Opioid Resource Center

Four years ago, Atrium Health, in Charlotte, N.C., embarked on a dramatic change in how it cares for newborns exposed to opioids in the womb.

Until then, most of the 700 or so babies who underwent opioid withdrawal each year in the hospital system spent their first weeks in a neonatal intensive care unit (NICU), isolated from their parents and treated with regular doses of morphine to ease their symptoms.

Now, most babies stay in the hospital for just a few days under a new approach called Eat, Sleep, Console. These young patients stay in private rooms where they can bond with their parents and volunteer caregivers. The usual course of treatment is no longer extended therapy with opioid replacements. Instead, mothers are encouraged to stay overnight and are taught how to sooth their babies with swaddling, rocking, and cooing.

As a result, the average length of stay for newborns with neonatal abstinence syndrome (NAS) has dropped from 12 days to 6. Use of morphine has fallen by 79%, from 2.25 to 0.45 mg/kg per stay, according to results of a quality improvement pilot project at one of Atrium’s community hospitals.

Similar outcomes from other hospitals around the country have led to widespread uptake of Eat, Sleep, Console since its advent in 2017. That year, according to federal data, seven newborns were diagnosed with NAS for every 1,000 births.

Advocates say the family-centric model helps parents feel less stigmatized and more confident in their ability to care for their babies, who can have symptoms such as irritability and difficulty feeding for months.

The approach “really empowers families to do what they do best, which is take care of each other,” Douglas Dodds, MD, a pediatrician who led the effort at Atrium, told this news organization.
 

Questioning the old protocols

Numerous state perinatal collaboratives, hospital associations, and health systems say the program is the new standard of care for infants with NAS and neonatal opioid withdrawal syndrome (NOWS).

Twenty-six hospitals have adopted Eat, Sleep, Console as part of a clinical trial sponsored by the National Institutes of Health and a program called Advancing Clinical Trials in Neonatal Opioid Withdrawal Syndrome (ACT NOW). Researchers are comparing the approach to previous care protocols in regard to 12 outcomes, including time to medical readiness for discharge, frequency of opioid replacement therapy, and safety problems, such as seizures during treatment.

The transition has been swift. Less than a decade ago, most hospitals used the Finnegan Neonatal Abstinence Scoring System, which was developed in the 1970s to assess babies whose mothers had used heroin during pregnancy.

The Finnegan score entails monitoring babies every 3 hours for 21 symptoms, including high-pitched crying, sneezing, gastrointestinal problems, and yawning. If a baby scores an 8 or more three times in a row, most protocols using the traditional Finnegan approach recommend that providers move infants to an NICU, where they receive morphine or methadone. Once opioid replacement therapy is started, the protocols require a gradual weaning that lasts 3-4 weeks.

As the opioid epidemic grew and NICUs around the country began to fill with babies experiencing NAS or NOW, some clinicians began to question the Finnegan-driven approach.

“You have these miserable babies who are going through this really tough experience, and our first move is to separate them from their moms,” said Matthew Grossman, MD, a pediatric hospitalist at Yale New Haven Children’s Hospital, New Haven, Conn., who created Eat, Sleep, Console.

Dr. Grossman, associate professor and vice chair for quality in the department of pediatrics at Yale University, said he noticed that when mothers stayed overnight with their babies, the infants tended to have fewer withdrawal symptoms. Indeed, previous studies had demonstrated the benefits of breastfeeding and allowing mothers and babies to share a room.

“If you think of mom as a medicine, then you can’t put the baby in a unit where the mom can’t be there,” Dr. Grossman told this news organization. “It would be like taking a kid with pneumonia and putting him in a unit that doesn’t have antibiotics.”

Despite its prominence, the Finnegan score has never been validated for guiding the treatment of NAS. In addition, Finnegan scores can be inconsistent, and the assessment requires disturbing an infant to check signs such as its startle reflex, which, as Dr. Grossman and his fellow researchers pointed out, flies in the face of American Academy of Pediatrics’ recommendations to prioritize swaddling and minimize stimulation for infants with NAS.

By contrast, Eat, Sleep, Console offers a simplified assessment. Interventions are called for if a baby eats less than an ounce of food at a time/does not breastfeed, sleeps less than an hour at a stretch, or takes more than 10 minutes to be consoled. After nonpharmacologic interventions have been tried, doses of medication are used as needed. Babies who are doing well can be discharged in as few as 4 days.
 

Quashing bias against parents with substance abuse disorder

Even with the promise of shorter stays and better care, switching to nonpharmacologic care presents hurdles for hospitals. Among these is a lack of physical space for mothers to room with their babies in a quiet environment.

“In many community hospitals, the only place for infants to go is a neonatal intensive care unit, outside of the newborn nursery,” said Stephen Patrick, MD, MPH, associate professor and director of the Center for Child Health Policy at Vanderbilt University, Nashville, Tenn., who researches stigma associated with opioid use during pregnancy.

Administrators at SSM St. Mary’s Hospital in St. Louis initially balked at providing private rooms for mothers and their babies with NAS and NOWS, according to Kimberly Spence, MD, a neonatologist at SSM Health. She said the initial plan was to put the babies in a busy, brightly lit nursery.

But resistance waned as the hospital convinced health plans to pay for private rooms for the 5-7 days it typically takes a baby to go through withdrawal, said Dr. Spence, associate professor of pediatrics at Saint Louis University.

“We were able to provide enough data that this is evidence-based medicine and babies do better with their moms, and that ethically, this is the right thing to do, to reduce transfers to an NICU,” she said.

In addition, news stories about the family-centric approach and shorter stays for infants, along with SSM’s launch of an outpatient clinic to treat pregnant women with opioid use disorder, helped the system to attract more patients and increase its market share, said Dr. Spence.

