healthcare professionals and take appropriate steps to mitigate any identified risk.”
The Department of Health and Social Care declined to comment.
Adler disclosed being involved as an unpaid investigator on an Eli Lilly–funded trial for a different drug. Sattar has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Doctors have urged caution in linking the weight loss drug tirzepatide to the death of a 58-year-old nurse from Scotland.
Susan McGowan, from North Lanarkshire, took two low-dose injections of tirzepatide (Mounjaro) over the course of about 2 weeks before her death in September.
BBC News reported that multiple organ failure, septic shock, and pancreatitis were listed on her death certificate as the immediate cause of death, with “the use of prescribed tirzepatide” recorded as a contributing factor.
McGowan worked as a nurse at University Hospital Monklands in Airdrie. A family member said that, apart from carrying a “bit of extra weight,” she had been otherwise healthy and was not taking any other medication.
It is understood that McGowan had sought medical advice before purchasing a prescription for tirzepatide through a registered UK pharmacy. However, days after administering a second injection, she went to A&E at Monklands with severe stomach pain and sickness. She died on September 4.
Expert Insights
Commenting to the Science Media Centre (SMC), Amanda Adler, MD, PhD, professor of diabetic medicine and health policy at the University of Oxford, described the nurse’s death as “sad” but said that “whether or not it was related to tirzepatide may be difficult to prove.” While tirzepatide can be associated with uncommon problems such as acute pancreatitis, “one can develop acute pancreatitis for many other reasons as well,” she said.
Naveed Sattar, MD, PhD, professor of metabolic medicine at the University of Glasgow, noted that data from multiple trials of tirzepatide, involving around 10,000 people living with diabetes or obesity, “do not suggest a higher risk of pancreatitis.” Furthermore, “the data seem to show acceptable safety thus far and a range of benefits including sizable average weight loss (near 20%), strong diabetes prevention, and considerable benefits in people living with sleep apnea,” he told the SMC.
Approved Based on Extensive Assessment
Tirzepatide, a GLP-1 receptor agonist, was approved for use as a weight loss aid in the United Kingdom in November last year by the Medicines and Healthcare products Regulatory Agency (MHRA). It lists nausea, diarrhea, and vomiting as the most common side effects, as well as hypoglycemia for patients with diabetes.
Available figures under the Yellow Card scheme up to 19 May 2024 show that there were 208 adverse drug reactions reported about tirzepatide this year, including 31 serious reactions and one suspected death of a man in his 60s.
In a statement, a spokesperson for the drug’s manufacturer, Eli Lilly, said, “Patient safety is Lilly’s top priority. We are committed to continually monitoring, evaluating, and reporting safety information for all Lilly medicines.
“Mounjaro (tirzepatide) was approved based on extensive assessment of the benefits and risks of the medicine, and we provide information about the benefits and risks of all our medicines to regulators around the world to ensure the latest information is available for prescribers. If anyone is experiencing side effects when taking any Lilly medicine, they should talk to their doctor or other healthcare professional.”
In October, the NHS submitted plans to the National Institute for Health and Care Excellence (NICE) for a phased rollout of tirzepatide in England that would initially prioritize patients with the greatest clinical need. The first phase would see the drug available to people with a body mass index of more than 40 kg/m2 who also suffer from at least three of the main weight-related health problems: hypertension, dyslipidemia, obstructive sleep apnea, and cardiovascular disease.
“Our sincere sympathies are with the family of individual concerned,” said Alison Cave, MHRA Chief Safety Officer.
“Patient safety is our top priority and no medicine would be approved unless it met our expected standards of safety, quality, and effectiveness. Our role is to continually monitor the safety of medicines during their use, such as GLP-1 RAs. We have robust, safety monitoring and surveillance systems in place for all healthcare products.
“New medicines, such as tirzepatide, are more intensively monitored to ensure that any new safety issues are identified promptly. We strongly encourage the reporting of all suspected reactions to newer medicines, which are denoted by an inverted Black Triangle symbol.
“On the basis of the current evidence the benefits of GLP-1 RAs outweigh the potential risks when used for the licensed indications. The decision to start, continue, or stop treatments should be made jointly by patients and their doctor, based on full consideration of the benefits and risks.”
She encouraged patients and healthcare professionals to continue reporting suspected side effects to GLP-1 RAs, such as tirzepatide, through the Yellow Card Scheme. “When a safety issue is confirmed, we always act promptly to inform patients and healthcare professionals and take appropriate steps to mitigate any identified risk.”
The Department of Health and Social Care declined to comment.
Adler disclosed being involved as an unpaid investigator on an Eli Lilly–funded trial for a different drug. Sattar has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
EMA Warns of Anaphylactic Reactions to MS Drug
Such reactions could occur even years after the start of treatment, the European Medicines Agency (EMA) warned.
Glatiramer acetate is a disease-modifying therapy (DMT) for relapsing MS that is given by injection.
The drug has been used for treating MS for more than 20 years, during which time, it has had a good safety profile. Common side effects are known to include vasodilation, arthralgia, anxiety, hypertonia, palpitations, and lipoatrophy.
A meeting of the EMA’s Pharmacovigilance Risk Assessment Committee (PRAC), held on July 8-11, considered evidence from an EU-wide review of all available data concerning anaphylactic reactions with glatiramer acetate. As a result, the committee concluded that the medicine is associated with a risk for anaphylactic reactions, which may occur shortly after administration or even months or years later.
Risk for Delays to Treatment
Cases involving the use of glatiramer acetate with a fatal outcome have been reported, PRAC noted.
The committee cautioned that because the initial symptoms could overlap with those of postinjection reaction, there was a risk for delay in identifying an anaphylactic reaction.
PRAC has sanctioned a direct healthcare professional communication (DHPC) to inform healthcare professionals about the risk. Patients and caregivers should be advised of the signs and symptoms of an anaphylactic reaction and the need to seek emergency care if this should occur, the committee added. In the event of such a reaction, treatment with glatiramer acetate must be discontinued, PRAC stated.
Once adopted, the DHPC for glatiramer acetate will be disseminated to healthcare professionals by the marketing authorization holders.
Anaphylactic reactions associated with the use of glatiramer acetate have been noted in medical literature for some years. A letter by members of the department of neurology at Albert Ludwig University Freiburg, Freiburg im Bresigau, Germany, published in the journal European Neurology in 2011, detailed six cases of anaphylactoid or anaphylactic reactions in patients while they were undergoing treatment with glatiramer acetate.
The authors highlighted that in one of the cases, a grade 1 anaphylactic reaction occurred 3 months after treatment with the drug was initiated.
A version of this article first appeared on Medscape.com.
Such reactions could occur even years after the start of treatment, the European Medicines Agency (EMA) warned.
Glatiramer acetate is a disease-modifying therapy (DMT) for relapsing MS that is given by injection.
The drug has been used for treating MS for more than 20 years, during which time, it has had a good safety profile. Common side effects are known to include vasodilation, arthralgia, anxiety, hypertonia, palpitations, and lipoatrophy.
A meeting of the EMA’s Pharmacovigilance Risk Assessment Committee (PRAC), held on July 8-11, considered evidence from an EU-wide review of all available data concerning anaphylactic reactions with glatiramer acetate. As a result, the committee concluded that the medicine is associated with a risk for anaphylactic reactions, which may occur shortly after administration or even months or years later.
Risk for Delays to Treatment
Cases involving the use of glatiramer acetate with a fatal outcome have been reported, PRAC noted.
The committee cautioned that because the initial symptoms could overlap with those of postinjection reaction, there was a risk for delay in identifying an anaphylactic reaction.
PRAC has sanctioned a direct healthcare professional communication (DHPC) to inform healthcare professionals about the risk. Patients and caregivers should be advised of the signs and symptoms of an anaphylactic reaction and the need to seek emergency care if this should occur, the committee added. In the event of such a reaction, treatment with glatiramer acetate must be discontinued, PRAC stated.
Once adopted, the DHPC for glatiramer acetate will be disseminated to healthcare professionals by the marketing authorization holders.
Anaphylactic reactions associated with the use of glatiramer acetate have been noted in medical literature for some years. A letter by members of the department of neurology at Albert Ludwig University Freiburg, Freiburg im Bresigau, Germany, published in the journal European Neurology in 2011, detailed six cases of anaphylactoid or anaphylactic reactions in patients while they were undergoing treatment with glatiramer acetate.
The authors highlighted that in one of the cases, a grade 1 anaphylactic reaction occurred 3 months after treatment with the drug was initiated.
A version of this article first appeared on Medscape.com.
Such reactions could occur even years after the start of treatment, the European Medicines Agency (EMA) warned.
Glatiramer acetate is a disease-modifying therapy (DMT) for relapsing MS that is given by injection.
The drug has been used for treating MS for more than 20 years, during which time, it has had a good safety profile. Common side effects are known to include vasodilation, arthralgia, anxiety, hypertonia, palpitations, and lipoatrophy.
A meeting of the EMA’s Pharmacovigilance Risk Assessment Committee (PRAC), held on July 8-11, considered evidence from an EU-wide review of all available data concerning anaphylactic reactions with glatiramer acetate. As a result, the committee concluded that the medicine is associated with a risk for anaphylactic reactions, which may occur shortly after administration or even months or years later.
Risk for Delays to Treatment
Cases involving the use of glatiramer acetate with a fatal outcome have been reported, PRAC noted.
The committee cautioned that because the initial symptoms could overlap with those of postinjection reaction, there was a risk for delay in identifying an anaphylactic reaction.
PRAC has sanctioned a direct healthcare professional communication (DHPC) to inform healthcare professionals about the risk. Patients and caregivers should be advised of the signs and symptoms of an anaphylactic reaction and the need to seek emergency care if this should occur, the committee added. In the event of such a reaction, treatment with glatiramer acetate must be discontinued, PRAC stated.
Once adopted, the DHPC for glatiramer acetate will be disseminated to healthcare professionals by the marketing authorization holders.
Anaphylactic reactions associated with the use of glatiramer acetate have been noted in medical literature for some years. A letter by members of the department of neurology at Albert Ludwig University Freiburg, Freiburg im Bresigau, Germany, published in the journal European Neurology in 2011, detailed six cases of anaphylactoid or anaphylactic reactions in patients while they were undergoing treatment with glatiramer acetate.
The authors highlighted that in one of the cases, a grade 1 anaphylactic reaction occurred 3 months after treatment with the drug was initiated.
A version of this article first appeared on Medscape.com.
Collaboration Tackles Steroid-Induced Adrenal Insufficiency
Endocrinologists in Europe and the United States have come together to produce joint guidance to help clinicians manage patients who have, or are a at risk for, glucocorticoid-induced adrenal insufficiency (GC-AI).
Publication of the guidance marks the first time that the European Society of Endocrinology (ESE) and the Endocrine Society have cooperated in producing a guideline.
The guideline “Diagnosis and therapy of glucocorticoid-induced adrenal insufficiency” is published in the May 2024 issues of the societies respective journals, the European Journal of Endocrinology and The Journal of Clinical Endocrinology & Metabolism.
Felix Beuschlein, PhD, from the ESE, who cochaired the clinical committee, told this news organization: “You would hope that this leads to a common ground for a very large number of patients.”
The risk for GC-AI is dependent on the dose, duration, and potency of the glucocorticoid; route of administration; as well as susceptibility of the individual patient. Once it develops or is suspected, careful education and management of affected patients is required.
Glucocorticoids Commonly Prescribed
“Glucocorticoid-induced adrenal insufficiency is actually a potential concern for a lot of patients,” coauthor Tobias Else, MD, of the department of internal medicine at the University of Michigan, Ann Arbor, explained to this news organization. “Roughly 1% of all people are being treated with glucocorticoids at any given time.”
“That’s a tremendous number, and it gives the scale of the situation,” added Dr. Beuschlein, director of the department of endocrinology, diabetology, and clinical nutrition at University Hospital Zürich in Switzerland. “Now, fortunately, only a very small proportion of patients who are treated with glucocorticoids do have endocrine problems, and this is what this guideline is actually concentrating on.”
Glucocorticoids are effective agents for treating autoimmune and inflammatory disorders. However, they can cause adverse reactions, particularly when administered at high doses and/or for a prolonged period.
