Lead pollutants as harmful to health as particulate matter

Article Type
Changed
Mon, 10/09/2023 - 13:41

Lead is significantly more harmful to the health of children and adults across the world than previously thought. This conclusion is suggested by a modeling study presented by Norwegian development economist Bjorn Larsen and the Colombian environmental specialist for lead Ernesto Sánchez-Triana, PhD, in a presentation to the World Bank. Their work was published in The Lancet Planetary Health.

As Mr. Larsen and Mr. Sánchez-Triana report, the economic consequences of increased exposure to lead are already immense, especially in low- and middle-income countries (LMICs). The study was financed by the Korea Green Growth Trust Fund and the World Bank’s Pollution Management and Environmental Health Program.
 

Intellectual, cardiovascular effects

“It is a very important publication that affects all of us,” pediatrician Stephan Böse-O’Reilly, MD, of the Institute and Polyclinic for Occupational, Social, and Environmental Health at Ludwig Maximilian University Hospital in Munich, Germany, said in an interview. “The study, the results of which I think are very reliable, shows that elevated levels of lead in the blood have a much more drastic effect on children’s intelligence than we previously thought.”

It is well known that lead affects the antenatal and postnatal cognitive development of children, Dr. Böse-O’Reilly explained. But the extent of this effect has quite clearly been underestimated before now.

On the other hand, Mr. Larsen and Mr. Sánchez-Triana’s work could prove that lead may lead to more cardiovascular diseases in adulthood. “We already knew that increased exposure to lead increased the risk of high blood pressure and, as a result, mortality,” said Dr. Böse-O’Reilly. “This study now very clearly shows that the risk of arteriosclerosis, for example, also increases through lead exposure.”
 

Figures from 2019

“For the first time, to our knowledge, we aimed to estimate the global burden and cost of IQ loss and cardiovascular disease mortality from lead exposure,” wrote Mr. Larsen and Mr. Sánchez-Triana. For their calculations, the scientists used blood lead level estimates from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019.

They estimated IQ loss in children younger than 5 years using the internationally recognized blood lead level–IQ loss function. The researchers subsequently estimated the cost of this IQ loss based on the loss in lifetime income, presented as cost in U.S. dollars and percentage of gross domestic product (GDP).

Mr. Larsen and Mr. Sánchez-Triana estimated cardiovascular deaths caused by lead exposure in adults aged 25 years or older using a model that captures the effects of lead exposure on cardiovascular disease mortality that is mediated through mechanisms other than hypertension.

Finally, they used the statistical life expectancy to estimate the welfare cost of premature mortality, also presented as cost in U.S. dollars and percentage of GDP. All estimates were calculated according to the World Bank income classification for 2019.
 

Millions of deaths

As reported by Mr. Larsen and Mr. Sánchez-Triana, children younger than 5 years lost an estimated 765 million IQ points worldwide because of lead exposure in this period. In 2019, 5,545,000 adults died from cardiovascular diseases caused by lead exposure. The scientists recorded 729 million of the IQ points lost (95.3%) and 5,004,000 (90.2%) of the deaths as occurring in LMICs.

The IQ loss here was nearly 80% higher than a previous estimate, wrote Mr. Larsen and Mr. Sánchez-Triana. The number of cardiovascular disease deaths they determined was six times higher than the GBD 2019 estimate.



“These are results with which the expert societies, especially the German Society of Pediatrics and Adolescent Medicine and the German Cardiac Society, and the corresponding professional associations need to concern themselves,” said Dr. Böse-O’Reilly.

Although blood lead concentrations have declined substantially since the phase-out of leaded gasoline, especially in Western countries, lead still represents a major health issue because it stays in the bones for decades.

European situation moderate

“We need a broad discussion on questions such as whether lead levels should be included in prophylactic assessments in certain age groups, what blood level is even tolerable, and in what situation medicinal therapy with chelating agents would possibly be appropriate,” said Dr. Böse-O’Reilly.

“Of course, we cannot answer these questions on the basis of one individual study,” he added. “However, the work in question definitely illustrates how dangerous lead can be and that we need further research into the actual burden and the best preventive measures.”

In this respect, the situation in Europe is still comparatively moderate. “Globally, lead exposure has risen in recent years,” said Dr. Böse-O’Reilly. According to an investigation by the Planet Earth Foundation, outside of the European Union, lead can increasingly be found in toys, spices, and cooking utensils, for example.

“Especially in lower-income countries, there is a lack of consumer protection or a good monitoring program like we have here in the EU,” said Dr. Böse-O’Reilly. In these countries, lead is sometimes added to spices by unscrupulous retailers to make the color more intense or to simply add to its weight to gain more profit.

Recycling lead-acid batteries or other electrical waste, often transferred to poorer countries, constitutes a large problem. “In general, children in Germany have a blood lead level of less than 1 mcg/dL,” explained Dr. Böse-O’Reilly. “In some regions of Indonesia, where these recycling factories are located, more than 50% of children have levels of more than 20 mcg/dL.”
 

Particulate matter

According to Mr. Larsen and Mr. Sánchez-Triana, the global cost of increased lead exposure was around $6 trillion USD in 2019, which was equivalent to 6.9% of global GDP. About 77% of the cost ($4.62 trillion USD) comprised the welfare costs of cardiovascular disease mortality, and 23% ($1.38 trillion USD) comprised the present value of future income losses because of IQ loss in children.

“Our findings suggest that global lead exposure has health and economic costs on par with PM2.5 air pollution,” wrote the authors. This places lead as an environmental risk factor on par with particulate matter and above that of air pollution from solid fuels, ahead of unsafe drinking water, unhygienic sanitation, or insufficient handwashing.

“This finding is in contrast to that of GBD 2019, which ranked lead exposure as a distant fourth environmental risk factor, due to not accounting for IQ loss in children – other than idiopathic developmental intellectual disability in a small subset of children – and reporting a substantially lower estimate of adult cardiovascular disease mortality,” wrote Mr. Larsen and Mr. Sánchez-Triana.

“A central implication for future research and policy is that LMICs bear an extraordinarily large share of the health and cost burden of lead exposure,” wrote the authors. Consequently, improved quality of blood lead level measurements and identification of sources containing lead are urgently needed there.
 

Improved recycling methods

Dr. Böse-O’Reilly would like an increased focus on children. “If children’s cognitive skills are lost, this of course has a long-term effect on a country’s economic position,” he said. “Precisely that which LMICs actually need for their development is being stripped from them.