Another challenge was getting physicians and nurses to set aside any judgments of parents with substance abuse disorder, according to Dr. Grossman and others.

“A lot of faculty and staff on the medical team didn’t feel like we should trust moms with their babies’ medical care” at SSM, Dr. Spence said.

Some hospitals conduct anti-bias training to teach providers that substance abuse is a disease that deserves proper medical treatment and not the moral failing of a patient. Such education may involve explaining that babies’ outcomes are improved when women undergo treatment with methadone or buprenorphine during pregnancy, even though use of those medications does pose a risk of NAS.

Creating a system that supports parents with substance abuse disorders may help to change perceptions. At Atrium Health, some staff members now enjoy working with these families because they can make a profound impact, Dr. Dodds said. He said they’ve learned that families suffering from substance abuse disorder “are not that different than any other family.”

Dr. Dodds, Dr. Patrick, Dr. Spence, and Dr. Grossman reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Four years ago, Atrium Health, in Charlotte, N.C., embarked on a dramatic change in how it cares for newborns exposed to opioids in the womb.

Until then, most of the 700 or so babies who underwent opioid withdrawal each year in the hospital system spent their first weeks in a neonatal intensive care unit (NICU), isolated from their parents and treated with regular doses of morphine to ease their symptoms.

Now, most babies stay in the hospital for just a few days under a new approach called Eat, Sleep, Console. These young patients stay in private rooms where they can bond with their parents and volunteer caregivers. The usual course of treatment is no longer extended therapy with opioid replacements. Instead, mothers are encouraged to stay overnight and are taught how to sooth their babies with swaddling, rocking, and cooing.

As a result, the average length of stay for newborns with neonatal abstinence syndrome (NAS) has dropped from 12 days to 6. Use of morphine has fallen by 79%, from 2.25 to 0.45 mg/kg per stay, according to results of a quality improvement pilot project at one of Atrium’s community hospitals.

Similar outcomes from other hospitals around the country have led to widespread uptake of Eat, Sleep, Console since its advent in 2017. That year, according to federal data, seven newborns were diagnosed with NAS for every 1,000 births.

Advocates say the family-centric model helps parents feel less stigmatized and more confident in their ability to care for their babies, who can have symptoms such as irritability and difficulty feeding for months.

The approach “really empowers families to do what they do best, which is take care of each other,” Douglas Dodds, MD, a pediatrician who led the effort at Atrium, told this news organization.
 

Questioning the old protocols

Numerous state perinatal collaboratives, hospital associations, and health systems say the program is the new standard of care for infants with NAS and neonatal opioid withdrawal syndrome (NOWS).

Twenty-six hospitals have adopted Eat, Sleep, Console as part of a clinical trial sponsored by the National Institutes of Health and a program called Advancing Clinical Trials in Neonatal Opioid Withdrawal Syndrome (ACT NOW). Researchers are comparing the approach to previous care protocols in regard to 12 outcomes, including time to medical readiness for discharge, frequency of opioid replacement therapy, and safety problems, such as seizures during treatment.

The transition has been swift. Less than a decade ago, most hospitals used the Finnegan Neonatal Abstinence Scoring System, which was developed in the 1970s to assess babies whose mothers had used heroin during pregnancy.

The Finnegan score entails monitoring babies every 3 hours for 21 symptoms, including high-pitched crying, sneezing, gastrointestinal problems, and yawning. If a baby scores an 8 or more three times in a row, most protocols using the traditional Finnegan approach recommend that providers move infants to an NICU, where they receive morphine or methadone. Once opioid replacement therapy is started, the protocols require a gradual weaning that lasts 3-4 weeks.

As the opioid epidemic grew and NICUs around the country began to fill with babies experiencing NAS or NOW, some clinicians began to question the Finnegan-driven approach.

“You have these miserable babies who are going through this really tough experience, and our first move is to separate them from their moms,” said Matthew Grossman, MD, a pediatric hospitalist at Yale New Haven Children’s Hospital, New Haven, Conn., who created Eat, Sleep, Console.

Dr. Grossman, associate professor and vice chair for quality in the department of pediatrics at Yale University, said he noticed that when mothers stayed overnight with their babies, the infants tended to have fewer withdrawal symptoms. Indeed, previous studies had demonstrated the benefits of breastfeeding and allowing mothers and babies to share a room.

“If you think of mom as a medicine, then you can’t put the baby in a unit where the mom can’t be there,” Dr. Grossman told this news organization. “It would be like taking a kid with pneumonia and putting him in a unit that doesn’t have antibiotics.”

Despite its prominence, the Finnegan score has never been validated for guiding the treatment of NAS. In addition, Finnegan scores can be inconsistent, and the assessment requires disturbing an infant to check signs such as its startle reflex, which, as Dr. Grossman and his fellow researchers pointed out, flies in the face of American Academy of Pediatrics’ recommendations to prioritize swaddling and minimize stimulation for infants with NAS.

By contrast, Eat, Sleep, Console offers a simplified assessment. Interventions are called for if a baby eats less than an ounce of food at a time/does not breastfeed, sleeps less than an hour at a stretch, or takes more than 10 minutes to be consoled. After nonpharmacologic interventions have been tried, doses of medication are used as needed. Babies who are doing well can be discharged in as few as 4 days.
 

Quashing bias against parents with substance abuse disorder

Even with the promise of shorter stays and better care, switching to nonpharmacologic care presents hurdles for hospitals. Among these is a lack of physical space for mothers to room with their babies in a quiet environment.

“In many community hospitals, the only place for infants to go is a neonatal intensive care unit, outside of the newborn nursery,” said Stephen Patrick, MD, MPH, associate professor and director of the Center for Child Health Policy at Vanderbilt University, Nashville, Tenn., who researches stigma associated with opioid use during pregnancy.