Some studies have reported that even low-dose glucocorticoid use, such as prednisone at 2.5-7.5 mg/d, can increase the risk for cardiovascular disease, severe infections, hypertension, diabetes, osteoporosis, and fractures, as well as increase overall mortality with concurrent type 2 diabetes.
Tapering glucocorticoids can be challenging when symptoms of glucocorticoid withdrawal develop, which overlap with those of adrenal insufficiency, the guidelines stated. In general, tapering of glucocorticoids can occur more rapidly within a supraphysiological range, followed by a slower taper when on physiological glucocorticoid dosing.
The degree and persistence of hypothalamic-pituitary-adrenal (HPA) axis suppression after glucocorticoid therapy is stopped depends on overall exposure and recovery of adrenal function. “This is a quite individual situation, as you can imagine, because it’s about sex, age, and comorbidities, the kind of glucocorticoid or other medications that you’re giving,” said Dr. Beuschlein. To cover contingencies, the paper presents tables to explain management covering various eventualities.
Leonie van Hulsteijn, MD, from the department of clinical epidemiology, Leiden University Medical Center, Leiden, the Netherlands, said: “There are so many other specialties prescribing glucocorticoids; so especially the rheumatologist, the pulmonologist, the general practitioners.”
Asked by this news organization whether the guidelines might dissuade some clinicians from offering glucocorticoids, Dr. van Hulsteijn, who contributed to the guidance, said, “I don’t think it will keep them from prescribing it, but I really hope it will make them aware if somebody, after using long-term glucocorticoids, presents with complaints of adrenal insufficiency, that they will be aware and take immediate action.”
Evidence Gaps
The review team took around 2.5 years to draw up the guidance amid some concerns about the quality of the evidence base, which they mainly rated as “low” or “very low.” “I think we all, going through the literature, were quite astonished at how bad the evidence is for a problem as global as that,” said Dr. Beuschlein. “But that’s how it is — sometimes, even in the absence of strong evidence, you have to give some kind of guidance.”
Nevertheless, the authors have called for more research to establish risk factors contributing to the development of and susceptibility to adrenal insufficiency, a greater understanding of glucocorticoid withdrawal, and identification of glucocorticoids retaining immunosuppressive and anti-inflammatory properties that have less effect on HPA axis suppression and an improved adverse effect profile.
Patient-facing materials on GC-AI are also in development and will be made available via the ESE Patient Zone this month.
Next year, the societies plan to publish a joint guideline on diabetes in pregnancy. That will be followed in 2026 by guidance on arginine vasopressin resistance and arginine vasopressin deficiency and a guideline on male hypogonadism in 2027.
Funding for the development of joint guidelines was provided by the societies and did not involve support from other bodies.
Dr. Beuschlein declared funding from the German Research Funding Agency, the Swiss National Science Foundation, University Medicine Zürich, the Vontobel Foundation, the Swiss Heart Foundation, and consultancy work for Bayer AG. Dr. Else declared membership of the advisory board of Merck and Company. Dr. van Hulsteijn declared no conflicts of interest.
A version of this article appeared on Medscape.com.
Endocrinologists in Europe and the United States have come together to produce joint guidance to help clinicians manage patients who have, or are a at risk for, glucocorticoid-induced adrenal insufficiency (GC-AI).
Publication of the guidance marks the first time that the European Society of Endocrinology (ESE) and the Endocrine Society have cooperated in producing a guideline.
The guideline “Diagnosis and therapy of glucocorticoid-induced adrenal insufficiency” is published in the May 2024 issues of the societies respective journals, the European Journal of Endocrinology and The Journal of Clinical Endocrinology & Metabolism.
Felix Beuschlein, PhD, from the ESE, who cochaired the clinical committee, told this news organization: “You would hope that this leads to a common ground for a very large number of patients.”
The risk for GC-AI is dependent on the dose, duration, and potency of the glucocorticoid; route of administration; as well as susceptibility of the individual patient. Once it develops or is suspected, careful education and management of affected patients is required.
Glucocorticoids Commonly Prescribed
“Glucocorticoid-induced adrenal insufficiency is actually a potential concern for a lot of patients,” coauthor Tobias Else, MD, of the department of internal medicine at the University of Michigan, Ann Arbor, explained to this news organization. “Roughly 1% of all people are being treated with glucocorticoids at any given time.”
“That’s a tremendous number, and it gives the scale of the situation,” added Dr. Beuschlein, director of the department of endocrinology, diabetology, and clinical nutrition at University Hospital Zürich in Switzerland. “Now, fortunately, only a very small proportion of patients who are treated with glucocorticoids do have endocrine problems, and this is what this guideline is actually concentrating on.”
Glucocorticoids are effective agents for treating autoimmune and inflammatory disorders. However, they can cause adverse reactions, particularly when administered at high doses and/or for a prolonged period.
Some studies have reported that even low-dose glucocorticoid use, such as prednisone at 2.5-7.5 mg/d, can increase the risk for cardiovascular disease, severe infections, hypertension, diabetes, osteoporosis, and fractures, as well as increase overall mortality with concurrent type 2 diabetes.
Tapering glucocorticoids can be challenging when symptoms of glucocorticoid withdrawal develop, which overlap with those of adrenal insufficiency, the guidelines stated. In general, tapering of glucocorticoids can occur more rapidly within a supraphysiological range, followed by a slower taper when on physiological glucocorticoid dosing.
The degree and persistence of hypothalamic-pituitary-adrenal (HPA) axis suppression after glucocorticoid therapy is stopped depends on overall exposure and recovery of adrenal function. “This is a quite individual situation, as you can imagine, because it’s about sex, age, and comorbidities, the kind of glucocorticoid or other medications that you’re giving,” said Dr. Beuschlein. To cover contingencies, the paper presents tables to explain management covering various eventualities.
Leonie van Hulsteijn, MD, from the department of clinical epidemiology, Leiden University Medical Center, Leiden, the Netherlands, said: “There are so many other specialties prescribing glucocorticoids; so especially the rheumatologist, the pulmonologist, the general practitioners.”
Asked by this news organization whether the guidelines might dissuade some clinicians from offering glucocorticoids, Dr. van Hulsteijn, who contributed to the guidance, said, “I don’t think it will keep them from prescribing it, but I really hope it will make them aware if somebody, after using long-term glucocorticoids, presents with complaints of adrenal insufficiency, that they will be aware and take immediate action.”
Evidence Gaps
The review team took around 2.5 years to draw up the guidance amid some concerns about the quality of the evidence base, which they mainly rated as “low” or “very low.” “I think we all, going through the literature, were quite astonished at how bad the evidence is for a problem as global as that,” said Dr. Beuschlein. “But that’s how it is — sometimes, even in the absence of strong evidence, you have to give some kind of guidance.”
Nevertheless, the authors have called for more research to establish risk factors contributing to the development of and susceptibility to adrenal insufficiency, a greater understanding of glucocorticoid withdrawal, and identification of glucocorticoids retaining immunosuppressive and anti-inflammatory properties that have less effect on HPA axis suppression and an improved adverse effect profile.
Patient-facing materials on GC-AI are also in development and will be made available via the ESE Patient Zone this month.
Next year, the societies plan to publish a joint guideline on diabetes in pregnancy. That will be followed in 2026 by guidance on arginine vasopressin resistance and arginine vasopressin deficiency and a guideline on male hypogonadism in 2027.
Funding for the development of joint guidelines was provided by the societies and did not involve support from other bodies.
Dr. Beuschlein declared funding from the German Research Funding Agency, the Swiss National Science Foundation, University Medicine Zürich, the Vontobel Foundation, the Swiss Heart Foundation, and consultancy work for Bayer AG. Dr. Else declared membership of the advisory board of Merck and Company. Dr. van Hulsteijn declared no conflicts of interest.
A version of this article appeared on Medscape.com.
Endocrinologists in Europe and the United States have come together to produce joint guidance to help clinicians manage patients who have, or are a at risk for, glucocorticoid-induced adrenal insufficiency (GC-AI).
Publication of the guidance marks the first time that the European Society of Endocrinology (ESE) and the Endocrine Society have cooperated in producing a guideline.
The guideline “Diagnosis and therapy of glucocorticoid-induced adrenal insufficiency” is published in the May 2024 issues of the societies respective journals, the European Journal of Endocrinology and The Journal of Clinical Endocrinology & Metabolism.
Felix Beuschlein, PhD, from the ESE, who cochaired the clinical committee, told this news organization: “You would hope that this leads to a common ground for a very large number of patients.”
The risk for GC-AI is dependent on the dose, duration, and potency of the glucocorticoid; route of administration; as well as susceptibility of the individual patient. Once it develops or is suspected, careful education and management of affected patients is required.
Glucocorticoids Commonly Prescribed
“Glucocorticoid-induced adrenal insufficiency is actually a potential concern for a lot of patients,” coauthor Tobias Else, MD, of the department of internal medicine at the University of Michigan, Ann Arbor, explained to this news organization. “Roughly 1% of all people are being treated with glucocorticoids at any given time.”
“That’s a tremendous number, and it gives the scale of the situation,” added Dr. Beuschlein, director of the department of endocrinology, diabetology, and clinical nutrition at University Hospital Zürich in Switzerland. “Now, fortunately, only a very small proportion of patients who are treated with glucocorticoids do have endocrine problems, and this is what this guideline is actually concentrating on.”
Glucocorticoids are effective agents for treating autoimmune and inflammatory disorders. However, they can cause adverse reactions, particularly when administered at high doses and/or for a prolonged period.
Some studies have reported that even low-dose glucocorticoid use, such as prednisone at 2.5-7.5 mg/d, can increase the risk for cardiovascular disease, severe infections, hypertension, diabetes, osteoporosis, and fractures, as well as increase overall mortality with concurrent type 2 diabetes.
Tapering glucocorticoids can be challenging when symptoms of glucocorticoid withdrawal develop, which overlap with those of adrenal insufficiency, the guidelines stated. In general, tapering of glucocorticoids can occur more rapidly within a supraphysiological range, followed by a slower taper when on physiological glucocorticoid dosing.
The degree and persistence of hypothalamic-pituitary-adrenal (HPA) axis suppression after glucocorticoid therapy is stopped depends on overall exposure and recovery of adrenal function. “This is a quite individual situation, as you can imagine, because it’s about sex, age, and comorbidities, the kind of glucocorticoid or other medications that you’re giving,” said Dr. Beuschlein. To cover contingencies, the paper presents tables to explain management covering various eventualities.
Leonie van Hulsteijn, MD, from the department of clinical epidemiology, Leiden University Medical Center, Leiden, the Netherlands, said: “There are so many other specialties prescribing glucocorticoids; so especially the rheumatologist, the pulmonologist, the general practitioners.”
Asked by this news organization whether the guidelines might dissuade some clinicians from offering glucocorticoids, Dr. van Hulsteijn, who contributed to the guidance, said, “I don’t think it will keep them from prescribing it, but I really hope it will make them aware if somebody, after using long-term glucocorticoids, presents with complaints of adrenal insufficiency, that they will be aware and take immediate action.”
Evidence Gaps
The review team took around 2.5 years to draw up the guidance amid some concerns about the quality of the evidence base, which they mainly rated as “low” or “very low.” “I think we all, going through the literature, were quite astonished at how bad the evidence is for a problem as global as that,” said Dr. Beuschlein. “But that’s how it is — sometimes, even in the absence of strong evidence, you have to give some kind of guidance.”
Nevertheless, the authors have called for more research to establish risk factors contributing to the development of and susceptibility to adrenal insufficiency, a greater understanding of glucocorticoid withdrawal, and identification of glucocorticoids retaining immunosuppressive and anti-inflammatory properties that have less effect on HPA axis suppression and an improved adverse effect profile.
Patient-facing materials on GC-AI are also in development and will be made available via the ESE Patient Zone this month.
Next year, the societies plan to publish a joint guideline on diabetes in pregnancy. That will be followed in 2026 by guidance on arginine vasopressin resistance and arginine vasopressin deficiency and a guideline on male hypogonadism in 2027.
Funding for the development of joint guidelines was provided by the societies and did not involve support from other bodies.
Dr. Beuschlein declared funding from the German Research Funding Agency, the Swiss National Science Foundation, University Medicine Zürich, the Vontobel Foundation, the Swiss Heart Foundation, and consultancy work for Bayer AG. Dr. Else declared membership of the advisory board of Merck and Company. Dr. van Hulsteijn declared no conflicts of interest.