“We should think long and hard about whether we really need to send so much of our electrical waste and so many old cars to poorer countries, where they are incorrectly recycled,” he warned. “We should at least give the LMICs the support necessary for them to be able to process lead-containing products in the future so that less lead makes it into the environment.

“Through these global cycles, we all contribute a lot toward the worldwide lead burden,” Dr. Böse-O’Reilly said. “In my opinion, the German Supply Chain Act is therefore definitely sensible. Not only does it protect our own economy, but it also protects the health of people in other countries.”

This article was translated from Medscape’s German Edition. A version of this article appeared on Medscape.com.

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Lead is significantly more harmful to the health of children and adults across the world than previously thought. This conclusion is suggested by a modeling study presented by Norwegian development economist Bjorn Larsen and the Colombian environmental specialist for lead Ernesto Sánchez-Triana, PhD, in a presentation to the World Bank. Their work was published in The Lancet Planetary Health.

As Mr. Larsen and Mr. Sánchez-Triana report, the economic consequences of increased exposure to lead are already immense, especially in low- and middle-income countries (LMICs). The study was financed by the Korea Green Growth Trust Fund and the World Bank’s Pollution Management and Environmental Health Program.
 

Intellectual, cardiovascular effects

“It is a very important publication that affects all of us,” pediatrician Stephan Böse-O’Reilly, MD, of the Institute and Polyclinic for Occupational, Social, and Environmental Health at Ludwig Maximilian University Hospital in Munich, Germany, said in an interview. “The study, the results of which I think are very reliable, shows that elevated levels of lead in the blood have a much more drastic effect on children’s intelligence than we previously thought.”

It is well known that lead affects the antenatal and postnatal cognitive development of children, Dr. Böse-O’Reilly explained. But the extent of this effect has quite clearly been underestimated before now.

On the other hand, Mr. Larsen and Mr. Sánchez-Triana’s work could prove that lead may lead to more cardiovascular diseases in adulthood. “We already knew that increased exposure to lead increased the risk of high blood pressure and, as a result, mortality,” said Dr. Böse-O’Reilly. “This study now very clearly shows that the risk of arteriosclerosis, for example, also increases through lead exposure.”
 

Figures from 2019

“For the first time, to our knowledge, we aimed to estimate the global burden and cost of IQ loss and cardiovascular disease mortality from lead exposure,” wrote Mr. Larsen and Mr. Sánchez-Triana. For their calculations, the scientists used blood lead level estimates from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019.

They estimated IQ loss in children younger than 5 years using the internationally recognized blood lead level–IQ loss function. The researchers subsequently estimated the cost of this IQ loss based on the loss in lifetime income, presented as cost in U.S. dollars and percentage of gross domestic product (GDP).

Mr. Larsen and Mr. Sánchez-Triana estimated cardiovascular deaths caused by lead exposure in adults aged 25 years or older using a model that captures the effects of lead exposure on cardiovascular disease mortality that is mediated through mechanisms other than hypertension.

Finally, they used the statistical life expectancy to estimate the welfare cost of premature mortality, also presented as cost in U.S. dollars and percentage of GDP. All estimates were calculated according to the World Bank income classification for 2019.
 

Millions of deaths

As reported by Mr. Larsen and Mr. Sánchez-Triana, children younger than 5 years lost an estimated 765 million IQ points worldwide because of lead exposure in this period. In 2019, 5,545,000 adults died from cardiovascular diseases caused by lead exposure. The scientists recorded 729 million of the IQ points lost (95.3%) and 5,004,000 (90.2%) of the deaths as occurring in LMICs.

The IQ loss here was nearly 80% higher than a previous estimate, wrote Mr. Larsen and Mr. Sánchez-Triana. The number of cardiovascular disease deaths they determined was six times higher than the GBD 2019 estimate.



“These are results with which the expert societies, especially the German Society of Pediatrics and Adolescent Medicine and the German Cardiac Society, and the corresponding professional associations need to concern themselves,” said Dr. Böse-O’Reilly.

Although blood lead concentrations have declined substantially since the phase-out of leaded gasoline, especially in Western countries, lead still represents a major health issue because it stays in the bones for decades.

European situation moderate

“We need a broad discussion on questions such as whether lead levels should be included in prophylactic assessments in certain age groups, what blood level is even tolerable, and in what situation medicinal therapy with chelating agents would possibly be appropriate,” said Dr. Böse-O’Reilly.

“Of course, we cannot answer these questions on the basis of one individual study,” he added. “However, the work in question definitely illustrates how dangerous lead can be and that we need further research into the actual burden and the best preventive measures.”

In this respect, the situation in Europe is still comparatively moderate. “Globally, lead exposure has risen in recent years,” said Dr. Böse-O’Reilly. According to an investigation by the Planet Earth Foundation, outside of the European Union, lead can increasingly be found in toys, spices, and cooking utensils, for example.

“Especially in lower-income countries, there is a lack of consumer protection or a good monitoring program like we have here in the EU,” said Dr. Böse-O’Reilly. In these countries, lead is sometimes added to spices by unscrupulous retailers to make the color more intense or to simply add to its weight to gain more profit.

Recycling lead-acid batteries or other electrical waste, often transferred to poorer countries, constitutes a large problem. “In general, children in Germany have a blood lead level of less than 1 mcg/dL,” explained Dr. Böse-O’Reilly. “In some regions of Indonesia, where these recycling factories are located, more than 50% of children have levels of more than 20 mcg/dL.”
 

Particulate matter

According to Mr. Larsen and Mr. Sánchez-Triana, the global cost of increased lead exposure was around $6 trillion USD in 2019, which was equivalent to 6.9% of global GDP. About 77% of the cost ($4.62 trillion USD) comprised the welfare costs of cardiovascular disease mortality, and 23% ($1.38 trillion USD) comprised the present value of future income losses because of IQ loss in children.

“Our findings suggest that global lead exposure has health and economic costs on par with PM2.5 air pollution,” wrote the authors. This places lead as an environmental risk factor on par with particulate matter and above that of air pollution from solid fuels, ahead of unsafe drinking water, unhygienic sanitation, or insufficient handwashing.