Administrators at SSM St. Mary’s Hospital in St. Louis initially balked at providing private rooms for mothers and their babies with NAS and NOWS, according to Kimberly Spence, MD, a neonatologist at SSM Health. She said the initial plan was to put the babies in a busy, brightly lit nursery.

But resistance waned as the hospital convinced health plans to pay for private rooms for the 5-7 days it typically takes a baby to go through withdrawal, said Dr. Spence, associate professor of pediatrics at Saint Louis University.

“We were able to provide enough data that this is evidence-based medicine and babies do better with their moms, and that ethically, this is the right thing to do, to reduce transfers to an NICU,” she said.

In addition, news stories about the family-centric approach and shorter stays for infants, along with SSM’s launch of an outpatient clinic to treat pregnant women with opioid use disorder, helped the system to attract more patients and increase its market share, said Dr. Spence.

Another challenge was getting physicians and nurses to set aside any judgments of parents with substance abuse disorder, according to Dr. Grossman and others.

“A lot of faculty and staff on the medical team didn’t feel like we should trust moms with their babies’ medical care” at SSM, Dr. Spence said.

Some hospitals conduct anti-bias training to teach providers that substance abuse is a disease that deserves proper medical treatment and not the moral failing of a patient. Such education may involve explaining that babies’ outcomes are improved when women undergo treatment with methadone or buprenorphine during pregnancy, even though use of those medications does pose a risk of NAS.

Creating a system that supports parents with substance abuse disorders may help to change perceptions. At Atrium Health, some staff members now enjoy working with these families because they can make a profound impact, Dr. Dodds said. He said they’ve learned that families suffering from substance abuse disorder “are not that different than any other family.”

Dr. Dodds, Dr. Patrick, Dr. Spence, and Dr. Grossman reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Four years ago, Atrium Health, in Charlotte, N.C., embarked on a dramatic change in how it cares for newborns exposed to opioids in the womb.

Until then, most of the 700 or so babies who underwent opioid withdrawal each year in the hospital system spent their first weeks in a neonatal intensive care unit (NICU), isolated from their parents and treated with regular doses of morphine to ease their symptoms.

Now, most babies stay in the hospital for just a few days under a new approach called Eat, Sleep, Console. These young patients stay in private rooms where they can bond with their parents and volunteer caregivers. The usual course of treatment is no longer extended therapy with opioid replacements. Instead, mothers are encouraged to stay overnight and are taught how to sooth their babies with swaddling, rocking, and cooing.

As a result, the average length of stay for newborns with neonatal abstinence syndrome (NAS) has dropped from 12 days to 6. Use of morphine has fallen by 79%, from 2.25 to 0.45 mg/kg per stay, according to results of a quality improvement pilot project at one of Atrium’s community hospitals.

Similar outcomes from other hospitals around the country have led to widespread uptake of Eat, Sleep, Console since its advent in 2017. That year, according to federal data, seven newborns were diagnosed with NAS for every 1,000 births.

Advocates say the family-centric model helps parents feel less stigmatized and more confident in their ability to care for their babies, who can have symptoms such as irritability and difficulty feeding for months.

The approach “really empowers families to do what they do best, which is take care of each other,” Douglas Dodds, MD, a pediatrician who led the effort at Atrium, told this news organization.
 

Questioning the old protocols

Numerous state perinatal collaboratives, hospital associations, and health systems say the program is the new standard of care for infants with NAS and neonatal opioid withdrawal syndrome (NOWS).

Twenty-six hospitals have adopted Eat, Sleep, Console as part of a clinical trial sponsored by the National Institutes of Health and a program called Advancing Clinical Trials in Neonatal Opioid Withdrawal Syndrome (ACT NOW). Researchers are comparing the approach to previous care protocols in regard to 12 outcomes, including time to medical readiness for discharge, frequency of opioid replacement therapy, and safety problems, such as seizures during treatment.

The transition has been swift. Less than a decade ago, most hospitals used the Finnegan Neonatal Abstinence Scoring System, which was developed in the 1970s to assess babies whose mothers had used heroin during pregnancy.

The Finnegan score entails monitoring babies every 3 hours for 21 symptoms, including high-pitched crying, sneezing, gastrointestinal problems, and yawning. If a baby scores an 8 or more three times in a row, most protocols using the traditional Finnegan approach recommend that providers move infants to an NICU, where they receive morphine or methadone. Once opioid replacement therapy is started, the protocols require a gradual weaning that lasts 3-4 weeks.

As the opioid epidemic grew and NICUs around the country began to fill with babies experiencing NAS or NOW, some clinicians began to question the Finnegan-driven approach.

“You have these miserable babies who are going through this really tough experience, and our first move is to separate them from their moms,” said Matthew Grossman, MD, a pediatric hospitalist at Yale New Haven Children’s Hospital, New Haven, Conn., who created Eat, Sleep, Console.

Dr. Grossman, associate professor and vice chair for quality in the department of pediatrics at Yale University, said he noticed that when mothers stayed overnight with their babies, the infants tended to have fewer withdrawal symptoms. Indeed, previous studies had demonstrated the benefits of breastfeeding and allowing mothers and babies to share a room.

“If you think of mom as a medicine, then you can’t put the baby in a unit where the mom can’t be there,” Dr. Grossman told this news organization. “It would be like taking a kid with pneumonia and putting him in a unit that doesn’t have antibiotics.”

Despite its prominence, the Finnegan score has never been validated for guiding the treatment of NAS. In addition, Finnegan scores can be inconsistent, and the assessment requires disturbing an infant to check signs such as its startle reflex, which, as Dr. Grossman and his fellow researchers pointed out, flies in the face of American Academy of Pediatrics’ recommendations to prioritize swaddling and minimize stimulation for infants with NAS.