A version of this article appeared on Medscape.com.
European Scientists Assess Avian Flu Pandemic Risk
As avian influenza continues to spread among wild bird populations in the European Union (EU), scientists have described a wide range of factors that could drive the virus to spread efficiently among humans, thereby increasing its pandemic potential.
Although transmission of avian influenza A(H5N1) from infected birds to humans is rare, “new strains carrying potential mutations for mammalian adaptation” could occur, according to a report issued on April 3 by the European Centre for Disease Prevention and Control and the European Food Safety Authority. The analysis identified a threat of strains currently circulating outside Europe that could enter the EU and the wider European Economic Area (EEA).
“If avian A(H5N1) influenza viruses acquire the ability to spread efficiently among humans, large-scale transmission could occur due to the lack of immune defenses against H5 viruses in humans,” the report warned.
Evolution of Avian Influenza Remains Hard to Predict
However, despite many occurrences of human exposure to avian influenza since 2020, “no symptomatic or productive infection in a human has been identified in the EU/EEA,” the scientists stated. Furthermore, after almost three decades of human exposure to the A(H5N1) virus of the Gs/GD lineage, the virus has not yet acquired the mutations required for airborne transmissibility between humans. However, it remains “difficult to predict the evolutionary direction the virus will take in the future,” the scientists assessed.
“Clearly, humans are being exposed in the current USA cattle outbreak,” Professor James Wood, infectious disease epidemiologist at the University of Cambridge, United Kingdom, told this news organization. “But, arguably, what is more significant is how few cases there have been with this virus lineage and its close relatives, despite massive global exposures over the last 3 years. All diagnosed human cases seem to have been singletons, with no evidence of human-to-human transmission.”
Ian Jones, professor of virology at the University of Reading, United Kingdom, sees no evidence of an imminent spillover of avian influenza from birds. But he told this news organization: “The trouble is, the clock resets every minute. Every time the virus has come out of a bird and gone somewhere, the clock is reset. So you can never say that just because it hasn’t happened since whenever, it’s never going to happen.”
Preventive Measures Recommended
The European report recommended a range of cautionary measures that included enhanced surveillance, access to rapid diagnostics, and sharing of genetic sequence data. It urged EU authorities to work together, adopting a One Health perspective, to limit the exposure of mammals, including humans, to avian influenza viruses.
Sarah Pitt, a microbiologist at the University of Brighton, United Kingdom, said the emphasis on authorities taking a One Health approach was sound. “You’re looking at humans, animals, plants, and the environment and how they’re all closely interacted,” she told this news organization. “Putting all those things together is actually going to be good for human health. So they’ve mentioned One Health a lot and I’m sure that’s on purpose because it’s the latest buzzword, and presumably it’s a way of getting governments to take it seriously.”
Overall, Dr. Pitt believes the document is designed to move zoonotic infectious diseases a bit higher up the agenda. “They should have been higher up the agenda before COVID,” she said.
The report also called for consideration of preventative measures, such as vaccination of poultry flocks.
Overall, Dr. Jones assesses the European report as “a reworking of what’s been pretty well covered over the years.” Despite extensive work by scientists in the field, he said: “I’m not sure we’re any better at predicting an emerging virus than we’ve ever been. I would point out that we didn’t spot SARS-CoV-2 coming, even though we had SARS-CoV-1 a few years earlier. Nobody spotted the 2009 pandemic from influenza, even though there was a lot of surveillance around at the time.”
A version of this article appeared on Medscape.com.
As avian influenza continues to spread among wild bird populations in the European Union (EU), scientists have described a wide range of factors that could drive the virus to spread efficiently among humans, thereby increasing its pandemic potential.
Although transmission of avian influenza A(H5N1) from infected birds to humans is rare, “new strains carrying potential mutations for mammalian adaptation” could occur, according to a report issued on April 3 by the European Centre for Disease Prevention and Control and the European Food Safety Authority. The analysis identified a threat of strains currently circulating outside Europe that could enter the EU and the wider European Economic Area (EEA).
“If avian A(H5N1) influenza viruses acquire the ability to spread efficiently among humans, large-scale transmission could occur due to the lack of immune defenses against H5 viruses in humans,” the report warned.
Evolution of Avian Influenza Remains Hard to Predict
However, despite many occurrences of human exposure to avian influenza since 2020, “no symptomatic or productive infection in a human has been identified in the EU/EEA,” the scientists stated. Furthermore, after almost three decades of human exposure to the A(H5N1) virus of the Gs/GD lineage, the virus has not yet acquired the mutations required for airborne transmissibility between humans. However, it remains “difficult to predict the evolutionary direction the virus will take in the future,” the scientists assessed.
“Clearly, humans are being exposed in the current USA cattle outbreak,” Professor James Wood, infectious disease epidemiologist at the University of Cambridge, United Kingdom, told this news organization. “But, arguably, what is more significant is how few cases there have been with this virus lineage and its close relatives, despite massive global exposures over the last 3 years. All diagnosed human cases seem to have been singletons, with no evidence of human-to-human transmission.”
Ian Jones, professor of virology at the University of Reading, United Kingdom, sees no evidence of an imminent spillover of avian influenza from birds. But he told this news organization: “The trouble is, the clock resets every minute. Every time the virus has come out of a bird and gone somewhere, the clock is reset. So you can never say that just because it hasn’t happened since whenever, it’s never going to happen.”
Preventive Measures Recommended
The European report recommended a range of cautionary measures that included enhanced surveillance, access to rapid diagnostics, and sharing of genetic sequence data. It urged EU authorities to work together, adopting a One Health perspective, to limit the exposure of mammals, including humans, to avian influenza viruses.
Sarah Pitt, a microbiologist at the University of Brighton, United Kingdom, said the emphasis on authorities taking a One Health approach was sound. “You’re looking at humans, animals, plants, and the environment and how they’re all closely interacted,” she told this news organization. “Putting all those things together is actually going to be good for human health. So they’ve mentioned One Health a lot and I’m sure that’s on purpose because it’s the latest buzzword, and presumably it’s a way of getting governments to take it seriously.”
Overall, Dr. Pitt believes the document is designed to move zoonotic infectious diseases a bit higher up the agenda. “They should have been higher up the agenda before COVID,” she said.
The report also called for consideration of preventative measures, such as vaccination of poultry flocks.
Overall, Dr. Jones assesses the European report as “a reworking of what’s been pretty well covered over the years.” Despite extensive work by scientists in the field, he said: “I’m not sure we’re any better at predicting an emerging virus than we’ve ever been. I would point out that we didn’t spot SARS-CoV-2 coming, even though we had SARS-CoV-1 a few years earlier. Nobody spotted the 2009 pandemic from influenza, even though there was a lot of surveillance around at the time.”
A version of this article appeared on Medscape.com.
As avian influenza continues to spread among wild bird populations in the European Union (EU), scientists have described a wide range of factors that could drive the virus to spread efficiently among humans, thereby increasing its pandemic potential.
Although transmission of avian influenza A(H5N1) from infected birds to humans is rare, “new strains carrying potential mutations for mammalian adaptation” could occur, according to a report issued on April 3 by the European Centre for Disease Prevention and Control and the European Food Safety Authority. The analysis identified a threat of strains currently circulating outside Europe that could enter the EU and the wider European Economic Area (EEA).
“If avian A(H5N1) influenza viruses acquire the ability to spread efficiently among humans, large-scale transmission could occur due to the lack of immune defenses against H5 viruses in humans,” the report warned.
Evolution of Avian Influenza Remains Hard to Predict
However, despite many occurrences of human exposure to avian influenza since 2020, “no symptomatic or productive infection in a human has been identified in the EU/EEA,” the scientists stated. Furthermore, after almost three decades of human exposure to the A(H5N1) virus of the Gs/GD lineage, the virus has not yet acquired the mutations required for airborne transmissibility between humans. However, it remains “difficult to predict the evolutionary direction the virus will take in the future,” the scientists assessed.
“Clearly, humans are being exposed in the current USA cattle outbreak,” Professor James Wood, infectious disease epidemiologist at the University of Cambridge, United Kingdom, told this news organization. “But, arguably, what is more significant is how few cases there have been with this virus lineage and its close relatives, despite massive global exposures over the last 3 years. All diagnosed human cases seem to have been singletons, with no evidence of human-to-human transmission.”
Ian Jones, professor of virology at the University of Reading, United Kingdom, sees no evidence of an imminent spillover of avian influenza from birds. But he told this news organization: “The trouble is, the clock resets every minute. Every time the virus has come out of a bird and gone somewhere, the clock is reset. So you can never say that just because it hasn’t happened since whenever, it’s never going to happen.”
Preventive Measures Recommended
The European report recommended a range of cautionary measures that included enhanced surveillance, access to rapid diagnostics, and sharing of genetic sequence data. It urged EU authorities to work together, adopting a One Health perspective, to limit the exposure of mammals, including humans, to avian influenza viruses.
Sarah Pitt, a microbiologist at the University of Brighton, United Kingdom, said the emphasis on authorities taking a One Health approach was sound. “You’re looking at humans, animals, plants, and the environment and how they’re all closely interacted,” she told this news organization. “Putting all those things together is actually going to be good for human health. So they’ve mentioned One Health a lot and I’m sure that’s on purpose because it’s the latest buzzword, and presumably it’s a way of getting governments to take it seriously.”
Overall, Dr. Pitt believes the document is designed to move zoonotic infectious diseases a bit higher up the agenda. “They should have been higher up the agenda before COVID,” she said.
The report also called for consideration of preventative measures, such as vaccination of poultry flocks.
Overall, Dr. Jones assesses the European report as “a reworking of what’s been pretty well covered over the years.” Despite extensive work by scientists in the field, he said: “I’m not sure we’re any better at predicting an emerging virus than we’ve ever been. I would point out that we didn’t spot SARS-CoV-2 coming, even though we had SARS-CoV-1 a few years earlier. Nobody spotted the 2009 pandemic from influenza, even though there was a lot of surveillance around at the time.”
A version of this article appeared on Medscape.com.
EU Backs First Oral Monotherapy for Adults With PNH
The decision was hailed as a first step toward enabling patient access in European Union countries following a March 21 meeting of the Committee for Medicinal Products for Human Use (CHMP).
PNH is a rare, debilitating, and potentially life-threatening genetic disorder that causes hemolytic anemia. Symptoms of the disease include fatigue, body pain, blood clots, bleeding, and shortness of breath. The standard treatment is anti-C5 monoclonal antibodies (eculizumab or ravulizumab) via subcutaneous or intravenous infusion. However, a minority of patients with PNH who are treated with these complement inhibitors encounter residual hemolytic anemia and require red blood cell transfusions.
The active substance of Fabhalta is iptacopan, a proximal complement inhibitor. Iptacopan targets factor B to selectively inhibit the alternative complement pathway and control both C3-mediated extravascular hemolysis and terminal complement-mediated intravascular hemolysis.
Superior Results in Phase 3 Trials
The decision to grant a marketing authorization was taken following a review of two phase 3 trials. The main study was a randomized, open-label, active comparator trial involving 97 patients with PNH who had residual anemia despite receiving treatment with anti-C5 monoclonal antibodies for the previous 6 months. Of the trial participants, 62 received iptacopan monotherapy and 35 continued their anti-C5 regimen for 24 weeks.
Treatment with Fabhalta was found to be significantly superior to the anti-C5 regimen, with 51 of 60 patients who could be evaluated achieving hemoglobin improvement (≥ 2 g/dL) and 42 achieving sustained hemoglobin levels (≥ 12 g/dL) without transfusion, compared with no patients who continued treatment with anti-C5 monoclonal antibodies. Also, 59 of 62 patients treated with Fabhalta did not require blood transfusions between day 14 and day 168, compared with 14 of 35 patients in the anti-C5 group.
The second trial was a single-arm study involving 40 PNH patients who had not previously been treated with a complement inhibitor. Following treatment with Fabhalta, 31 of 33 patients who could be evaluated achieved hemoglobin improvement (≥ 2 g/dL) at week 24, whereas 19 achieved sustained hemoglobin levels (≥ 12 g/dL) without transfusion.
The most common side effects of Fabhalta are upper respiratory tract infection, headache, and diarrhea.
The CHMP stressed that Fabhalta should be prescribed by physicians who are experienced in the management of patients with hematologic disorders.