“This finding is in contrast to that of GBD 2019, which ranked lead exposure as a distant fourth environmental risk factor, due to not accounting for IQ loss in children – other than idiopathic developmental intellectual disability in a small subset of children – and reporting a substantially lower estimate of adult cardiovascular disease mortality,” wrote Mr. Larsen and Mr. Sánchez-Triana.

“A central implication for future research and policy is that LMICs bear an extraordinarily large share of the health and cost burden of lead exposure,” wrote the authors. Consequently, improved quality of blood lead level measurements and identification of sources containing lead are urgently needed there.
 

Improved recycling methods

Dr. Böse-O’Reilly would like an increased focus on children. “If children’s cognitive skills are lost, this of course has a long-term effect on a country’s economic position,” he said. “Precisely that which LMICs actually need for their development is being stripped from them.

“We should think long and hard about whether we really need to send so much of our electrical waste and so many old cars to poorer countries, where they are incorrectly recycled,” he warned. “We should at least give the LMICs the support necessary for them to be able to process lead-containing products in the future so that less lead makes it into the environment.

“Through these global cycles, we all contribute a lot toward the worldwide lead burden,” Dr. Böse-O’Reilly said. “In my opinion, the German Supply Chain Act is therefore definitely sensible. Not only does it protect our own economy, but it also protects the health of people in other countries.”

This article was translated from Medscape’s German Edition. A version of this article appeared on Medscape.com.

Lead is significantly more harmful to the health of children and adults across the world than previously thought. This conclusion is suggested by a modeling study presented by Norwegian development economist Bjorn Larsen and the Colombian environmental specialist for lead Ernesto Sánchez-Triana, PhD, in a presentation to the World Bank. Their work was published in The Lancet Planetary Health.

As Mr. Larsen and Mr. Sánchez-Triana report, the economic consequences of increased exposure to lead are already immense, especially in low- and middle-income countries (LMICs). The study was financed by the Korea Green Growth Trust Fund and the World Bank’s Pollution Management and Environmental Health Program.
 

Intellectual, cardiovascular effects

“It is a very important publication that affects all of us,” pediatrician Stephan Böse-O’Reilly, MD, of the Institute and Polyclinic for Occupational, Social, and Environmental Health at Ludwig Maximilian University Hospital in Munich, Germany, said in an interview. “The study, the results of which I think are very reliable, shows that elevated levels of lead in the blood have a much more drastic effect on children’s intelligence than we previously thought.”

It is well known that lead affects the antenatal and postnatal cognitive development of children, Dr. Böse-O’Reilly explained. But the extent of this effect has quite clearly been underestimated before now.

On the other hand, Mr. Larsen and Mr. Sánchez-Triana’s work could prove that lead may lead to more cardiovascular diseases in adulthood. “We already knew that increased exposure to lead increased the risk of high blood pressure and, as a result, mortality,” said Dr. Böse-O’Reilly. “This study now very clearly shows that the risk of arteriosclerosis, for example, also increases through lead exposure.”
 

Figures from 2019

“For the first time, to our knowledge, we aimed to estimate the global burden and cost of IQ loss and cardiovascular disease mortality from lead exposure,” wrote Mr. Larsen and Mr. Sánchez-Triana. For their calculations, the scientists used blood lead level estimates from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019.

They estimated IQ loss in children younger than 5 years using the internationally recognized blood lead level–IQ loss function. The researchers subsequently estimated the cost of this IQ loss based on the loss in lifetime income, presented as cost in U.S. dollars and percentage of gross domestic product (GDP).

Mr. Larsen and Mr. Sánchez-Triana estimated cardiovascular deaths caused by lead exposure in adults aged 25 years or older using a model that captures the effects of lead exposure on cardiovascular disease mortality that is mediated through mechanisms other than hypertension.

Finally, they used the statistical life expectancy to estimate the welfare cost of premature mortality, also presented as cost in U.S. dollars and percentage of GDP. All estimates were calculated according to the World Bank income classification for 2019.
 

Millions of deaths

As reported by Mr. Larsen and Mr. Sánchez-Triana, children younger than 5 years lost an estimated 765 million IQ points worldwide because of lead exposure in this period. In 2019, 5,545,000 adults died from cardiovascular diseases caused by lead exposure. The scientists recorded 729 million of the IQ points lost (95.3%) and 5,004,000 (90.2%) of the deaths as occurring in LMICs.

The IQ loss here was nearly 80% higher than a previous estimate, wrote Mr. Larsen and Mr. Sánchez-Triana. The number of cardiovascular disease deaths they determined was six times higher than the GBD 2019 estimate.



“These are results with which the expert societies, especially the German Society of Pediatrics and Adolescent Medicine and the German Cardiac Society, and the corresponding professional associations need to concern themselves,” said Dr. Böse-O’Reilly.

Although blood lead concentrations have declined substantially since the phase-out of leaded gasoline, especially in Western countries, lead still represents a major health issue because it stays in the bones for decades.

European situation moderate

“We need a broad discussion on questions such as whether lead levels should be included in prophylactic assessments in certain age groups, what blood level is even tolerable, and in what situation medicinal therapy with chelating agents would possibly be appropriate,” said Dr. Böse-O’Reilly.

“Of course, we cannot answer these questions on the basis of one individual study,” he added. “However, the work in question definitely illustrates how dangerous lead can be and that we need further research into the actual burden and the best preventive measures.”

In this respect, the situation in Europe is still comparatively moderate. “Globally, lead exposure has risen in recent years,” said Dr. Böse-O’Reilly. According to an investigation by the Planet Earth Foundation, outside of the European Union, lead can increasingly be found in toys, spices, and cooking utensils, for example.

“Especially in lower-income countries, there is a lack of consumer protection or a good monitoring program like we have here in the EU,” said Dr. Böse-O’Reilly. In these countries, lead is sometimes added to spices by unscrupulous retailers to make the color more intense or to simply add to its weight to gain more profit.

Recycling lead-acid batteries or other electrical waste, often transferred to poorer countries, constitutes a large problem. “In general, children in Germany have a blood lead level of less than 1 mcg/dL,” explained Dr. Böse-O’Reilly. “In some regions of Indonesia, where these recycling factories are located, more than 50% of children have levels of more than 20 mcg/dL.”
 

Particulate matter

According to Mr. Larsen and Mr. Sánchez-Triana, the global cost of increased lead exposure was around $6 trillion USD in 2019, which was equivalent to 6.9% of global GDP. About 77% of the cost ($4.62 trillion USD) comprised the welfare costs of cardiovascular disease mortality, and 23% ($1.38 trillion USD) comprised the present value of future income losses because of IQ loss in children.