By contrast, Eat, Sleep, Console offers a simplified assessment. Interventions are called for if a baby eats less than an ounce of food at a time/does not breastfeed, sleeps less than an hour at a stretch, or takes more than 10 minutes to be consoled. After nonpharmacologic interventions have been tried, doses of medication are used as needed. Babies who are doing well can be discharged in as few as 4 days.
 

Quashing bias against parents with substance abuse disorder

Even with the promise of shorter stays and better care, switching to nonpharmacologic care presents hurdles for hospitals. Among these is a lack of physical space for mothers to room with their babies in a quiet environment.

“In many community hospitals, the only place for infants to go is a neonatal intensive care unit, outside of the newborn nursery,” said Stephen Patrick, MD, MPH, associate professor and director of the Center for Child Health Policy at Vanderbilt University, Nashville, Tenn., who researches stigma associated with opioid use during pregnancy.

Administrators at SSM St. Mary’s Hospital in St. Louis initially balked at providing private rooms for mothers and their babies with NAS and NOWS, according to Kimberly Spence, MD, a neonatologist at SSM Health. She said the initial plan was to put the babies in a busy, brightly lit nursery.

But resistance waned as the hospital convinced health plans to pay for private rooms for the 5-7 days it typically takes a baby to go through withdrawal, said Dr. Spence, associate professor of pediatrics at Saint Louis University.

“We were able to provide enough data that this is evidence-based medicine and babies do better with their moms, and that ethically, this is the right thing to do, to reduce transfers to an NICU,” she said.

In addition, news stories about the family-centric approach and shorter stays for infants, along with SSM’s launch of an outpatient clinic to treat pregnant women with opioid use disorder, helped the system to attract more patients and increase its market share, said Dr. Spence.

Another challenge was getting physicians and nurses to set aside any judgments of parents with substance abuse disorder, according to Dr. Grossman and others.

“A lot of faculty and staff on the medical team didn’t feel like we should trust moms with their babies’ medical care” at SSM, Dr. Spence said.

Some hospitals conduct anti-bias training to teach providers that substance abuse is a disease that deserves proper medical treatment and not the moral failing of a patient. Such education may involve explaining that babies’ outcomes are improved when women undergo treatment with methadone or buprenorphine during pregnancy, even though use of those medications does pose a risk of NAS.

Creating a system that supports parents with substance abuse disorders may help to change perceptions. At Atrium Health, some staff members now enjoy working with these families because they can make a profound impact, Dr. Dodds said. He said they’ve learned that families suffering from substance abuse disorder “are not that different than any other family.”

Dr. Dodds, Dr. Patrick, Dr. Spence, and Dr. Grossman reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Opioid use in the elderly is associated with an almost 40% increased risk of dementia in new findings that suggest exposure to these drugs may be another modifiable risk factor for dementia.

“Clinicians and others may want to consider that opioid exposure in those aged 75-80 increases dementia risk, and to balance the potential benefits of opioid use in old age with adverse side effects,” said Stephen Z. Levine, PhD, professor, department of community mental health, University of Haifa (Israel).

The study was published online in the American Journal of Geriatric Psychiatry.
 

Widespread use

Evidence points to a relatively high rate of opioid prescriptions among older adults. A Morbidity and Mortality Weekly Report noted 19.2% of the U.S. adult population filled an opioid prescription in 2018, with the rate in those over 65 double that of adults aged 20-24 years (25% vs. 11.2%).

Disorders and illnesses for which opioids might be prescribed, including cancer and some pain conditions, “are far more prevalent in old age than at a younger age,” said Dr. Levine.

This high rate of opioid use underscores the need to consider the risks of opioid use in old age, said Dr. Levine. “Unfortunately, studies of the association between opioid use and dementia risk in old age are few, and their results are inconsistent.”

The study included 91,307 Israeli citizens aged 60 and over without dementia who were enrolled in the Meuhedet Healthcare Services, a nonprofit health maintenance organization (HMO) serving 14% of the country’s population. Meuhedet has maintained an up-to-date dementia registry since 2002.

The average age of the study sample was 68.29 years at the start of the study (in 2012).

In Israel, opioids are prescribed for a 30-day period. In this study, opioid exposure was defined as opioid medication fills covering 60 days (or two prescriptions) within a 120-day interval.

The primary outcome was incident dementia during follow-up from Jan. 1, 2013 to Oct. 30, 2017. The analysis controlled for a number of factors, including age, sex, smoking status, health conditions such as arthritis, depression, diabetes, osteoporosis, cognitive decline, vitamin deficiencies, cancer, cardiovascular conditions, and hospitalizations for falls.

Researchers also accounted for the competing risk of mortality.

During the study, 3.1% of subjects were exposed to opioids at a mean age of 73.94 years, and 5.8% of subjects developed dementia at an average age of 78.07 years.
 

Increased dementia risk

The risk of incident dementia was significantly increased in those exposed to opioids versus unexposed individuals in the 75- to 80-year age group (adjusted hazard ratio, 1.39; 95% confidence interval, 1.01-1.92; z statistic = 2.02; P < .05).

The authors noted the effect size for opioid exposure in this elderly age group is like other potentially modifiable risk factors for dementia, including body mass index and smoking.

The current study could not determine the biological explanation for the increased dementia risk among older opioid users. “Causal notions are challenging in observational studies and should be viewed with caution,” Dr. Levine noted.

However, a plausible mechanism highlighted in the literature is that opioids promote apoptosis of microglia and neurons that contribute to neurodegenerative diseases, he said.

The study included 14 sensitivity analyses, including those that looked at females, subjects older than 70, smokers, and groups with and without comorbid health conditions. The only sensitivity analysis that didn’t have similar findings to the primary analysis looked at dementia risk restricted to subjects without a vitamin deficiency.

“It’s reassuring that 13 or 14 sensitivity analyses found a significant association between opioid exposure and dementia risk,” said Dr. Levine.