Fabhalta was supported through the EMA’s Priority Medicines (PRIME) scheme, which provides regulatory support for promising medicines with the potential to address unmet medical needs. The CHMP’s recommendation has been sent to the European Commission for a final decision.
Novartis said in a company statement on March 22 that, if approved, Fabhalta would be the first oral monotherapy available to PNH patients in Europe.
A version of this article appeared on Medscape.com.
The decision was hailed as a first step toward enabling patient access in European Union countries following a March 21 meeting of the Committee for Medicinal Products for Human Use (CHMP).
PNH is a rare, debilitating, and potentially life-threatening genetic disorder that causes hemolytic anemia. Symptoms of the disease include fatigue, body pain, blood clots, bleeding, and shortness of breath. The standard treatment is anti-C5 monoclonal antibodies (eculizumab or ravulizumab) via subcutaneous or intravenous infusion. However, a minority of patients with PNH who are treated with these complement inhibitors encounter residual hemolytic anemia and require red blood cell transfusions.
The active substance of Fabhalta is iptacopan, a proximal complement inhibitor. Iptacopan targets factor B to selectively inhibit the alternative complement pathway and control both C3-mediated extravascular hemolysis and terminal complement-mediated intravascular hemolysis.
Superior Results in Phase 3 Trials
The decision to grant a marketing authorization was taken following a review of two phase 3 trials. The main study was a randomized, open-label, active comparator trial involving 97 patients with PNH who had residual anemia despite receiving treatment with anti-C5 monoclonal antibodies for the previous 6 months. Of the trial participants, 62 received iptacopan monotherapy and 35 continued their anti-C5 regimen for 24 weeks.
Treatment with Fabhalta was found to be significantly superior to the anti-C5 regimen, with 51 of 60 patients who could be evaluated achieving hemoglobin improvement (≥ 2 g/dL) and 42 achieving sustained hemoglobin levels (≥ 12 g/dL) without transfusion, compared with no patients who continued treatment with anti-C5 monoclonal antibodies. Also, 59 of 62 patients treated with Fabhalta did not require blood transfusions between day 14 and day 168, compared with 14 of 35 patients in the anti-C5 group.
The second trial was a single-arm study involving 40 PNH patients who had not previously been treated with a complement inhibitor. Following treatment with Fabhalta, 31 of 33 patients who could be evaluated achieved hemoglobin improvement (≥ 2 g/dL) at week 24, whereas 19 achieved sustained hemoglobin levels (≥ 12 g/dL) without transfusion.
The most common side effects of Fabhalta are upper respiratory tract infection, headache, and diarrhea.
The CHMP stressed that Fabhalta should be prescribed by physicians who are experienced in the management of patients with hematologic disorders.
Fabhalta was supported through the EMA’s Priority Medicines (PRIME) scheme, which provides regulatory support for promising medicines with the potential to address unmet medical needs. The CHMP’s recommendation has been sent to the European Commission for a final decision.
Novartis said in a company statement on March 22 that, if approved, Fabhalta would be the first oral monotherapy available to PNH patients in Europe.
A version of this article appeared on Medscape.com.
The decision was hailed as a first step toward enabling patient access in European Union countries following a March 21 meeting of the Committee for Medicinal Products for Human Use (CHMP).
PNH is a rare, debilitating, and potentially life-threatening genetic disorder that causes hemolytic anemia. Symptoms of the disease include fatigue, body pain, blood clots, bleeding, and shortness of breath. The standard treatment is anti-C5 monoclonal antibodies (eculizumab or ravulizumab) via subcutaneous or intravenous infusion. However, a minority of patients with PNH who are treated with these complement inhibitors encounter residual hemolytic anemia and require red blood cell transfusions.
The active substance of Fabhalta is iptacopan, a proximal complement inhibitor. Iptacopan targets factor B to selectively inhibit the alternative complement pathway and control both C3-mediated extravascular hemolysis and terminal complement-mediated intravascular hemolysis.
Superior Results in Phase 3 Trials
The decision to grant a marketing authorization was taken following a review of two phase 3 trials. The main study was a randomized, open-label, active comparator trial involving 97 patients with PNH who had residual anemia despite receiving treatment with anti-C5 monoclonal antibodies for the previous 6 months. Of the trial participants, 62 received iptacopan monotherapy and 35 continued their anti-C5 regimen for 24 weeks.
Treatment with Fabhalta was found to be significantly superior to the anti-C5 regimen, with 51 of 60 patients who could be evaluated achieving hemoglobin improvement (≥ 2 g/dL) and 42 achieving sustained hemoglobin levels (≥ 12 g/dL) without transfusion, compared with no patients who continued treatment with anti-C5 monoclonal antibodies. Also, 59 of 62 patients treated with Fabhalta did not require blood transfusions between day 14 and day 168, compared with 14 of 35 patients in the anti-C5 group.
The second trial was a single-arm study involving 40 PNH patients who had not previously been treated with a complement inhibitor. Following treatment with Fabhalta, 31 of 33 patients who could be evaluated achieved hemoglobin improvement (≥ 2 g/dL) at week 24, whereas 19 achieved sustained hemoglobin levels (≥ 12 g/dL) without transfusion.
The most common side effects of Fabhalta are upper respiratory tract infection, headache, and diarrhea.
The CHMP stressed that Fabhalta should be prescribed by physicians who are experienced in the management of patients with hematologic disorders.
Fabhalta was supported through the EMA’s Priority Medicines (PRIME) scheme, which provides regulatory support for promising medicines with the potential to address unmet medical needs. The CHMP’s recommendation has been sent to the European Commission for a final decision.
Novartis said in a company statement on March 22 that, if approved, Fabhalta would be the first oral monotherapy available to PNH patients in Europe.
A version of this article appeared on Medscape.com.
The Ghost Research Haunting Nordic Medical Trials
Campaigners for greater transparency in medical science have reiterated calls for more to be done to avoid “medical research waste” after an investigation found that results from more than a fifth of clinical trials across five Nordic countries have never been made public.
Nonpublication of clinical trial results wastes public money, harms patients, and undermines public health, the researchers said.
There is already a well-defined ethical responsibility to publish trial results. Article 36 of the Declaration of Helsinki on Ethical Principles for Medical Research Involving Human Subjects states that “researchers have a duty to make publicly available the results of their research on human subjects,” and World Health Organization best practice protocols call for results to be uploaded onto trial registries within 12 months of trial completion.
Research Waste Is a ‘Pervasive Problem’
So, how and why do so many trials end up gathering dust in a drawer? The latest study, published February 5 as a preprint, evaluated the reporting outcomes of 2113 clinical trials at medical universities and university hospitals in Nordic countries between 2016 and 2019. It found that across the five countries, 22% of all clinical trial results had not been shared. Furthermore, only 27% of all trial results were made public, either on registries or in journals, within 12 months. Even 2 years after trials ended, only around half of results (51.7%) had been put into the public domain.
The authors concluded that missing and delayed results from academically-led clinical trials was a “pervasive problem” in Nordic countries and that institutions, funding bodies, and policymakers needed to ensure that regulations around reporting results were adhered to so that important findings are not lost.
Study first author, Gustav Nilsonne, MD, PHD, from the Department of Clinical Neuroscience at the Karolinska Institutet, Sweden, told this news organization: “Most people I talk to — most colleagues who are clinical scientists — tend to think that the main reason is that negative results are not as interesting to publish and therefore they get lower priority, and they get published later and sometimes not at all.”
Experts stressed that the problem is not confined to Nordic countries and that wasted medical research persists elsewhere in Europe and remains a global problem. For instance, a report published in the Journal of Clinical Epidemiology found that 30% of German trials completed between 2014 and 2017 remained unpublished 5 years after completion.
The Case for Laws, Monitoring, and Fines
Till Bruckner, PHD, from TranspariMED, which campaigns to end evidence distortion in medicine, told this news organization: “What is needed to comprehensively fix the problem is a national legal requirement to make all trial results public, coupled with effective monitoring, and followed by sanctions in the rare cases where institutions refuse to comply.”
Dr. Nilsonne added: “We have argued that the sponsors need to take greater responsibility, but also that there needs to be somebody whose job it is to monitor clinical trials reporting. It shouldn’t have to be that we do this as researchers on a shoestring with no dedicated resources. It should be somebody’s job.”
Since January 31, 2023, all initial clinical trial applications in the European Union must be submitted through the EU Clinical Trials Information System. Dr. Bruckner said that “the picture is not yet clear” in Europe, as the first trial results under the system are not expected until later this year. Even then, enforcement lies with regulators in individual countries. And while Denmark has already indicated it will enforce the regulations, he warned that other countries “might turn a blind eye.”
He pointed out that existing laws don’t apply to all types of trials. “That means that for many trials, nobody is legally responsible for ensuring that results are made public, and no government agency has any oversight or mandate,” he said.
Outside the EU, the United Kingdom has helped lead the way through the NHS Health Research Authority (HRA), which registers trials run in the country. One year after a trial has been completed, the HRA checks to see if the results have been uploaded to the registry and issues reminders if they haven’t.
In an update of its work in January, the authority said that compliance had hovered at just below 90% between 2018 and 2021 but that it was working to increase this to 100% by working with stakeholders across the research sector.
Dr. Nilsonne considers the UK system of central registration and follow-up an attractive option. “I would love to see something along those lines in other countries too,” he said.
‘Rampant Noncompliance’ in the United States
In the United States, a requirement to make trial results public is backed by law. Despite this, there’s evidence of “rampant noncompliance” and minimal government action, according to Megan Curtin from Universities Allied for Essential Medicines (UAEM), which has been tracking the issue in the United States and working to push universities and others to make their findings available.
The US Food and Drug Administration (FDA) shares responsibility with the National Institutes of Health for enforcement of clinical trial results reporting, but the UAEM says nearly 4000 trials are currently out of compliance with reporting requirements. In January last year, the UAEM copublished a report with the National Center for Health Research and TranspariMED, which found that 3627 American children participated in clinical trials whose results remain unreported.
The FDA can levy a fine of up to $10,000 USD for a violation of the law, but UAEM said that, as of January 2023, the FDA had sent only 92 preliminary notices of noncompliance and four notices of noncompliance. “A clear difference between the EU field of clinical trial operation and US clinical trials is that there are clear laws for reporting within 12 months, which can be enforced, but they’re not being enforced by the FDA,” Ms. Curtin told this news organization.
The UAEM is pushing the FDA to issue a minimum of 250 preliminary notices of noncompliance each year to noncompliant trial sponsors.
Dr. Nilsonne said: “I do believe we have a great responsibility to the patients that do contribute. We need to make sure that the harms and risks that a clinical trial entails are really balanced by knowledge gain, and if the results are never reported, then we can’t have a knowledge gain.”
A version of this article appeared on Medscape.com.
Campaigners for greater transparency in medical science have reiterated calls for more to be done to avoid “medical research waste” after an investigation found that results from more than a fifth of clinical trials across five Nordic countries have never been made public.
Nonpublication of clinical trial results wastes public money, harms patients, and undermines public health, the researchers said.
There is already a well-defined ethical responsibility to publish trial results. Article 36 of the Declaration of Helsinki on Ethical Principles for Medical Research Involving Human Subjects states that “researchers have a duty to make publicly available the results of their research on human subjects,” and World Health Organization best practice protocols call for results to be uploaded onto trial registries within 12 months of trial completion.
Research Waste Is a ‘Pervasive Problem’
So, how and why do so many trials end up gathering dust in a drawer? The latest study, published February 5 as a preprint, evaluated the reporting outcomes of 2113 clinical trials at medical universities and university hospitals in Nordic countries between 2016 and 2019. It found that across the five countries, 22% of all clinical trial results had not been shared. Furthermore, only 27% of all trial results were made public, either on registries or in journals, within 12 months. Even 2 years after trials ended, only around half of results (51.7%) had been put into the public domain.
The authors concluded that missing and delayed results from academically-led clinical trials was a “pervasive problem” in Nordic countries and that institutions, funding bodies, and policymakers needed to ensure that regulations around reporting results were adhered to so that important findings are not lost.
Study first author, Gustav Nilsonne, MD, PHD, from the Department of Clinical Neuroscience at the Karolinska Institutet, Sweden, told this news organization: “Most people I talk to — most colleagues who are clinical scientists — tend to think that the main reason is that negative results are not as interesting to publish and therefore they get lower priority, and they get published later and sometimes not at all.”