“Our findings suggest that global lead exposure has health and economic costs on par with PM2.5 air pollution,” wrote the authors. This places lead as an environmental risk factor on par with particulate matter and above that of air pollution from solid fuels, ahead of unsafe drinking water, unhygienic sanitation, or insufficient handwashing.

“This finding is in contrast to that of GBD 2019, which ranked lead exposure as a distant fourth environmental risk factor, due to not accounting for IQ loss in children – other than idiopathic developmental intellectual disability in a small subset of children – and reporting a substantially lower estimate of adult cardiovascular disease mortality,” wrote Mr. Larsen and Mr. Sánchez-Triana.

“A central implication for future research and policy is that LMICs bear an extraordinarily large share of the health and cost burden of lead exposure,” wrote the authors. Consequently, improved quality of blood lead level measurements and identification of sources containing lead are urgently needed there.
 

Improved recycling methods

Dr. Böse-O’Reilly would like an increased focus on children. “If children’s cognitive skills are lost, this of course has a long-term effect on a country’s economic position,” he said. “Precisely that which LMICs actually need for their development is being stripped from them.

“We should think long and hard about whether we really need to send so much of our electrical waste and so many old cars to poorer countries, where they are incorrectly recycled,” he warned. “We should at least give the LMICs the support necessary for them to be able to process lead-containing products in the future so that less lead makes it into the environment.

“Through these global cycles, we all contribute a lot toward the worldwide lead burden,” Dr. Böse-O’Reilly said. “In my opinion, the German Supply Chain Act is therefore definitely sensible. Not only does it protect our own economy, but it also protects the health of people in other countries.”

This article was translated from Medscape’s German Edition. A version of this article appeared on Medscape.com.

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Functional MRI shows that empathetic remarks reduce pain

Article Type
Changed
Thu, 07/20/2023 - 12:57

Physicians’ demonstrations of empathy toward their patients can decrease the sensation of pain. These are the results of a study, recently published in the Proceedings of the National Academy of Sciences, that was conducted by a team led by neuroscientist Dan-Mikael Ellingsen, PhD, from Oslo University Hospital.

The researchers used functional MRI to scan the brains of 20 patients with chronic pain to investigate how a physician’s demeanor may affect patients’ sensitivity to pain, including effects in the central nervous system. During the scans, which were conducted in two sessions, the patients’ legs were exposed to stimuli that ranged from painless to moderately painful. The patients recorded perceived pain intensity using a scale. The physicians also underwent fMRI.

Half of the patients were subjected to the pain stimuli while alone; the other half were subjected to pain while in the presence of a physician. The latter group of patients was divided into two subgroups. Half of the patients had spoken to the accompanying physician before the examination. They discussed the history of the patient’s condition to date, among other things. The other half underwent the brain scans without any prior interaction with a physician.
 

Worse when alone

Dr. Ellingsen and his colleagues found that patients who were alone during the examination reported greater pain than those who were in the presence of a physician, even though they were subjected to stimuli of the same intensity. In instances in which the physician and patient had already spoken before the brain scan, patients additionally felt that the physician was empathetic and understood their pain. Furthermore, the physicians were better able to estimate the pain that their patients experienced.

The patients who had a physician by their side consistently experienced pain that was milder than the pain experienced by those who were alone. For pairs that had spoken beforehand, the patients considered their physician to be better able to understand their pain, and the physicians estimated the perceived pain intensity of their patients more accurately.
 

Evidence of trust

There was greater activity in the dorsolateral and ventrolateral prefrontal cortex, as well as in the primary and secondary somatosensory areas, in patients in the subgroup that had spoken to a physician. For the physicians, compared with the comparison group, there was an increase in correspondence between activity in the dorsolateral prefrontal cortex and activity in the secondary somatosensory areas of patients, which is a brain region that is known to react to pain. The brain activity correlation increased in line with the self-reported mutual trust between the physician and patient.

“These results prove that empathy and support can decrease pain intensity,” the investigators write. The data shed light on the brain processes behind the social modulation of pain during the interaction between the physician and the patient. Concordances in the brain are increased by greater therapeutic alliance.
 

Beyond medication

Winfried Meissner, MD, head of the pain clinic at the department of anesthesiology and intensive care medicine at Jena University Hospital, Germany, and former president of the German Pain Society, said in an interview: “I view this as a vital study that impressively demonstrates that effective, intensive pain therapy is not just a case of administering the correct analgesic.”

“Instead, a focus should be placed on what common sense tells us, which is just how crucial an empathetic attitude from physicians and good communication with patients are when it comes to the success of any therapy,” Dr. Meissner added. Unfortunately, such an attitude and such communication often are not provided in clinical practice because of limitations on time.

“Now, with objectively collected data from patients and physicians, [Dr.] Ellingsen’s team has been able to demonstrate that human interaction has a decisive impact on the treatment of patients experiencing pain,” said Dr. Meissner. “The study should encourage practitioners to treat communication just as seriously as the pharmacology of analgesics.”
 

Perception and attitude

“The study shows remarkably well that empathetic conversation between the physician and patient represents a valuable therapeutic method and should be recognized as such,” emphasized Dr. Meissner. Of course, conversation cannot replace pharmacologic treatment, but it can supplement and reinforce it. Furthermore, a physician’s empathy presumably has an effect that is at least as great as a suitable analgesic.

“Pain is more than just sensory perception,” explained Dr. Meissner. “We all know that it has a strong affective component, and perception is greatly determined by context.” This can be seen, for example, in athletes, who often attribute less importance to their pain and can successfully perform competitively despite a painful injury.
 

Positive expectations

Dr. Meissner advised all physicians to treat patients with pain empathetically. He encourages them to ask patients about their pain, accompanying symptoms, possible fears, and other mental stress and to take these factors seriously.

Moreover, the findings accentuate the effect of prescribed analgesics. “Numerous studies have meanwhile shown that the more positive a patient’s expectations, the better the effect of a medication,” said Dr. Meissner. “We physicians must exploit this effect, too.”

This article was translated from the Medscape German Edition and a version appeared on Medscape.com.

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Physicians’ demonstrations of empathy toward their patients can decrease the sensation of pain. These are the results of a study, recently published in the Proceedings of the National Academy of Sciences, that was conducted by a team led by neuroscientist Dan-Mikael Ellingsen, PhD, from Oslo University Hospital.