Some prior studies did not show an association between opioid exposure and dementia risk. One possible reason for the discrepancy with the current findings is that the previous research didn’t account for age-specific opioid use effects, or the competing risk of mortality, said Dr. Levine.

Clinicians have a number of potential alternatives to opioids to treat various conditions including acetaminophen, non-steroidal anti-inflammatory drugs, amine reuptake inhibitors (ARIs), membrane stabilizers, muscle relaxants, topical capsaicin, botulinum toxin, cannabinoids, and steroids.

A limitation of the study was that it didn’t adjust for all possible comorbid health conditions, including vascular conditions, or for use of benzodiazepines, and surgical procedures.

In addition, since up to 50% of dementia cases are undetected, it’s possible some in the unexposed opioid group may actually have undiagnosed dementia, thereby reducing the effect sizes in the results.

Reverse causality is also a possibility as the neuropathological process associated with dementia could have started prior to opioid exposure. In addition, the results are limited to prolonged opioid exposure.
 

Interpret with caution

Commenting on the study, David Knopman, MD, a neurologist at Mayo Clinic in Rochester, Minn., whose research involves late-life cognitive disorders, was skeptical.

“On the face of it, the fact that an association was seen only in one narrow age range – 75+ to 80 years – ought to raise serious suspicion about the reliability and validity of the claim that opioid use is a risk factor for dementia, he said.

Although the researchers performed several sensitivity analyses, including accounting for mortality, “pharmacoepidemiological studies are terribly sensitive to residual biases” related to physician and patient choices related to medication use, added Dr. Knopman.

The claim that opioids are a dementia risk “should be viewed with great caution” and should not influence use of opioids where they’re truly indicated, he said.

“It would be a great pity if patients with pain requiring opioids avoid them because of fears about dementia based on the dubious relationship between age and opioid use.”

Dr. Levine and Dr. Knopman report no relevant financial disclosures.

A version of this article first appeared on Medscape.com.

Opioid use in the elderly is associated with an almost 40% increased risk of dementia in new findings that suggest exposure to these drugs may be another modifiable risk factor for dementia.

“Clinicians and others may want to consider that opioid exposure in those aged 75-80 increases dementia risk, and to balance the potential benefits of opioid use in old age with adverse side effects,” said Stephen Z. Levine, PhD, professor, department of community mental health, University of Haifa (Israel).

The study was published online in the American Journal of Geriatric Psychiatry.
 

Widespread use

Evidence points to a relatively high rate of opioid prescriptions among older adults. A Morbidity and Mortality Weekly Report noted 19.2% of the U.S. adult population filled an opioid prescription in 2018, with the rate in those over 65 double that of adults aged 20-24 years (25% vs. 11.2%).

Disorders and illnesses for which opioids might be prescribed, including cancer and some pain conditions, “are far more prevalent in old age than at a younger age,” said Dr. Levine.

This high rate of opioid use underscores the need to consider the risks of opioid use in old age, said Dr. Levine. “Unfortunately, studies of the association between opioid use and dementia risk in old age are few, and their results are inconsistent.”

The study included 91,307 Israeli citizens aged 60 and over without dementia who were enrolled in the Meuhedet Healthcare Services, a nonprofit health maintenance organization (HMO) serving 14% of the country’s population. Meuhedet has maintained an up-to-date dementia registry since 2002.

The average age of the study sample was 68.29 years at the start of the study (in 2012).

In Israel, opioids are prescribed for a 30-day period. In this study, opioid exposure was defined as opioid medication fills covering 60 days (or two prescriptions) within a 120-day interval.

The primary outcome was incident dementia during follow-up from Jan. 1, 2013 to Oct. 30, 2017. The analysis controlled for a number of factors, including age, sex, smoking status, health conditions such as arthritis, depression, diabetes, osteoporosis, cognitive decline, vitamin deficiencies, cancer, cardiovascular conditions, and hospitalizations for falls.

Researchers also accounted for the competing risk of mortality.

During the study, 3.1% of subjects were exposed to opioids at a mean age of 73.94 years, and 5.8% of subjects developed dementia at an average age of 78.07 years.
 

Increased dementia risk

The risk of incident dementia was significantly increased in those exposed to opioids versus unexposed individuals in the 75- to 80-year age group (adjusted hazard ratio, 1.39; 95% confidence interval, 1.01-1.92; z statistic = 2.02; P < .05).

The authors noted the effect size for opioid exposure in this elderly age group is like other potentially modifiable risk factors for dementia, including body mass index and smoking.

The current study could not determine the biological explanation for the increased dementia risk among older opioid users. “Causal notions are challenging in observational studies and should be viewed with caution,” Dr. Levine noted.

However, a plausible mechanism highlighted in the literature is that opioids promote apoptosis of microglia and neurons that contribute to neurodegenerative diseases, he said.

The study included 14 sensitivity analyses, including those that looked at females, subjects older than 70, smokers, and groups with and without comorbid health conditions. The only sensitivity analysis that didn’t have similar findings to the primary analysis looked at dementia risk restricted to subjects without a vitamin deficiency.

“It’s reassuring that 13 or 14 sensitivity analyses found a significant association between opioid exposure and dementia risk,” said Dr. Levine.

Some prior studies did not show an association between opioid exposure and dementia risk. One possible reason for the discrepancy with the current findings is that the previous research didn’t account for age-specific opioid use effects, or the competing risk of mortality, said Dr. Levine.

Clinicians have a number of potential alternatives to opioids to treat various conditions including acetaminophen, non-steroidal anti-inflammatory drugs, amine reuptake inhibitors (ARIs), membrane stabilizers, muscle relaxants, topical capsaicin, botulinum toxin, cannabinoids, and steroids.