Experts stressed that the problem is not confined to Nordic countries and that wasted medical research persists elsewhere in Europe and remains a global problem. For instance, a report published in the Journal of Clinical Epidemiology found that 30% of German trials completed between 2014 and 2017 remained unpublished 5 years after completion.
The Case for Laws, Monitoring, and Fines
Till Bruckner, PHD, from TranspariMED, which campaigns to end evidence distortion in medicine, told this news organization: “What is needed to comprehensively fix the problem is a national legal requirement to make all trial results public, coupled with effective monitoring, and followed by sanctions in the rare cases where institutions refuse to comply.”
Dr. Nilsonne added: “We have argued that the sponsors need to take greater responsibility, but also that there needs to be somebody whose job it is to monitor clinical trials reporting. It shouldn’t have to be that we do this as researchers on a shoestring with no dedicated resources. It should be somebody’s job.”
Since January 31, 2023, all initial clinical trial applications in the European Union must be submitted through the EU Clinical Trials Information System. Dr. Bruckner said that “the picture is not yet clear” in Europe, as the first trial results under the system are not expected until later this year. Even then, enforcement lies with regulators in individual countries. And while Denmark has already indicated it will enforce the regulations, he warned that other countries “might turn a blind eye.”
He pointed out that existing laws don’t apply to all types of trials. “That means that for many trials, nobody is legally responsible for ensuring that results are made public, and no government agency has any oversight or mandate,” he said.
Outside the EU, the United Kingdom has helped lead the way through the NHS Health Research Authority (HRA), which registers trials run in the country. One year after a trial has been completed, the HRA checks to see if the results have been uploaded to the registry and issues reminders if they haven’t.
In an update of its work in January, the authority said that compliance had hovered at just below 90% between 2018 and 2021 but that it was working to increase this to 100% by working with stakeholders across the research sector.
Dr. Nilsonne considers the UK system of central registration and follow-up an attractive option. “I would love to see something along those lines in other countries too,” he said.
‘Rampant Noncompliance’ in the United States
In the United States, a requirement to make trial results public is backed by law. Despite this, there’s evidence of “rampant noncompliance” and minimal government action, according to Megan Curtin from Universities Allied for Essential Medicines (UAEM), which has been tracking the issue in the United States and working to push universities and others to make their findings available.
The US Food and Drug Administration (FDA) shares responsibility with the National Institutes of Health for enforcement of clinical trial results reporting, but the UAEM says nearly 4000 trials are currently out of compliance with reporting requirements. In January last year, the UAEM copublished a report with the National Center for Health Research and TranspariMED, which found that 3627 American children participated in clinical trials whose results remain unreported.
The FDA can levy a fine of up to $10,000 USD for a violation of the law, but UAEM said that, as of January 2023, the FDA had sent only 92 preliminary notices of noncompliance and four notices of noncompliance. “A clear difference between the EU field of clinical trial operation and US clinical trials is that there are clear laws for reporting within 12 months, which can be enforced, but they’re not being enforced by the FDA,” Ms. Curtin told this news organization.
The UAEM is pushing the FDA to issue a minimum of 250 preliminary notices of noncompliance each year to noncompliant trial sponsors.
Dr. Nilsonne said: “I do believe we have a great responsibility to the patients that do contribute. We need to make sure that the harms and risks that a clinical trial entails are really balanced by knowledge gain, and if the results are never reported, then we can’t have a knowledge gain.”
A version of this article appeared on Medscape.com.
Campaigners for greater transparency in medical science have reiterated calls for more to be done to avoid “medical research waste” after an investigation found that results from more than a fifth of clinical trials across five Nordic countries have never been made public.
Nonpublication of clinical trial results wastes public money, harms patients, and undermines public health, the researchers said.
There is already a well-defined ethical responsibility to publish trial results. Article 36 of the Declaration of Helsinki on Ethical Principles for Medical Research Involving Human Subjects states that “researchers have a duty to make publicly available the results of their research on human subjects,” and World Health Organization best practice protocols call for results to be uploaded onto trial registries within 12 months of trial completion.
Research Waste Is a ‘Pervasive Problem’
So, how and why do so many trials end up gathering dust in a drawer? The latest study, published February 5 as a preprint, evaluated the reporting outcomes of 2113 clinical trials at medical universities and university hospitals in Nordic countries between 2016 and 2019. It found that across the five countries, 22% of all clinical trial results had not been shared. Furthermore, only 27% of all trial results were made public, either on registries or in journals, within 12 months. Even 2 years after trials ended, only around half of results (51.7%) had been put into the public domain.
The authors concluded that missing and delayed results from academically-led clinical trials was a “pervasive problem” in Nordic countries and that institutions, funding bodies, and policymakers needed to ensure that regulations around reporting results were adhered to so that important findings are not lost.
Study first author, Gustav Nilsonne, MD, PHD, from the Department of Clinical Neuroscience at the Karolinska Institutet, Sweden, told this news organization: “Most people I talk to — most colleagues who are clinical scientists — tend to think that the main reason is that negative results are not as interesting to publish and therefore they get lower priority, and they get published later and sometimes not at all.”
Experts stressed that the problem is not confined to Nordic countries and that wasted medical research persists elsewhere in Europe and remains a global problem. For instance, a report published in the Journal of Clinical Epidemiology found that 30% of German trials completed between 2014 and 2017 remained unpublished 5 years after completion.
The Case for Laws, Monitoring, and Fines
Till Bruckner, PHD, from TranspariMED, which campaigns to end evidence distortion in medicine, told this news organization: “What is needed to comprehensively fix the problem is a national legal requirement to make all trial results public, coupled with effective monitoring, and followed by sanctions in the rare cases where institutions refuse to comply.”
Dr. Nilsonne added: “We have argued that the sponsors need to take greater responsibility, but also that there needs to be somebody whose job it is to monitor clinical trials reporting. It shouldn’t have to be that we do this as researchers on a shoestring with no dedicated resources. It should be somebody’s job.”
Since January 31, 2023, all initial clinical trial applications in the European Union must be submitted through the EU Clinical Trials Information System. Dr. Bruckner said that “the picture is not yet clear” in Europe, as the first trial results under the system are not expected until later this year. Even then, enforcement lies with regulators in individual countries. And while Denmark has already indicated it will enforce the regulations, he warned that other countries “might turn a blind eye.”
He pointed out that existing laws don’t apply to all types of trials. “That means that for many trials, nobody is legally responsible for ensuring that results are made public, and no government agency has any oversight or mandate,” he said.
Outside the EU, the United Kingdom has helped lead the way through the NHS Health Research Authority (HRA), which registers trials run in the country. One year after a trial has been completed, the HRA checks to see if the results have been uploaded to the registry and issues reminders if they haven’t.
In an update of its work in January, the authority said that compliance had hovered at just below 90% between 2018 and 2021 but that it was working to increase this to 100% by working with stakeholders across the research sector.
Dr. Nilsonne considers the UK system of central registration and follow-up an attractive option. “I would love to see something along those lines in other countries too,” he said.
‘Rampant Noncompliance’ in the United States
In the United States, a requirement to make trial results public is backed by law. Despite this, there’s evidence of “rampant noncompliance” and minimal government action, according to Megan Curtin from Universities Allied for Essential Medicines (UAEM), which has been tracking the issue in the United States and working to push universities and others to make their findings available.
The US Food and Drug Administration (FDA) shares responsibility with the National Institutes of Health for enforcement of clinical trial results reporting, but the UAEM says nearly 4000 trials are currently out of compliance with reporting requirements. In January last year, the UAEM copublished a report with the National Center for Health Research and TranspariMED, which found that 3627 American children participated in clinical trials whose results remain unreported.
The FDA can levy a fine of up to $10,000 USD for a violation of the law, but UAEM said that, as of January 2023, the FDA had sent only 92 preliminary notices of noncompliance and four notices of noncompliance. “A clear difference between the EU field of clinical trial operation and US clinical trials is that there are clear laws for reporting within 12 months, which can be enforced, but they’re not being enforced by the FDA,” Ms. Curtin told this news organization.
The UAEM is pushing the FDA to issue a minimum of 250 preliminary notices of noncompliance each year to noncompliant trial sponsors.
Dr. Nilsonne said: “I do believe we have a great responsibility to the patients that do contribute. We need to make sure that the harms and risks that a clinical trial entails are really balanced by knowledge gain, and if the results are never reported, then we can’t have a knowledge gain.”
A version of this article appeared on Medscape.com.
Shopping voucher incentives ‘doubles smoking quit rate in pregnancy’
Offering shopping vouchers to pregnant women as an incentive to quit smoking showed promising results, a study found, despite most participants relapsing after giving birth.
Rewarding pregnant women with up to £400 to spend on Main Street, in addition to usual support, more than doubled the proportion who were still smoke-free late in their pregnancy, and could save the National Health Service money in the long term, according to the research, published in the BMJ, led by the University of Glasgow and the University of York, England.
Although the proportion of women in the United Kingdom who smoke during pregnancy has halved over the past 20 years, those who still do are more reluctant to engage with cessation services.
Interventions using financial incentives were pioneered in the United States, but there is a lack of evidence for how effective they might be in the United Kingdom.
Vouchers linked to passing saliva tests
The phase 3 Cessation in Pregnancy Incentives Trial was based on an earlier feasibility study in Glasgow and involved 941 pregnant women aged 16 or older, with a mean age of 27.9 years when they were recruited, from seven stop-smoking services in Scotland, Northern Ireland, and England between January 2018 and April 2020. Participants self-reported that they smoked at least one cigarette a week.
The cohort was randomised into two groups: a control group who received usual stop smoking support that included the offer of counselling by trained workers combined with free nicotine-replacement therapy, and an intervention group who were given the same interventional support plus targets to receive LoveToShop vouchers.
Although vouchers to the value of £400 were on offer, earning them depended on successfully reaching four milestones. They received a first £50 voucher for engaging with stop-smoking services and setting a quit date and further vouchers for being declared smoke-free by biochemical verification at specific time points in the pregnancy.
Factors including the mother’s age, years of smoking, income, use of nicotine-replacement therapy and e-cigarettes, timing of birth, and birth weight were taken into account.
The study found that 71% of the participants in the incentive group engaged with stop-smoking services and set a quit date, compared with 64% in the control group. By late pregnancy, 126 participants (27%) of the 471 in the intervention group were smoke-free, compared with 58 (12%) of the 470 in the control group.
Most women in the trial went back to smoking
However, abstinence rates measured 6 months after giving birth were low in both groups: 6% in the intervention group vs. 4% in the control group.
The researchers also reported no significant differences in birth weight between the two groups.
Overall, the birth weight of babies from 443 intervention participants and 450 controls showed no significant difference between groups (average 3.18 kg vs. 3.13 kg).
The researchers did find a clinically important but not significant 10% increase in birth weight in the subset of participants who adhered with their treatment allocation, but they said further analysis is needed to better understand the relevance of this finding.
Severity of preterm birth was similar between groups, and all serious adverse events, such as miscarriages and stillbirths, were considered unrelated to the intervention.
The researchers acknowledged some limitations to their investigation, including that only 23% of women screened by stop-smoking services were enrolled, and that almost all participants were White. Also, the onset of COVID-19 disrupted some of the trial processes.
However, they concluded that their trial “supports implementation advocated in NICE [National Institute for Health and Care Excellence] guidelines by showing an effective, cost-effective, and generalisable pragmatic bolt-on U.K. format for incentive payments” to reduce smoking rates in pregnancy.
In a linked editorial, Daniel Kotz from the Heinrich Heine University, Düsseldorf, Germany, and Jasper Been from University Medical Center, Rotterdam, the Netherlands, pointed out that “partners of most pregnant women who smoke are also smokers,” which needed to be addressed. However, they wrote: “The medical community now has good evidence supporting effective tools, such as financial incentives, to reduce the health burden associated with tobacco smoking during pregnancy. These tools should be implemented wherever possible to protect and improve the health of women, their children, and their families.”
The trial was funded by Cancer Research UK; Chief Scientist Office, Scottish Government; HSC Public Health Agency Northern Ireland; Health and Social Care R&D Division NI Opportunity-Led Research Award; Chest Heart and Stroke Northern Ireland; Scottish Cot Death Trust; and Lullaby Trust 272. The authors declare no competing interests.