The researchers used functional MRI to scan the brains of 20 patients with chronic pain to investigate how a physician’s demeanor may affect patients’ sensitivity to pain, including effects in the central nervous system. During the scans, which were conducted in two sessions, the patients’ legs were exposed to stimuli that ranged from painless to moderately painful. The patients recorded perceived pain intensity using a scale. The physicians also underwent fMRI.

Half of the patients were subjected to the pain stimuli while alone; the other half were subjected to pain while in the presence of a physician. The latter group of patients was divided into two subgroups. Half of the patients had spoken to the accompanying physician before the examination. They discussed the history of the patient’s condition to date, among other things. The other half underwent the brain scans without any prior interaction with a physician.
 

Worse when alone

Dr. Ellingsen and his colleagues found that patients who were alone during the examination reported greater pain than those who were in the presence of a physician, even though they were subjected to stimuli of the same intensity. In instances in which the physician and patient had already spoken before the brain scan, patients additionally felt that the physician was empathetic and understood their pain. Furthermore, the physicians were better able to estimate the pain that their patients experienced.

The patients who had a physician by their side consistently experienced pain that was milder than the pain experienced by those who were alone. For pairs that had spoken beforehand, the patients considered their physician to be better able to understand their pain, and the physicians estimated the perceived pain intensity of their patients more accurately.
 

Evidence of trust

There was greater activity in the dorsolateral and ventrolateral prefrontal cortex, as well as in the primary and secondary somatosensory areas, in patients in the subgroup that had spoken to a physician. For the physicians, compared with the comparison group, there was an increase in correspondence between activity in the dorsolateral prefrontal cortex and activity in the secondary somatosensory areas of patients, which is a brain region that is known to react to pain. The brain activity correlation increased in line with the self-reported mutual trust between the physician and patient.

“These results prove that empathy and support can decrease pain intensity,” the investigators write. The data shed light on the brain processes behind the social modulation of pain during the interaction between the physician and the patient. Concordances in the brain are increased by greater therapeutic alliance.
 

Beyond medication

Winfried Meissner, MD, head of the pain clinic at the department of anesthesiology and intensive care medicine at Jena University Hospital, Germany, and former president of the German Pain Society, said in an interview: “I view this as a vital study that impressively demonstrates that effective, intensive pain therapy is not just a case of administering the correct analgesic.”

“Instead, a focus should be placed on what common sense tells us, which is just how crucial an empathetic attitude from physicians and good communication with patients are when it comes to the success of any therapy,” Dr. Meissner added. Unfortunately, such an attitude and such communication often are not provided in clinical practice because of limitations on time.

“Now, with objectively collected data from patients and physicians, [Dr.] Ellingsen’s team has been able to demonstrate that human interaction has a decisive impact on the treatment of patients experiencing pain,” said Dr. Meissner. “The study should encourage practitioners to treat communication just as seriously as the pharmacology of analgesics.”
 

Perception and attitude

“The study shows remarkably well that empathetic conversation between the physician and patient represents a valuable therapeutic method and should be recognized as such,” emphasized Dr. Meissner. Of course, conversation cannot replace pharmacologic treatment, but it can supplement and reinforce it. Furthermore, a physician’s empathy presumably has an effect that is at least as great as a suitable analgesic.

“Pain is more than just sensory perception,” explained Dr. Meissner. “We all know that it has a strong affective component, and perception is greatly determined by context.” This can be seen, for example, in athletes, who often attribute less importance to their pain and can successfully perform competitively despite a painful injury.
 

Positive expectations

Dr. Meissner advised all physicians to treat patients with pain empathetically. He encourages them to ask patients about their pain, accompanying symptoms, possible fears, and other mental stress and to take these factors seriously.

Moreover, the findings accentuate the effect of prescribed analgesics. “Numerous studies have meanwhile shown that the more positive a patient’s expectations, the better the effect of a medication,” said Dr. Meissner. “We physicians must exploit this effect, too.”

This article was translated from the Medscape German Edition and a version appeared on Medscape.com.

Physicians’ demonstrations of empathy toward their patients can decrease the sensation of pain. These are the results of a study, recently published in the Proceedings of the National Academy of Sciences, that was conducted by a team led by neuroscientist Dan-Mikael Ellingsen, PhD, from Oslo University Hospital.

The researchers used functional MRI to scan the brains of 20 patients with chronic pain to investigate how a physician’s demeanor may affect patients’ sensitivity to pain, including effects in the central nervous system. During the scans, which were conducted in two sessions, the patients’ legs were exposed to stimuli that ranged from painless to moderately painful. The patients recorded perceived pain intensity using a scale. The physicians also underwent fMRI.

Half of the patients were subjected to the pain stimuli while alone; the other half were subjected to pain while in the presence of a physician. The latter group of patients was divided into two subgroups. Half of the patients had spoken to the accompanying physician before the examination. They discussed the history of the patient’s condition to date, among other things. The other half underwent the brain scans without any prior interaction with a physician.
 

Worse when alone

Dr. Ellingsen and his colleagues found that patients who were alone during the examination reported greater pain than those who were in the presence of a physician, even though they were subjected to stimuli of the same intensity. In instances in which the physician and patient had already spoken before the brain scan, patients additionally felt that the physician was empathetic and understood their pain. Furthermore, the physicians were better able to estimate the pain that their patients experienced.

The patients who had a physician by their side consistently experienced pain that was milder than the pain experienced by those who were alone. For pairs that had spoken beforehand, the patients considered their physician to be better able to understand their pain, and the physicians estimated the perceived pain intensity of their patients more accurately.
 

Evidence of trust

There was greater activity in the dorsolateral and ventrolateral prefrontal cortex, as well as in the primary and secondary somatosensory areas, in patients in the subgroup that had spoken to a physician. For the physicians, compared with the comparison group, there was an increase in correspondence between activity in the dorsolateral prefrontal cortex and activity in the secondary somatosensory areas of patients, which is a brain region that is known to react to pain. The brain activity correlation increased in line with the self-reported mutual trust between the physician and patient.

“These results prove that empathy and support can decrease pain intensity,” the investigators write. The data shed light on the brain processes behind the social modulation of pain during the interaction between the physician and the patient. Concordances in the brain are increased by greater therapeutic alliance.
 