A limitation of the study was that it didn’t adjust for all possible comorbid health conditions, including vascular conditions, or for use of benzodiazepines, and surgical procedures.

In addition, since up to 50% of dementia cases are undetected, it’s possible some in the unexposed opioid group may actually have undiagnosed dementia, thereby reducing the effect sizes in the results.

Reverse causality is also a possibility as the neuropathological process associated with dementia could have started prior to opioid exposure. In addition, the results are limited to prolonged opioid exposure.
 

Interpret with caution

Commenting on the study, David Knopman, MD, a neurologist at Mayo Clinic in Rochester, Minn., whose research involves late-life cognitive disorders, was skeptical.

“On the face of it, the fact that an association was seen only in one narrow age range – 75+ to 80 years – ought to raise serious suspicion about the reliability and validity of the claim that opioid use is a risk factor for dementia, he said.

Although the researchers performed several sensitivity analyses, including accounting for mortality, “pharmacoepidemiological studies are terribly sensitive to residual biases” related to physician and patient choices related to medication use, added Dr. Knopman.

The claim that opioids are a dementia risk “should be viewed with great caution” and should not influence use of opioids where they’re truly indicated, he said.

“It would be a great pity if patients with pain requiring opioids avoid them because of fears about dementia based on the dubious relationship between age and opioid use.”

Dr. Levine and Dr. Knopman report no relevant financial disclosures.

A version of this article first appeared on Medscape.com.

Opioid use in the elderly is associated with an almost 40% increased risk of dementia in new findings that suggest exposure to these drugs may be another modifiable risk factor for dementia.

“Clinicians and others may want to consider that opioid exposure in those aged 75-80 increases dementia risk, and to balance the potential benefits of opioid use in old age with adverse side effects,” said Stephen Z. Levine, PhD, professor, department of community mental health, University of Haifa (Israel).

The study was published online in the American Journal of Geriatric Psychiatry.
 

Widespread use

Evidence points to a relatively high rate of opioid prescriptions among older adults. A Morbidity and Mortality Weekly Report noted 19.2% of the U.S. adult population filled an opioid prescription in 2018, with the rate in those over 65 double that of adults aged 20-24 years (25% vs. 11.2%).

Disorders and illnesses for which opioids might be prescribed, including cancer and some pain conditions, “are far more prevalent in old age than at a younger age,” said Dr. Levine.

This high rate of opioid use underscores the need to consider the risks of opioid use in old age, said Dr. Levine. “Unfortunately, studies of the association between opioid use and dementia risk in old age are few, and their results are inconsistent.”

The study included 91,307 Israeli citizens aged 60 and over without dementia who were enrolled in the Meuhedet Healthcare Services, a nonprofit health maintenance organization (HMO) serving 14% of the country’s population. Meuhedet has maintained an up-to-date dementia registry since 2002.

The average age of the study sample was 68.29 years at the start of the study (in 2012).

In Israel, opioids are prescribed for a 30-day period. In this study, opioid exposure was defined as opioid medication fills covering 60 days (or two prescriptions) within a 120-day interval.

The primary outcome was incident dementia during follow-up from Jan. 1, 2013 to Oct. 30, 2017. The analysis controlled for a number of factors, including age, sex, smoking status, health conditions such as arthritis, depression, diabetes, osteoporosis, cognitive decline, vitamin deficiencies, cancer, cardiovascular conditions, and hospitalizations for falls.

Researchers also accounted for the competing risk of mortality.

During the study, 3.1% of subjects were exposed to opioids at a mean age of 73.94 years, and 5.8% of subjects developed dementia at an average age of 78.07 years.
 

Increased dementia risk

The risk of incident dementia was significantly increased in those exposed to opioids versus unexposed individuals in the 75- to 80-year age group (adjusted hazard ratio, 1.39; 95% confidence interval, 1.01-1.92; z statistic = 2.02; P < .05).

The authors noted the effect size for opioid exposure in this elderly age group is like other potentially modifiable risk factors for dementia, including body mass index and smoking.

The current study could not determine the biological explanation for the increased dementia risk among older opioid users. “Causal notions are challenging in observational studies and should be viewed with caution,” Dr. Levine noted.

However, a plausible mechanism highlighted in the literature is that opioids promote apoptosis of microglia and neurons that contribute to neurodegenerative diseases, he said.

The study included 14 sensitivity analyses, including those that looked at females, subjects older than 70, smokers, and groups with and without comorbid health conditions. The only sensitivity analysis that didn’t have similar findings to the primary analysis looked at dementia risk restricted to subjects without a vitamin deficiency.

“It’s reassuring that 13 or 14 sensitivity analyses found a significant association between opioid exposure and dementia risk,” said Dr. Levine.

Some prior studies did not show an association between opioid exposure and dementia risk. One possible reason for the discrepancy with the current findings is that the previous research didn’t account for age-specific opioid use effects, or the competing risk of mortality, said Dr. Levine.

Clinicians have a number of potential alternatives to opioids to treat various conditions including acetaminophen, non-steroidal anti-inflammatory drugs, amine reuptake inhibitors (ARIs), membrane stabilizers, muscle relaxants, topical capsaicin, botulinum toxin, cannabinoids, and steroids.

A limitation of the study was that it didn’t adjust for all possible comorbid health conditions, including vascular conditions, or for use of benzodiazepines, and surgical procedures.

In addition, since up to 50% of dementia cases are undetected, it’s possible some in the unexposed opioid group may actually have undiagnosed dementia, thereby reducing the effect sizes in the results.

Reverse causality is also a possibility as the neuropathological process associated with dementia could have started prior to opioid exposure. In addition, the results are limited to prolonged opioid exposure.
 

Interpret with caution

Commenting on the study, David Knopman, MD, a neurologist at Mayo Clinic in Rochester, Minn., whose research involves late-life cognitive disorders, was skeptical.