A version of this article first appeared on MedscapeUK.
Offering shopping vouchers to pregnant women as an incentive to quit smoking showed promising results, a study found, despite most participants relapsing after giving birth.
Rewarding pregnant women with up to £400 to spend on Main Street, in addition to usual support, more than doubled the proportion who were still smoke-free late in their pregnancy, and could save the National Health Service money in the long term, according to the research, published in the BMJ, led by the University of Glasgow and the University of York, England.
Although the proportion of women in the United Kingdom who smoke during pregnancy has halved over the past 20 years, those who still do are more reluctant to engage with cessation services.
Interventions using financial incentives were pioneered in the United States, but there is a lack of evidence for how effective they might be in the United Kingdom.
Vouchers linked to passing saliva tests
The phase 3 Cessation in Pregnancy Incentives Trial was based on an earlier feasibility study in Glasgow and involved 941 pregnant women aged 16 or older, with a mean age of 27.9 years when they were recruited, from seven stop-smoking services in Scotland, Northern Ireland, and England between January 2018 and April 2020. Participants self-reported that they smoked at least one cigarette a week.
The cohort was randomised into two groups: a control group who received usual stop smoking support that included the offer of counselling by trained workers combined with free nicotine-replacement therapy, and an intervention group who were given the same interventional support plus targets to receive LoveToShop vouchers.
Although vouchers to the value of £400 were on offer, earning them depended on successfully reaching four milestones. They received a first £50 voucher for engaging with stop-smoking services and setting a quit date and further vouchers for being declared smoke-free by biochemical verification at specific time points in the pregnancy.
Factors including the mother’s age, years of smoking, income, use of nicotine-replacement therapy and e-cigarettes, timing of birth, and birth weight were taken into account.
The study found that 71% of the participants in the incentive group engaged with stop-smoking services and set a quit date, compared with 64% in the control group. By late pregnancy, 126 participants (27%) of the 471 in the intervention group were smoke-free, compared with 58 (12%) of the 470 in the control group.
Most women in the trial went back to smoking
However, abstinence rates measured 6 months after giving birth were low in both groups: 6% in the intervention group vs. 4% in the control group.
The researchers also reported no significant differences in birth weight between the two groups.
Overall, the birth weight of babies from 443 intervention participants and 450 controls showed no significant difference between groups (average 3.18 kg vs. 3.13 kg).
The researchers did find a clinically important but not significant 10% increase in birth weight in the subset of participants who adhered with their treatment allocation, but they said further analysis is needed to better understand the relevance of this finding.
Severity of preterm birth was similar between groups, and all serious adverse events, such as miscarriages and stillbirths, were considered unrelated to the intervention.
The researchers acknowledged some limitations to their investigation, including that only 23% of women screened by stop-smoking services were enrolled, and that almost all participants were White. Also, the onset of COVID-19 disrupted some of the trial processes.
However, they concluded that their trial “supports implementation advocated in NICE [National Institute for Health and Care Excellence] guidelines by showing an effective, cost-effective, and generalisable pragmatic bolt-on U.K. format for incentive payments” to reduce smoking rates in pregnancy.
In a linked editorial, Daniel Kotz from the Heinrich Heine University, Düsseldorf, Germany, and Jasper Been from University Medical Center, Rotterdam, the Netherlands, pointed out that “partners of most pregnant women who smoke are also smokers,” which needed to be addressed. However, they wrote: “The medical community now has good evidence supporting effective tools, such as financial incentives, to reduce the health burden associated with tobacco smoking during pregnancy. These tools should be implemented wherever possible to protect and improve the health of women, their children, and their families.”
The trial was funded by Cancer Research UK; Chief Scientist Office, Scottish Government; HSC Public Health Agency Northern Ireland; Health and Social Care R&D Division NI Opportunity-Led Research Award; Chest Heart and Stroke Northern Ireland; Scottish Cot Death Trust; and Lullaby Trust 272. The authors declare no competing interests.
A version of this article first appeared on MedscapeUK.
Offering shopping vouchers to pregnant women as an incentive to quit smoking showed promising results, a study found, despite most participants relapsing after giving birth.
Rewarding pregnant women with up to £400 to spend on Main Street, in addition to usual support, more than doubled the proportion who were still smoke-free late in their pregnancy, and could save the National Health Service money in the long term, according to the research, published in the BMJ, led by the University of Glasgow and the University of York, England.
Although the proportion of women in the United Kingdom who smoke during pregnancy has halved over the past 20 years, those who still do are more reluctant to engage with cessation services.
Interventions using financial incentives were pioneered in the United States, but there is a lack of evidence for how effective they might be in the United Kingdom.
Vouchers linked to passing saliva tests
The phase 3 Cessation in Pregnancy Incentives Trial was based on an earlier feasibility study in Glasgow and involved 941 pregnant women aged 16 or older, with a mean age of 27.9 years when they were recruited, from seven stop-smoking services in Scotland, Northern Ireland, and England between January 2018 and April 2020. Participants self-reported that they smoked at least one cigarette a week.
The cohort was randomised into two groups: a control group who received usual stop smoking support that included the offer of counselling by trained workers combined with free nicotine-replacement therapy, and an intervention group who were given the same interventional support plus targets to receive LoveToShop vouchers.
Although vouchers to the value of £400 were on offer, earning them depended on successfully reaching four milestones. They received a first £50 voucher for engaging with stop-smoking services and setting a quit date and further vouchers for being declared smoke-free by biochemical verification at specific time points in the pregnancy.
Factors including the mother’s age, years of smoking, income, use of nicotine-replacement therapy and e-cigarettes, timing of birth, and birth weight were taken into account.
The study found that 71% of the participants in the incentive group engaged with stop-smoking services and set a quit date, compared with 64% in the control group. By late pregnancy, 126 participants (27%) of the 471 in the intervention group were smoke-free, compared with 58 (12%) of the 470 in the control group.
Most women in the trial went back to smoking
However, abstinence rates measured 6 months after giving birth were low in both groups: 6% in the intervention group vs. 4% in the control group.
The researchers also reported no significant differences in birth weight between the two groups.
Overall, the birth weight of babies from 443 intervention participants and 450 controls showed no significant difference between groups (average 3.18 kg vs. 3.13 kg).
The researchers did find a clinically important but not significant 10% increase in birth weight in the subset of participants who adhered with their treatment allocation, but they said further analysis is needed to better understand the relevance of this finding.
Severity of preterm birth was similar between groups, and all serious adverse events, such as miscarriages and stillbirths, were considered unrelated to the intervention.
The researchers acknowledged some limitations to their investigation, including that only 23% of women screened by stop-smoking services were enrolled, and that almost all participants were White. Also, the onset of COVID-19 disrupted some of the trial processes.
However, they concluded that their trial “supports implementation advocated in NICE [National Institute for Health and Care Excellence] guidelines by showing an effective, cost-effective, and generalisable pragmatic bolt-on U.K. format for incentive payments” to reduce smoking rates in pregnancy.
In a linked editorial, Daniel Kotz from the Heinrich Heine University, Düsseldorf, Germany, and Jasper Been from University Medical Center, Rotterdam, the Netherlands, pointed out that “partners of most pregnant women who smoke are also smokers,” which needed to be addressed. However, they wrote: “The medical community now has good evidence supporting effective tools, such as financial incentives, to reduce the health burden associated with tobacco smoking during pregnancy. These tools should be implemented wherever possible to protect and improve the health of women, their children, and their families.”
The trial was funded by Cancer Research UK; Chief Scientist Office, Scottish Government; HSC Public Health Agency Northern Ireland; Health and Social Care R&D Division NI Opportunity-Led Research Award; Chest Heart and Stroke Northern Ireland; Scottish Cot Death Trust; and Lullaby Trust 272. The authors declare no competing interests.
A version of this article first appeared on MedscapeUK.
FROM BMJ
Birth weight below 25th percentile linked to child development problems
Babies born from the 37th week of pregnancy who are mild to moderately small for gestational age (SGA) could benefit from monitoring to check for developmental problems, a study suggested.
A team of researchers at Coventry (England) University found that birth weight below the 25th percentile was associated with more developmental concerns in early childhood than a weight between the 25th and 74th percentile.
Those difficulties were apparent at percentiles higher than the conventional threshold defining SGA, they noted.
Low and high extremes of birth weight have been associated with adverse pregnancy and neonatal health outcomes, but little is known about the effects on motor skills, socialization, language, and other developmental markers for the entire range of birth weights for nonpremature babies.
Study linked health databases to child assessment results
To find out more, researchers conducted a population-based cohort study of 686,284 singleton infants born from 37 weeks of gestation, linking pregnancy and birth records from health databases covering all of Scotland to child development assessments carried out between the ages of 2 and 3.5 years.
The researchers looked for associations between birth weight and early childhood developmental concerns, taking into account confounders, such as maternal age, the mother’s medical history during pregnancy, early pregnancy body mass index, deprivation, ethnicity, alcohol use, and smoking history.
The study, published in the open access journal PLOS Medicine, found that babies born below the 25th percentile for birth weight had a higher risk of developmental concerns, compared with babies born between the 25th and 74th percentiles, with the infants who had the lowest birth weight most at risk of later developmental difficulties.
Those born between the 10th and 24th percentile had a relative risk of 1.07 (95% confidence interval, 1.03-1.12; P < .001); between the 3rd and 9th percentile, the RR was 1.18 (95% CI, 1.12-1.25, P < .001), and below the 3rd percentile the RR was 1.37 (95% CI, 1.24-1.50; P < .001).
No substantial increase in the risk of early childhood developmental concerns was identified for larger birth weight categories in the 75th-89th percentile range, the researchers reported.
Monitoring and support
The researchers concluded that having mild to moderate SGA “is an unrecognized, potentially important contributor to the prevalence of developmental concerns.”
Before this study, babies below the 10th percentile were usually considered at risk for developmental concerns. However, the investigation found a greater number of babies within the 10th-24th percentile range of birth weights with these issues, simply because there were a larger number of babies within that population.
Abiodun Adanikin, MBBS, PhD, MPH, of Coventry University’s Centre for Healthcare Research, and study first author, said: “Though it is mostly unrecognized, babies who are mild to moderately small at birth are key contributors to the burden of childhood developmental concerns. They may need closer monitoring and increased support to reduce the risk of developmental concerns.”
The study also involved colleagues from the University of Bristol (England), the University of Glasgow, the University of Cambridge (England), and Queen Mary University of London.
This work was supported by a Wellbeing of Women Research Grant. One author has received research support from Roche Diagnostics, GSK, Illumina, and Sera Prognostics (fetal growth restriction, preeclampsia and preterm birth). He has been a paid consultant to GSK (preterm birth) and is a member of a Data Monitoring Committee for GSK trials of RSV vaccination in pregnancy. He is one of three named inventors on a patent application filed by Cambridge Enterprise for novel predictive test for fetal growth disorder. He is an academic editor on PLOS Medicine’s editorial board. The authors declare no other competing interest.
A version of this article first appeared on Medscape UK.
Babies born from the 37th week of pregnancy who are mild to moderately small for gestational age (SGA) could benefit from monitoring to check for developmental problems, a study suggested.
A team of researchers at Coventry (England) University found that birth weight below the 25th percentile was associated with more developmental concerns in early childhood than a weight between the 25th and 74th percentile.
Those difficulties were apparent at percentiles higher than the conventional threshold defining SGA, they noted.
Low and high extremes of birth weight have been associated with adverse pregnancy and neonatal health outcomes, but little is known about the effects on motor skills, socialization, language, and other developmental markers for the entire range of birth weights for nonpremature babies.
Study linked health databases to child assessment results
To find out more, researchers conducted a population-based cohort study of 686,284 singleton infants born from 37 weeks of gestation, linking pregnancy and birth records from health databases covering all of Scotland to child development assessments carried out between the ages of 2 and 3.5 years.
The researchers looked for associations between birth weight and early childhood developmental concerns, taking into account confounders, such as maternal age, the mother’s medical history during pregnancy, early pregnancy body mass index, deprivation, ethnicity, alcohol use, and smoking history.
The study, published in the open access journal PLOS Medicine, found that babies born below the 25th percentile for birth weight had a higher risk of developmental concerns, compared with babies born between the 25th and 74th percentiles, with the infants who had the lowest birth weight most at risk of later developmental difficulties.