Beyond medication

Winfried Meissner, MD, head of the pain clinic at the department of anesthesiology and intensive care medicine at Jena University Hospital, Germany, and former president of the German Pain Society, said in an interview: “I view this as a vital study that impressively demonstrates that effective, intensive pain therapy is not just a case of administering the correct analgesic.”

“Instead, a focus should be placed on what common sense tells us, which is just how crucial an empathetic attitude from physicians and good communication with patients are when it comes to the success of any therapy,” Dr. Meissner added. Unfortunately, such an attitude and such communication often are not provided in clinical practice because of limitations on time.

“Now, with objectively collected data from patients and physicians, [Dr.] Ellingsen’s team has been able to demonstrate that human interaction has a decisive impact on the treatment of patients experiencing pain,” said Dr. Meissner. “The study should encourage practitioners to treat communication just as seriously as the pharmacology of analgesics.”
 

Perception and attitude

“The study shows remarkably well that empathetic conversation between the physician and patient represents a valuable therapeutic method and should be recognized as such,” emphasized Dr. Meissner. Of course, conversation cannot replace pharmacologic treatment, but it can supplement and reinforce it. Furthermore, a physician’s empathy presumably has an effect that is at least as great as a suitable analgesic.

“Pain is more than just sensory perception,” explained Dr. Meissner. “We all know that it has a strong affective component, and perception is greatly determined by context.” This can be seen, for example, in athletes, who often attribute less importance to their pain and can successfully perform competitively despite a painful injury.
 

Positive expectations

Dr. Meissner advised all physicians to treat patients with pain empathetically. He encourages them to ask patients about their pain, accompanying symptoms, possible fears, and other mental stress and to take these factors seriously.

Moreover, the findings accentuate the effect of prescribed analgesics. “Numerous studies have meanwhile shown that the more positive a patient’s expectations, the better the effect of a medication,” said Dr. Meissner. “We physicians must exploit this effect, too.”

This article was translated from the Medscape German Edition and a version appeared on Medscape.com.

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Induced labor associated with poor school performance of offspring

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Fri, 03/10/2023 - 13:38

On average, children born following induced labor perform worse at school at age 12 years than their peers who were born after spontaneous onset of labor. This is the outcome of a report by Anita Ravelli, PhD, and her team of Dutch researchers in the department of obstetrics and gynecology of the Amsterdam University Medical Center, published in Acta Obstetricia et Gynecologica Scandinavica.

For the retrospective cohort study, the team analyzed data from almost 230,000 patients. According to these data, the likelihood of children reaching higher secondary school level is around 10% lower after elective induction of labor.
 

Labor induction frequent

These days in Germany, more than 20% of all births are induced. Sometimes this decision is made because of medical reasons, such as the woman’s having gestational diabetes, the presence of gestational toxicity, or the occurrence of a premature rupture of membranes. However, contractions are most often artificially triggered because the expected delivery date has passed.

Guidelines from the German Society of Gynecology and Obstetrics recommend inducing labor if there is a medical indication and if more than 10 days have passed since the expected delivery date. After 14 days, induction is strongly advised. This recommendation is based on studies that indicate that the child is at increased risk of disease and death once the expected delivery date is far exceeded.
 

Causal relationship unproven

It is still unclear whether and to what extent inducing labor affects a child’s neurologic development. Since the frequency of induced labor has increased greatly worldwide, Dr. Ravelli and her colleagues investigated this matter.

The study may have limited validity, however. “The outcome of the study only determines an association between spontaneous labor in mature children versus induced labor and a school performance test at 12 years of age,” said Maria Delius, MD, MPH, head of the Perinatal Center at the Clinic and Polyclinic for Obstetrics and Gynecology of the Ludwig Maximilian University of Munich. “The study is unable to prove any causality, even if it sounds that way in the abstract.”

This publication may in no way instigate a change in current practices, Dr. Delius emphasized. “There is a lot of potential for the wrong conclusions to be drawn from this study, and as a result – if it is presented and perceived in a subjective manner in public – to also cause harm to mothers and children,” she warned. The study also must not be associated with the drug misoprostol, since the various mechanical and medicinal methods of induction were not the topic of the Dutch investigation.
 

Gestational-week differences

The primary author of the study, Renee J. Burger, MD, PhD, of Dr. Ravelli’s UMC team, and her colleagues assessed the school performance of 226,684 children at age 12 years who were born in the 37th to 42nd week of gestation (WOG) between 2003 and 2008 in the Netherlands following an uncomplicated single pregnancy. They compared school performance, divided for each of the six WOG analyzed, between children whose birth was mechanically or medicinally induced and those who were born without intervention.

 

 

According to the report by the researchers, induced labor at every WOG up to the 41st week was associated with lower school performance in the children, compared with a spontaneous birth. In addition, fewer children whose birth was induced reached a higher secondary level of education. After 38 WOG, the figure stood at 48%, compared with 54% of children who were born without intervention. For 12-year-olds not born until the 42nd WOG, there were no significant differences between the two groups investigated.
 

Prospective studies pending

Dr. Burger and Dr. Ravelli emphasized that the results do not indicate that every child born after an induced labor will perform worse at school. This is a statistical correlation that cannot be transferred to a case-by-case basis. In addition, it is unlikely that all disruptive factors could be taken into consideration during the analyses. Nonetheless, the researchers conclude that the long-term effects of inducing labor should be considered during consultation and decision-making in the future.

In general, it is important that future randomized, controlled studies incorporate long-term measurements in their results and conclusions so that complete data on the present topic can be gathered. “Although the effect on the individual child is likely subtle, the impact on society due to the large number of early-term labor inductions should not be underestimated,” the authors wrote.
 

Unexamined disruptive factors

Sven Kehl, MD, PhD, senior physician of the department of obstetrics and gynecology and coordinator of the University Perinatal Center of Franconia at the University Hospital of Erlangen, Germany, is of a similar opinion. “Inducing labor causes birth to occur sooner and therefore for the pregnancy to finish prematurely,” said Dr. Kehl. Such premature births, not the mechanical or medicinal procedures for inducing labor, could affect the child’s cerebral development. “The results of this study suggest that inducing labor in uncomplicated pregnancies, in which there are no relevant medical indications, should be avoided,” said Dr. Kehl. In these cases, the mother should wait for a natural birth.