“On the face of it, the fact that an association was seen only in one narrow age range – 75+ to 80 years – ought to raise serious suspicion about the reliability and validity of the claim that opioid use is a risk factor for dementia, he said.

Although the researchers performed several sensitivity analyses, including accounting for mortality, “pharmacoepidemiological studies are terribly sensitive to residual biases” related to physician and patient choices related to medication use, added Dr. Knopman.

The claim that opioids are a dementia risk “should be viewed with great caution” and should not influence use of opioids where they’re truly indicated, he said.

“It would be a great pity if patients with pain requiring opioids avoid them because of fears about dementia based on the dubious relationship between age and opioid use.”

Dr. Levine and Dr. Knopman report no relevant financial disclosures.

A version of this article first appeared on Medscape.com.

A group of clinicians is hoping to prompt a rethink of how opioids are prescribed to new mothers after cesarean deliveries after finding that sending patients home with smaller prescriptions led to dramatic drops in use of the drugs.

In research scheduled to be presented at the annual meeting of the American College of Obstetricians and Gynecologists (ACOG) in San Diego, women undergoing cesarean delivery were randomly assigned to receive prescriptions for either 10 or 20 oxycodone tablets at discharge. Interim data revealed that not only did 10-tablet prescriptions correlate with significantly less opioid consumption, but 35% of all women left their opioid scripts unfilled.

The results suggest physicians should stop “automatically prescribing opioids for caesarean section patients at discharge and, instead, work on individualized prescribing,” said Amanda Selk, MD, associate professor of obstetrics and gynecology at the University of Toronto, who was not involved with the study.  

“We need to move away from a culture that says a patient can’t be discharged without an opioid prescription,” Dr. Selk said in an interview.

For the study, researchers at Virginia Tech Carilion School of Medicine, Roanoke, Virginia, set out to understand how discharge opioid prescription sizes impact opioid consumption in women who undergo caesarean delivery. Other specialties have found a correlation between the two.

With “no standard dose recommendation for physicians to follow when it came to prescribing opioids for post-cesarean pain management,” they also wanted to help their own clinicians optimize their prescribing, co-investigator Jaclyn Nunziato, MD, assistant professor of obstetrics and gynecology at Virginia Tech Carilion, told this news organization.

They randomly assigned 134 women undergoing a scheduled cesarean delivery to receive a prescription for 10 or 20 tablets of 5 mg oxycodone at discharge. Most women had one or more previous cesarean deliveries, and none had used opioids in the previous 30 days.

Data from 97 patients presented at the ACOG meeting showed that 35% of women had not filled their opioid prescriptions 6 weeks after surgery. For those who did fill the orders, the average consumption at week 6 of the study was 6.6 tablets in the 10-tablet group and 13.3 tablets in the 20-tablet group (P = .0005), according to the researchers. No patients in either group had requested a refill of their opioid medication.

Despite differences in opioid use, both groups reported similar pain scores throughout the study period, and almost all patients in both groups said they were satisfied with their pain management, the investigators reported.

With an average of 9.2 tablets consumed in the two groups combined, the findings indicate “a standard prescription of 10 tablets may be adequate to manage most patients’ postoperative pain,” Dr. Nunziato said.   

She said she hoped the results help change how physicians view the treatment of post-cesarean pain and also help “break down the stigma that opioids are the best treatment option for patients.”
 

Potential for ‘huge’ benefit

Given the number of cesarean deliveries performed every year in the United States – more than 1.1 million in 2020, according to the U.S. Centers for Disease Control and Prevention – providing smaller post-cesarean opioid prescriptions would be “hugely beneficial to individual patients and our larger community,” said Robyn Goodrich, a medical student at Virginia Tech and the first author of the study.

“The patient would receive an amount that is adequate for controlling their pain and keeping them comfortable but does not put them at risk of developing tolerance and addiction,” she added. “For the community, it reduces the number of prescription opioids that are left over and may be diverted or misused if not properly disposed of.”

Dr. Selk pointed to her own group’s randomized controlled trial, showing that post-cesarean patients who do not receive opioids for pain while in the hospital also do not ask for opioid prescriptions after discharge and that their pain can be well-managed with acetaminophen and nonsteroidal anti-inflammatory drugs.  

Dr. Selk, Dr. Nunziato, and Ms. Goodrich have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A group of clinicians is hoping to prompt a rethink of how opioids are prescribed to new mothers after cesarean deliveries after finding that sending patients home with smaller prescriptions led to dramatic drops in use of the drugs.

In research scheduled to be presented at the annual meeting of the American College of Obstetricians and Gynecologists (ACOG) in San Diego, women undergoing cesarean delivery were randomly assigned to receive prescriptions for either 10 or 20 oxycodone tablets at discharge. Interim data revealed that not only did 10-tablet prescriptions correlate with significantly less opioid consumption, but 35% of all women left their opioid scripts unfilled.

The results suggest physicians should stop “automatically prescribing opioids for caesarean section patients at discharge and, instead, work on individualized prescribing,” said Amanda Selk, MD, associate professor of obstetrics and gynecology at the University of Toronto, who was not involved with the study.  

“We need to move away from a culture that says a patient can’t be discharged without an opioid prescription,” Dr. Selk said in an interview.

For the study, researchers at Virginia Tech Carilion School of Medicine, Roanoke, Virginia, set out to understand how discharge opioid prescription sizes impact opioid consumption in women who undergo caesarean delivery. Other specialties have found a correlation between the two.

With “no standard dose recommendation for physicians to follow when it came to prescribing opioids for post-cesarean pain management,” they also wanted to help their own clinicians optimize their prescribing, co-investigator Jaclyn Nunziato, MD, assistant professor of obstetrics and gynecology at Virginia Tech Carilion, told this news organization.