Those born between the 10th and 24th percentile had a relative risk of 1.07 (95% confidence interval, 1.03-1.12; P < .001); between the 3rd and 9th percentile, the RR was 1.18 (95% CI, 1.12-1.25, P < .001), and below the 3rd percentile the RR was 1.37 (95% CI, 1.24-1.50; P < .001).
No substantial increase in the risk of early childhood developmental concerns was identified for larger birth weight categories in the 75th-89th percentile range, the researchers reported.
Monitoring and support
The researchers concluded that having mild to moderate SGA “is an unrecognized, potentially important contributor to the prevalence of developmental concerns.”
Before this study, babies below the 10th percentile were usually considered at risk for developmental concerns. However, the investigation found a greater number of babies within the 10th-24th percentile range of birth weights with these issues, simply because there were a larger number of babies within that population.
Abiodun Adanikin, MBBS, PhD, MPH, of Coventry University’s Centre for Healthcare Research, and study first author, said: “Though it is mostly unrecognized, babies who are mild to moderately small at birth are key contributors to the burden of childhood developmental concerns. They may need closer monitoring and increased support to reduce the risk of developmental concerns.”
The study also involved colleagues from the University of Bristol (England), the University of Glasgow, the University of Cambridge (England), and Queen Mary University of London.
This work was supported by a Wellbeing of Women Research Grant. One author has received research support from Roche Diagnostics, GSK, Illumina, and Sera Prognostics (fetal growth restriction, preeclampsia and preterm birth). He has been a paid consultant to GSK (preterm birth) and is a member of a Data Monitoring Committee for GSK trials of RSV vaccination in pregnancy. He is one of three named inventors on a patent application filed by Cambridge Enterprise for novel predictive test for fetal growth disorder. He is an academic editor on PLOS Medicine’s editorial board. The authors declare no other competing interest.
A version of this article first appeared on Medscape UK.
Babies born from the 37th week of pregnancy who are mild to moderately small for gestational age (SGA) could benefit from monitoring to check for developmental problems, a study suggested.
A team of researchers at Coventry (England) University found that birth weight below the 25th percentile was associated with more developmental concerns in early childhood than a weight between the 25th and 74th percentile.
Those difficulties were apparent at percentiles higher than the conventional threshold defining SGA, they noted.
Low and high extremes of birth weight have been associated with adverse pregnancy and neonatal health outcomes, but little is known about the effects on motor skills, socialization, language, and other developmental markers for the entire range of birth weights for nonpremature babies.
Study linked health databases to child assessment results
To find out more, researchers conducted a population-based cohort study of 686,284 singleton infants born from 37 weeks of gestation, linking pregnancy and birth records from health databases covering all of Scotland to child development assessments carried out between the ages of 2 and 3.5 years.
The researchers looked for associations between birth weight and early childhood developmental concerns, taking into account confounders, such as maternal age, the mother’s medical history during pregnancy, early pregnancy body mass index, deprivation, ethnicity, alcohol use, and smoking history.
The study, published in the open access journal PLOS Medicine, found that babies born below the 25th percentile for birth weight had a higher risk of developmental concerns, compared with babies born between the 25th and 74th percentiles, with the infants who had the lowest birth weight most at risk of later developmental difficulties.
Those born between the 10th and 24th percentile had a relative risk of 1.07 (95% confidence interval, 1.03-1.12; P < .001); between the 3rd and 9th percentile, the RR was 1.18 (95% CI, 1.12-1.25, P < .001), and below the 3rd percentile the RR was 1.37 (95% CI, 1.24-1.50; P < .001).
No substantial increase in the risk of early childhood developmental concerns was identified for larger birth weight categories in the 75th-89th percentile range, the researchers reported.
Monitoring and support
The researchers concluded that having mild to moderate SGA “is an unrecognized, potentially important contributor to the prevalence of developmental concerns.”
Before this study, babies below the 10th percentile were usually considered at risk for developmental concerns. However, the investigation found a greater number of babies within the 10th-24th percentile range of birth weights with these issues, simply because there were a larger number of babies within that population.
Abiodun Adanikin, MBBS, PhD, MPH, of Coventry University’s Centre for Healthcare Research, and study first author, said: “Though it is mostly unrecognized, babies who are mild to moderately small at birth are key contributors to the burden of childhood developmental concerns. They may need closer monitoring and increased support to reduce the risk of developmental concerns.”
The study also involved colleagues from the University of Bristol (England), the University of Glasgow, the University of Cambridge (England), and Queen Mary University of London.
This work was supported by a Wellbeing of Women Research Grant. One author has received research support from Roche Diagnostics, GSK, Illumina, and Sera Prognostics (fetal growth restriction, preeclampsia and preterm birth). He has been a paid consultant to GSK (preterm birth) and is a member of a Data Monitoring Committee for GSK trials of RSV vaccination in pregnancy. He is one of three named inventors on a patent application filed by Cambridge Enterprise for novel predictive test for fetal growth disorder. He is an academic editor on PLOS Medicine’s editorial board. The authors declare no other competing interest.
A version of this article first appeared on Medscape UK.
FROM PLOS MEDICINE
Taking the heat out of coffee’s esophageal cancer risk
Whether coffee is good or bad for health is a frequent debate in the media, fueled by apparently conflicting studies suggesting the plethora of bioactive chemicals in the popular brew could either raise or lower cancer risk.
Now, an analysis by Cambridge scientists has suggested that while coffee is not associated with enhanced overall risk of non–digestive system cancers among people genetically predicted to drink more of it, 
, although this might be explained by a tendency for drinking it warm or hot, the study in the journal Clinical Nutrition suggested.
Regular coffee drinking has been linked to a slightly lower risk of all-cause mortality. However, it remains unclear whether coffee consumption is associated with a lower risk of dying from cancer.
Hotly debated
In 2016, a working group of international scientists convened by the International Agency for Research on Cancer (IARC) found no conclusive evidence for a carcinogenic effect of drinking coffee. However, the experts did find that drinking very hot beverages was a probable cause of esophageal cancer, making “the temperature, rather than the drinks themselves” the most likely cause, according to the organization’s director.
This latest study concurred. “We provide strong evidence for a causal relationship which is large in magnitude (threefold) and consistent across sensitivity analyses and in a replication study,” it stated.
The Cambridge researchers, assisted by colleagues at the Karolinska Institutet in Stockholm and Bristol Medical School, conducted a Mendelian randomization study to investigate causal associations between coffee consumption and 22 site-specific cancers using data of individuals of European descent in the UK Biobank.
They reported “no strong evidence supporting a causal relationship between genetically-predicted coffee consumption and the majority of cancers studied” (odds ratio [OR], in the main analysis 1.05, 95% confidence interval [CI], 0.98-1.14, P = .183), and remained without association after adjustments for predicted BMI, smoking, or alcohol consumption.
However, genetically predicted coffee consumption was linked to an increased risk of digestive system cancer (OR, 1.28, 95% CI, 1.09-1.51, P = .003), and the risk was largely attributed to “a strong association with esophageal cancer” (OR, 2.79, 95% CI, 1.73-4.50, P = 2.5x10-5). This risk association remained persistent after adjustment for confounders, the researchers said.
Coffee or tea?
Further analysis of the data found that increased risk of esophageal cancer was consistently associated with genetically predicted coffee consumption by individuals with a preference for warm and hot drinks. Among this group, a similar esophageal cancer risk profile among those who reported drinking one to three cups of coffee a day and those who said they did not drink coffee was most likely due to a high prevalence of tea drinking, the study authors said.
“It is, therefore, plausible that a carcinogenic effect of coffee relates to thermal injury broadly, rather than being specific to coffee or its constituents,” said the scientists, who highlighted that this was also pointed out by the IARC in its statement 6 years ago.
Genetically predicted coffee consumption was also found to be associated with increased risk of multiple myeloma (OR, 2.25, 95% CI, 1.30-3.89, P = .004) and reduced ovarian cancer risk (OR, 0.63, 95% CI, 0.43-0.93, P = .020).
The authors concluded there was “evidence for coffee consumption being causally associated with risk of esophageal cancer, with some evidence this is related to a temperature effect.” Otherwise, “our results do not support a linear causal association with the majority of cancer types studied, other than limited evidence for harmful and protective associations with multiple myeloma and ovarian cancers respectively.”
Further studies were needed to investigate “the possible mechanisms of coffee consumption in esophageal carcinogenesis,” they said.
A version of this article first appeared on Medscape UK.
Whether coffee is good or bad for health is a frequent debate in the media, fueled by apparently conflicting studies suggesting the plethora of bioactive chemicals in the popular brew could either raise or lower cancer risk.
Now, an analysis by Cambridge scientists has suggested that while coffee is not associated with enhanced overall risk of non–digestive system cancers among people genetically predicted to drink more of it,
, although this might be explained by a tendency for drinking it warm or hot, the study in the journal Clinical Nutrition suggested.
Regular coffee drinking has been linked to a slightly lower risk of all-cause mortality. However, it remains unclear whether coffee consumption is associated with a lower risk of dying from cancer.
Hotly debated
In 2016, a working group of international scientists convened by the International Agency for Research on Cancer (IARC) found no conclusive evidence for a carcinogenic effect of drinking coffee. However, the experts did find that drinking very hot beverages was a probable cause of esophageal cancer, making “the temperature, rather than the drinks themselves” the most likely cause, according to the organization’s director.
This latest study concurred. “We provide strong evidence for a causal relationship which is large in magnitude (threefold) and consistent across sensitivity analyses and in a replication study,” it stated.
The Cambridge researchers, assisted by colleagues at the Karolinska Institutet in Stockholm and Bristol Medical School, conducted a Mendelian randomization study to investigate causal associations between coffee consumption and 22 site-specific cancers using data of individuals of European descent in the UK Biobank.
They reported “no strong evidence supporting a causal relationship between genetically-predicted coffee consumption and the majority of cancers studied” (odds ratio [OR], in the main analysis 1.05, 95% confidence interval [CI], 0.98-1.14, P = .183), and remained without association after adjustments for predicted BMI, smoking, or alcohol consumption.
However, genetically predicted coffee consumption was linked to an increased risk of digestive system cancer (OR, 1.28, 95% CI, 1.09-1.51, P = .003), and the risk was largely attributed to “a strong association with esophageal cancer” (OR, 2.79, 95% CI, 1.73-4.50, P = 2.5x10-5). This risk association remained persistent after adjustment for confounders, the researchers said.
Coffee or tea?
Further analysis of the data found that increased risk of esophageal cancer was consistently associated with genetically predicted coffee consumption by individuals with a preference for warm and hot drinks. Among this group, a similar esophageal cancer risk profile among those who reported drinking one to three cups of coffee a day and those who said they did not drink coffee was most likely due to a high prevalence of tea drinking, the study authors said.
“It is, therefore, plausible that a carcinogenic effect of coffee relates to thermal injury broadly, rather than being specific to coffee or its constituents,” said the scientists, who highlighted that this was also pointed out by the IARC in its statement 6 years ago.
Genetically predicted coffee consumption was also found to be associated with increased risk of multiple myeloma (OR, 2.25, 95% CI, 1.30-3.89, P = .004) and reduced ovarian cancer risk (OR, 0.63, 95% CI, 0.43-0.93, P = .020).
The authors concluded there was “evidence for coffee consumption being causally associated with risk of esophageal cancer, with some evidence this is related to a temperature effect.” Otherwise, “our results do not support a linear causal association with the majority of cancer types studied, other than limited evidence for harmful and protective associations with multiple myeloma and ovarian cancers respectively.”
Further studies were needed to investigate “the possible mechanisms of coffee consumption in esophageal carcinogenesis,” they said.
A version of this article first appeared on Medscape UK.
Whether coffee is good or bad for health is a frequent debate in the media, fueled by apparently conflicting studies suggesting the plethora of bioactive chemicals in the popular brew could either raise or lower cancer risk.
Now, an analysis by Cambridge scientists has suggested that while coffee is not associated with enhanced overall risk of non–digestive system cancers among people genetically predicted to drink more of it,
, although this might be explained by a tendency for drinking it warm or hot, the study in the journal Clinical Nutrition suggested.
Regular coffee drinking has been linked to a slightly lower risk of all-cause mortality. However, it remains unclear whether coffee consumption is associated with a lower risk of dying from cancer.