Some of the study’s strengths include the large quantity of data, the large number of participants, and the various disruptive factors taken into consideration, such as the mother’s level of education, according to Dr. Kehl. “But it is not a study from which causality can be derived,” he said.

Not all the potential disruptive factors could be found in the available data. For example, information regarding familial status, the father’s level of education, the parents’ smoking status, or the mother’s body mass index was missing. Also, only a small number of the possible indications for inducing labor was disclosed.
 

No elective inductions

The study is unlikely to have a major effect on practice in German maternity clinics, since the routine induction of labor from the 39th WOG has always been regarded critically in German-speaking countries, said Dr. Kehl. It is still true that if there are any risks, a risk-benefit analysis must be performed, and the risks to the mother or child must be evaluated when considering labor induction.

“If there are no medical reasons for inducing labor, the women must also be informed about the possible long-term consequences and not just about the short-term risks,” said Dr. Kehl.

His colleague in Berlin, Michael Abou-Dakn, MD, chief physician of gynecology and obstetrics at the St. Joseph’s Hospital, Berlin-Tempelhof, was more categorical. “It is right to criticize the fact that over 20% of births in Germany are induced,” he said. He is rather dubious, however, about the effects on school performance found in the study following induced labor. Still, the investigation is a reminder that inducing labor could involve side effects. “There should therefore be no elective inductions, or any without a clear indication,” said Dr. Abou-Dakn.

This article was translated from the Medscape German Edition and a version appeared on Medscape.com.

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On average, children born following induced labor perform worse at school at age 12 years than their peers who were born after spontaneous onset of labor. This is the outcome of a report by Anita Ravelli, PhD, and her team of Dutch researchers in the department of obstetrics and gynecology of the Amsterdam University Medical Center, published in Acta Obstetricia et Gynecologica Scandinavica.

For the retrospective cohort study, the team analyzed data from almost 230,000 patients. According to these data, the likelihood of children reaching higher secondary school level is around 10% lower after elective induction of labor.
 

Labor induction frequent

These days in Germany, more than 20% of all births are induced. Sometimes this decision is made because of medical reasons, such as the woman’s having gestational diabetes, the presence of gestational toxicity, or the occurrence of a premature rupture of membranes. However, contractions are most often artificially triggered because the expected delivery date has passed.

Guidelines from the German Society of Gynecology and Obstetrics recommend inducing labor if there is a medical indication and if more than 10 days have passed since the expected delivery date. After 14 days, induction is strongly advised. This recommendation is based on studies that indicate that the child is at increased risk of disease and death once the expected delivery date is far exceeded.
 

Causal relationship unproven

It is still unclear whether and to what extent inducing labor affects a child’s neurologic development. Since the frequency of induced labor has increased greatly worldwide, Dr. Ravelli and her colleagues investigated this matter.

The study may have limited validity, however. “The outcome of the study only determines an association between spontaneous labor in mature children versus induced labor and a school performance test at 12 years of age,” said Maria Delius, MD, MPH, head of the Perinatal Center at the Clinic and Polyclinic for Obstetrics and Gynecology of the Ludwig Maximilian University of Munich. “The study is unable to prove any causality, even if it sounds that way in the abstract.”

This publication may in no way instigate a change in current practices, Dr. Delius emphasized. “There is a lot of potential for the wrong conclusions to be drawn from this study, and as a result – if it is presented and perceived in a subjective manner in public – to also cause harm to mothers and children,” she warned. The study also must not be associated with the drug misoprostol, since the various mechanical and medicinal methods of induction were not the topic of the Dutch investigation.
 

Gestational-week differences

The primary author of the study, Renee J. Burger, MD, PhD, of Dr. Ravelli’s UMC team, and her colleagues assessed the school performance of 226,684 children at age 12 years who were born in the 37th to 42nd week of gestation (WOG) between 2003 and 2008 in the Netherlands following an uncomplicated single pregnancy. They compared school performance, divided for each of the six WOG analyzed, between children whose birth was mechanically or medicinally induced and those who were born without intervention.

 

 

According to the report by the researchers, induced labor at every WOG up to the 41st week was associated with lower school performance in the children, compared with a spontaneous birth. In addition, fewer children whose birth was induced reached a higher secondary level of education. After 38 WOG, the figure stood at 48%, compared with 54% of children who were born without intervention. For 12-year-olds not born until the 42nd WOG, there were no significant differences between the two groups investigated.
 

Prospective studies pending

Dr. Burger and Dr. Ravelli emphasized that the results do not indicate that every child born after an induced labor will perform worse at school. This is a statistical correlation that cannot be transferred to a case-by-case basis. In addition, it is unlikely that all disruptive factors could be taken into consideration during the analyses. Nonetheless, the researchers conclude that the long-term effects of inducing labor should be considered during consultation and decision-making in the future.

In general, it is important that future randomized, controlled studies incorporate long-term measurements in their results and conclusions so that complete data on the present topic can be gathered. “Although the effect on the individual child is likely subtle, the impact on society due to the large number of early-term labor inductions should not be underestimated,” the authors wrote.
 

Unexamined disruptive factors

Sven Kehl, MD, PhD, senior physician of the department of obstetrics and gynecology and coordinator of the University Perinatal Center of Franconia at the University Hospital of Erlangen, Germany, is of a similar opinion. “Inducing labor causes birth to occur sooner and therefore for the pregnancy to finish prematurely,” said Dr. Kehl. Such premature births, not the mechanical or medicinal procedures for inducing labor, could affect the child’s cerebral development. “The results of this study suggest that inducing labor in uncomplicated pregnancies, in which there are no relevant medical indications, should be avoided,” said Dr. Kehl. In these cases, the mother should wait for a natural birth.

Some of the study’s strengths include the large quantity of data, the large number of participants, and the various disruptive factors taken into consideration, such as the mother’s level of education, according to Dr. Kehl. “But it is not a study from which causality can be derived,” he said.

Not all the potential disruptive factors could be found in the available data. For example, information regarding familial status, the father’s level of education, the parents’ smoking status, or the mother’s body mass index was missing. Also, only a small number of the possible indications for inducing labor was disclosed.
 

No elective inductions

The study is unlikely to have a major effect on practice in German maternity clinics, since the routine induction of labor from the 39th WOG has always been regarded critically in German-speaking countries, said Dr. Kehl. It is still true that if there are any risks, a risk-benefit analysis must be performed, and the risks to the mother or child must be evaluated when considering labor induction.

“If there are no medical reasons for inducing labor, the women must also be informed about the possible long-term consequences and not just about the short-term risks,” said Dr. Kehl.

His colleague in Berlin, Michael Abou-Dakn, MD, chief physician of gynecology and obstetrics at the St. Joseph’s Hospital, Berlin-Tempelhof, was more categorical. “It is right to criticize the fact that over 20% of births in Germany are induced,” he said. He is rather dubious, however, about the effects on school performance found in the study following induced labor. Still, the investigation is a reminder that inducing labor could involve side effects. “There should therefore be no elective inductions, or any without a clear indication,” said Dr. Abou-Dakn.

This article was translated from the Medscape German Edition and a version appeared on Medscape.com.

On average, children born following induced labor perform worse at school at age 12 years than their peers who were born after spontaneous onset of labor. This is the outcome of a report by Anita Ravelli, PhD, and her team of Dutch researchers in the department of obstetrics and gynecology of the Amsterdam University Medical Center, published in Acta Obstetricia et Gynecologica Scandinavica.

For the retrospective cohort study, the team analyzed data from almost 230,000 patients. According to these data, the likelihood of children reaching higher secondary school level is around 10% lower after elective induction of labor.
 

Labor induction frequent

These days in Germany, more than 20% of all births are induced. Sometimes this decision is made because of medical reasons, such as the woman’s having gestational diabetes, the presence of gestational toxicity, or the occurrence of a premature rupture of membranes. However, contractions are most often artificially triggered because the expected delivery date has passed.

Guidelines from the German Society of Gynecology and Obstetrics recommend inducing labor if there is a medical indication and if more than 10 days have passed since the expected delivery date. After 14 days, induction is strongly advised. This recommendation is based on studies that indicate that the child is at increased risk of disease and death once the expected delivery date is far exceeded.
 

Causal relationship unproven

It is still unclear whether and to what extent inducing labor affects a child’s neurologic development. Since the frequency of induced labor has increased greatly worldwide, Dr. Ravelli and her colleagues investigated this matter.

The study may have limited validity, however. “The outcome of the study only determines an association between spontaneous labor in mature children versus induced labor and a school performance test at 12 years of age,” said Maria Delius, MD, MPH, head of the Perinatal Center at the Clinic and Polyclinic for Obstetrics and Gynecology of the Ludwig Maximilian University of Munich. “The study is unable to prove any causality, even if it sounds that way in the abstract.”

This publication may in no way instigate a change in current practices, Dr. Delius emphasized. “There is a lot of potential for the wrong conclusions to be drawn from this study, and as a result – if it is presented and perceived in a subjective manner in public – to also cause harm to mothers and children,” she warned. The study also must not be associated with the drug misoprostol, since the various mechanical and medicinal methods of induction were not the topic of the Dutch investigation.
 

Gestational-week differences

The primary author of the study, Renee J. Burger, MD, PhD, of Dr. Ravelli’s UMC team, and her colleagues assessed the school performance of 226,684 children at age 12 years who were born in the 37th to 42nd week of gestation (WOG) between 2003 and 2008 in the Netherlands following an uncomplicated single pregnancy. They compared school performance, divided for each of the six WOG analyzed, between children whose birth was mechanically or medicinally induced and those who were born without intervention.

 

 

According to the report by the researchers, induced labor at every WOG up to the 41st week was associated with lower school performance in the children, compared with a spontaneous birth. In addition, fewer children whose birth was induced reached a higher secondary level of education. After 38 WOG, the figure stood at 48%, compared with 54% of children who were born without intervention. For 12-year-olds not born until the 42nd WOG, there were no significant differences between the two groups investigated.
 

Prospective studies pending

Dr. Burger and Dr. Ravelli emphasized that the results do not indicate that every child born after an induced labor will perform worse at school. This is a statistical correlation that cannot be transferred to a case-by-case basis. In addition, it is unlikely that all disruptive factors could be taken into consideration during the analyses. Nonetheless, the researchers conclude that the long-term effects of inducing labor should be considered during consultation and decision-making in the future.

In general, it is important that future randomized, controlled studies incorporate long-term measurements in their results and conclusions so that complete data on the present topic can be gathered. “Although the effect on the individual child is likely subtle, the impact on society due to the large number of early-term labor inductions should not be underestimated,” the authors wrote.
 

Unexamined disruptive factors

Sven Kehl, MD, PhD, senior physician of the department of obstetrics and gynecology and coordinator of the University Perinatal Center of Franconia at the University Hospital of Erlangen, Germany, is of a similar opinion. “Inducing labor causes birth to occur sooner and therefore for the pregnancy to finish prematurely,” said Dr. Kehl. Such premature births, not the mechanical or medicinal procedures for inducing labor, could affect the child’s cerebral development. “The results of this study suggest that inducing labor in uncomplicated pregnancies, in which there are no relevant medical indications, should be avoided,” said Dr. Kehl. In these cases, the mother should wait for a natural birth.

Some of the study’s strengths include the large quantity of data, the large number of participants, and the various disruptive factors taken into consideration, such as the mother’s level of education, according to Dr. Kehl. “But it is not a study from which causality can be derived,” he said.

Not all the potential disruptive factors could be found in the available data. For example, information regarding familial status, the father’s level of education, the parents’ smoking status, or the mother’s body mass index was missing. Also, only a small number of the possible indications for inducing labor was disclosed.
 

No elective inductions

The study is unlikely to have a major effect on practice in German maternity clinics, since the routine induction of labor from the 39th WOG has always been regarded critically in German-speaking countries, said Dr. Kehl. It is still true that if there are any risks, a risk-benefit analysis must be performed, and the risks to the mother or child must be evaluated when considering labor induction.

“If there are no medical reasons for inducing labor, the women must also be informed about the possible long-term consequences and not just about the short-term risks,” said Dr. Kehl.

His colleague in Berlin, Michael Abou-Dakn, MD, chief physician of gynecology and obstetrics at the St. Joseph’s Hospital, Berlin-Tempelhof, was more categorical. “It is right to criticize the fact that over 20% of births in Germany are induced,” he said. He is rather dubious, however, about the effects on school performance found in the study following induced labor. Still, the investigation is a reminder that inducing labor could involve side effects. “There should therefore be no elective inductions, or any without a clear indication,” said Dr. Abou-Dakn.

This article was translated from the Medscape German Edition and a version appeared on Medscape.com.

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