Hotly debated
In 2016, a working group of international scientists convened by the International Agency for Research on Cancer (IARC) found no conclusive evidence for a carcinogenic effect of drinking coffee. However, the experts did find that drinking very hot beverages was a probable cause of esophageal cancer, making “the temperature, rather than the drinks themselves” the most likely cause, according to the organization’s director.
This latest study concurred. “We provide strong evidence for a causal relationship which is large in magnitude (threefold) and consistent across sensitivity analyses and in a replication study,” it stated.
The Cambridge researchers, assisted by colleagues at the Karolinska Institutet in Stockholm and Bristol Medical School, conducted a Mendelian randomization study to investigate causal associations between coffee consumption and 22 site-specific cancers using data of individuals of European descent in the UK Biobank.
They reported “no strong evidence supporting a causal relationship between genetically-predicted coffee consumption and the majority of cancers studied” (odds ratio [OR], in the main analysis 1.05, 95% confidence interval [CI], 0.98-1.14, P = .183), and remained without association after adjustments for predicted BMI, smoking, or alcohol consumption.
However, genetically predicted coffee consumption was linked to an increased risk of digestive system cancer (OR, 1.28, 95% CI, 1.09-1.51, P = .003), and the risk was largely attributed to “a strong association with esophageal cancer” (OR, 2.79, 95% CI, 1.73-4.50, P = 2.5x10-5). This risk association remained persistent after adjustment for confounders, the researchers said.
Coffee or tea?
Further analysis of the data found that increased risk of esophageal cancer was consistently associated with genetically predicted coffee consumption by individuals with a preference for warm and hot drinks. Among this group, a similar esophageal cancer risk profile among those who reported drinking one to three cups of coffee a day and those who said they did not drink coffee was most likely due to a high prevalence of tea drinking, the study authors said.
“It is, therefore, plausible that a carcinogenic effect of coffee relates to thermal injury broadly, rather than being specific to coffee or its constituents,” said the scientists, who highlighted that this was also pointed out by the IARC in its statement 6 years ago.
Genetically predicted coffee consumption was also found to be associated with increased risk of multiple myeloma (OR, 2.25, 95% CI, 1.30-3.89, P = .004) and reduced ovarian cancer risk (OR, 0.63, 95% CI, 0.43-0.93, P = .020).
The authors concluded there was “evidence for coffee consumption being causally associated with risk of esophageal cancer, with some evidence this is related to a temperature effect.” Otherwise, “our results do not support a linear causal association with the majority of cancer types studied, other than limited evidence for harmful and protective associations with multiple myeloma and ovarian cancers respectively.”
Further studies were needed to investigate “the possible mechanisms of coffee consumption in esophageal carcinogenesis,” they said.
A version of this article first appeared on Medscape UK.
FROM CLINICAL NUTRITION
Mother’s fat metabolism in early pregnancy linked to baby’s weight
A baby’s weight and neurodevelopment in the first 2 years of life could be influenced by maternal fat metabolism in the early stages of pregnancy, according to a study.
Patterns of fetal abdominal growth were associated with maternal lipid metabolites that tracked newborn growth, adiposity, and development into childhood and could be identified as early as the 5th month of pregnancy, according to researchers at the University of Oxford, working with colleagues at the University of California.
These fetal growth patterns were also associated with blood flow and nutrient transfer by the placenta, demonstrating a complex interaction between maternal and fetal nutrition early in pregnancy, with implications for postnatal weight and health in later life, they suggested.
Stephen Kennedy, MD, professor of reproductive medicine at the University of Oxford, who co-led the investigation, said it had “provided valuable new insights into the biological origins of childhood obesity, which is one of the most pressing public health issues facing governments around the world.”
International study
The prospective observational study, published in The Lancet Diabetes and Endocrinology, involved 3,598 pregnant women from six countries – Brazil, Kenya, Pakistan, South Africa, Thailand, and the United Kingdom – aged 18 and older and with a BMI of less than 35 kg/m2. The women were monitored using regular fetal ultrasound scans and metabolomic analysis of early pregnancy maternal blood and umbilical cord venous blood at the time of birth.
Their infants, who were singletons, and conceived naturally, were then followed for 2 years to assess their growth and development.
Fetal abdominal circumference growth was found to accelerate or decelerate within “a crucial 20-25 week gestational age window” that followed 4 trajectories of faltering growth, early accelerating growth, late accelerating growth, or median growth. These traits were matched by fetus-placenta blood flow patterns throughout pregnancy and different growth, adiposity, vision, and neurodevelopment outcomes in early childhood, researchers said.
Overall, 709 maternal metabolites had a positive effect for the faltering growth phenotype, and 54 for the early accelerating growth phenotype, whilst 31 had a negative effect for the faltering growth phenotype and 76 for the early accelerating growth phenotype.
The maternal metabolite signatures included 5-hydroxy-eicosatetraenoic acid and 11 phosphatidylcholines linked to oxylipin or saturated fatty acid sidechains. The fungicide, chlorothalonil, was “highly abundant” in the early accelerating growth phenotype group.
‘A unique insight’
Aris Papageorghiou, professor of Fetal Medicine at the University of Oxford, who co-led the research, said: “This study provides evidence of distinct patterns of fetal abdominal growth and placental transfer and how they relate to longer term health. The finding of an association with maternal lipid metabolism early in pregnancy also provides unique insights into how the mother’s health and diet influence her child’s adiposity.”
First author José Villar, MD, professor of perinatal medicine at Oxford, said: “The study complements our previous work that identified fetal head growth trajectories associated with different developmental, behavioral, visual, and growth outcomes at 2 years of age.” Taken together, “the growth of babies’ bodies and brain[s] track separately and early – while still within the womb,” he said.
According to Dr. Kennedy, the latest results “could contribute to earlier identification of infants at risk of obesity” and urged policymakers to “take notice of these findings in their efforts to prevent the oncoming epidemic of obesity, with all its likely adverse social and economic consequences.”
Funding for the study was provided by the Bill and Melinda Gates Foundation.
A version of this article first appeared on Medscape UK.
A baby’s weight and neurodevelopment in the first 2 years of life could be influenced by maternal fat metabolism in the early stages of pregnancy, according to a study.
Patterns of fetal abdominal growth were associated with maternal lipid metabolites that tracked newborn growth, adiposity, and development into childhood and could be identified as early as the 5th month of pregnancy, according to researchers at the University of Oxford, working with colleagues at the University of California.
These fetal growth patterns were also associated with blood flow and nutrient transfer by the placenta, demonstrating a complex interaction between maternal and fetal nutrition early in pregnancy, with implications for postnatal weight and health in later life, they suggested.
Stephen Kennedy, MD, professor of reproductive medicine at the University of Oxford, who co-led the investigation, said it had “provided valuable new insights into the biological origins of childhood obesity, which is one of the most pressing public health issues facing governments around the world.”
International study
The prospective observational study, published in The Lancet Diabetes and Endocrinology, involved 3,598 pregnant women from six countries – Brazil, Kenya, Pakistan, South Africa, Thailand, and the United Kingdom – aged 18 and older and with a BMI of less than 35 kg/m2. The women were monitored using regular fetal ultrasound scans and metabolomic analysis of early pregnancy maternal blood and umbilical cord venous blood at the time of birth.
Their infants, who were singletons, and conceived naturally, were then followed for 2 years to assess their growth and development.
Fetal abdominal circumference growth was found to accelerate or decelerate within “a crucial 20-25 week gestational age window” that followed 4 trajectories of faltering growth, early accelerating growth, late accelerating growth, or median growth. These traits were matched by fetus-placenta blood flow patterns throughout pregnancy and different growth, adiposity, vision, and neurodevelopment outcomes in early childhood, researchers said.
Overall, 709 maternal metabolites had a positive effect for the faltering growth phenotype, and 54 for the early accelerating growth phenotype, whilst 31 had a negative effect for the faltering growth phenotype and 76 for the early accelerating growth phenotype.
The maternal metabolite signatures included 5-hydroxy-eicosatetraenoic acid and 11 phosphatidylcholines linked to oxylipin or saturated fatty acid sidechains. The fungicide, chlorothalonil, was “highly abundant” in the early accelerating growth phenotype group.
‘A unique insight’
Aris Papageorghiou, professor of Fetal Medicine at the University of Oxford, who co-led the research, said: “This study provides evidence of distinct patterns of fetal abdominal growth and placental transfer and how they relate to longer term health. The finding of an association with maternal lipid metabolism early in pregnancy also provides unique insights into how the mother’s health and diet influence her child’s adiposity.”
First author José Villar, MD, professor of perinatal medicine at Oxford, said: “The study complements our previous work that identified fetal head growth trajectories associated with different developmental, behavioral, visual, and growth outcomes at 2 years of age.” Taken together, “the growth of babies’ bodies and brain[s] track separately and early – while still within the womb,” he said.
According to Dr. Kennedy, the latest results “could contribute to earlier identification of infants at risk of obesity” and urged policymakers to “take notice of these findings in their efforts to prevent the oncoming epidemic of obesity, with all its likely adverse social and economic consequences.”
Funding for the study was provided by the Bill and Melinda Gates Foundation.
A version of this article first appeared on Medscape UK.
A baby’s weight and neurodevelopment in the first 2 years of life could be influenced by maternal fat metabolism in the early stages of pregnancy, according to a study.
Patterns of fetal abdominal growth were associated with maternal lipid metabolites that tracked newborn growth, adiposity, and development into childhood and could be identified as early as the 5th month of pregnancy, according to researchers at the University of Oxford, working with colleagues at the University of California.
These fetal growth patterns were also associated with blood flow and nutrient transfer by the placenta, demonstrating a complex interaction between maternal and fetal nutrition early in pregnancy, with implications for postnatal weight and health in later life, they suggested.
Stephen Kennedy, MD, professor of reproductive medicine at the University of Oxford, who co-led the investigation, said it had “provided valuable new insights into the biological origins of childhood obesity, which is one of the most pressing public health issues facing governments around the world.”
International study
The prospective observational study, published in The Lancet Diabetes and Endocrinology, involved 3,598 pregnant women from six countries – Brazil, Kenya, Pakistan, South Africa, Thailand, and the United Kingdom – aged 18 and older and with a BMI of less than 35 kg/m2. The women were monitored using regular fetal ultrasound scans and metabolomic analysis of early pregnancy maternal blood and umbilical cord venous blood at the time of birth.
Their infants, who were singletons, and conceived naturally, were then followed for 2 years to assess their growth and development.
Fetal abdominal circumference growth was found to accelerate or decelerate within “a crucial 20-25 week gestational age window” that followed 4 trajectories of faltering growth, early accelerating growth, late accelerating growth, or median growth. These traits were matched by fetus-placenta blood flow patterns throughout pregnancy and different growth, adiposity, vision, and neurodevelopment outcomes in early childhood, researchers said.
Overall, 709 maternal metabolites had a positive effect for the faltering growth phenotype, and 54 for the early accelerating growth phenotype, whilst 31 had a negative effect for the faltering growth phenotype and 76 for the early accelerating growth phenotype.
The maternal metabolite signatures included 5-hydroxy-eicosatetraenoic acid and 11 phosphatidylcholines linked to oxylipin or saturated fatty acid sidechains. The fungicide, chlorothalonil, was “highly abundant” in the early accelerating growth phenotype group.
‘A unique insight’
Aris Papageorghiou, professor of Fetal Medicine at the University of Oxford, who co-led the research, said: “This study provides evidence of distinct patterns of fetal abdominal growth and placental transfer and how they relate to longer term health. The finding of an association with maternal lipid metabolism early in pregnancy also provides unique insights into how the mother’s health and diet influence her child’s adiposity.”
First author José Villar, MD, professor of perinatal medicine at Oxford, said: “The study complements our previous work that identified fetal head growth trajectories associated with different developmental, behavioral, visual, and growth outcomes at 2 years of age.” Taken together, “the growth of babies’ bodies and brain[s] track separately and early – while still within the womb,” he said.
According to Dr. Kennedy, the latest results “could contribute to earlier identification of infants at risk of obesity” and urged policymakers to “take notice of these findings in their efforts to prevent the oncoming epidemic of obesity, with all its likely adverse social and economic consequences.”
Funding for the study was provided by the Bill and Melinda Gates Foundation.
A version of this article first appeared on Medscape UK.