They randomly assigned 134 women undergoing a scheduled cesarean delivery to receive a prescription for 10 or 20 tablets of 5 mg oxycodone at discharge. Most women had one or more previous cesarean deliveries, and none had used opioids in the previous 30 days.

Data from 97 patients presented at the ACOG meeting showed that 35% of women had not filled their opioid prescriptions 6 weeks after surgery. For those who did fill the orders, the average consumption at week 6 of the study was 6.6 tablets in the 10-tablet group and 13.3 tablets in the 20-tablet group (P = .0005), according to the researchers. No patients in either group had requested a refill of their opioid medication.

Despite differences in opioid use, both groups reported similar pain scores throughout the study period, and almost all patients in both groups said they were satisfied with their pain management, the investigators reported.

With an average of 9.2 tablets consumed in the two groups combined, the findings indicate “a standard prescription of 10 tablets may be adequate to manage most patients’ postoperative pain,” Dr. Nunziato said.   

She said she hoped the results help change how physicians view the treatment of post-cesarean pain and also help “break down the stigma that opioids are the best treatment option for patients.”
 

Potential for ‘huge’ benefit

Given the number of cesarean deliveries performed every year in the United States – more than 1.1 million in 2020, according to the U.S. Centers for Disease Control and Prevention – providing smaller post-cesarean opioid prescriptions would be “hugely beneficial to individual patients and our larger community,” said Robyn Goodrich, a medical student at Virginia Tech and the first author of the study.

“The patient would receive an amount that is adequate for controlling their pain and keeping them comfortable but does not put them at risk of developing tolerance and addiction,” she added. “For the community, it reduces the number of prescription opioids that are left over and may be diverted or misused if not properly disposed of.”

Dr. Selk pointed to her own group’s randomized controlled trial, showing that post-cesarean patients who do not receive opioids for pain while in the hospital also do not ask for opioid prescriptions after discharge and that their pain can be well-managed with acetaminophen and nonsteroidal anti-inflammatory drugs.  

Dr. Selk, Dr. Nunziato, and Ms. Goodrich have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A group of clinicians is hoping to prompt a rethink of how opioids are prescribed to new mothers after cesarean deliveries after finding that sending patients home with smaller prescriptions led to dramatic drops in use of the drugs.

In research scheduled to be presented at the annual meeting of the American College of Obstetricians and Gynecologists (ACOG) in San Diego, women undergoing cesarean delivery were randomly assigned to receive prescriptions for either 10 or 20 oxycodone tablets at discharge. Interim data revealed that not only did 10-tablet prescriptions correlate with significantly less opioid consumption, but 35% of all women left their opioid scripts unfilled.

The results suggest physicians should stop “automatically prescribing opioids for caesarean section patients at discharge and, instead, work on individualized prescribing,” said Amanda Selk, MD, associate professor of obstetrics and gynecology at the University of Toronto, who was not involved with the study.  

“We need to move away from a culture that says a patient can’t be discharged without an opioid prescription,” Dr. Selk said in an interview.

For the study, researchers at Virginia Tech Carilion School of Medicine, Roanoke, Virginia, set out to understand how discharge opioid prescription sizes impact opioid consumption in women who undergo caesarean delivery. Other specialties have found a correlation between the two.

With “no standard dose recommendation for physicians to follow when it came to prescribing opioids for post-cesarean pain management,” they also wanted to help their own clinicians optimize their prescribing, co-investigator Jaclyn Nunziato, MD, assistant professor of obstetrics and gynecology at Virginia Tech Carilion, told this news organization.

They randomly assigned 134 women undergoing a scheduled cesarean delivery to receive a prescription for 10 or 20 tablets of 5 mg oxycodone at discharge. Most women had one or more previous cesarean deliveries, and none had used opioids in the previous 30 days.

Data from 97 patients presented at the ACOG meeting showed that 35% of women had not filled their opioid prescriptions 6 weeks after surgery. For those who did fill the orders, the average consumption at week 6 of the study was 6.6 tablets in the 10-tablet group and 13.3 tablets in the 20-tablet group (P = .0005), according to the researchers. No patients in either group had requested a refill of their opioid medication.

Despite differences in opioid use, both groups reported similar pain scores throughout the study period, and almost all patients in both groups said they were satisfied with their pain management, the investigators reported.

With an average of 9.2 tablets consumed in the two groups combined, the findings indicate “a standard prescription of 10 tablets may be adequate to manage most patients’ postoperative pain,” Dr. Nunziato said.   

She said she hoped the results help change how physicians view the treatment of post-cesarean pain and also help “break down the stigma that opioids are the best treatment option for patients.”
 

Potential for ‘huge’ benefit

Given the number of cesarean deliveries performed every year in the United States – more than 1.1 million in 2020, according to the U.S. Centers for Disease Control and Prevention – providing smaller post-cesarean opioid prescriptions would be “hugely beneficial to individual patients and our larger community,” said Robyn Goodrich, a medical student at Virginia Tech and the first author of the study.

“The patient would receive an amount that is adequate for controlling their pain and keeping them comfortable but does not put them at risk of developing tolerance and addiction,” she added. “For the community, it reduces the number of prescription opioids that are left over and may be diverted or misused if not properly disposed of.”

Dr. Selk pointed to her own group’s randomized controlled trial, showing that post-cesarean patients who do not receive opioids for pain while in the hospital also do not ask for opioid prescriptions after discharge and that their pain can be well-managed with acetaminophen and nonsteroidal anti-inflammatory drugs.  

Dr. Selk, Dr. Nunziato, and Ms. Goodrich have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The number of overdose deaths in adolescents nearly doubled in 2020 from the year before and increased substantially again in 2021 after nearly a decade of fairly stable rates, according to data published in a JAMA research letter.

Most of the deaths involved fentanyl, the researchers found.

Joseph Friedman, MPH, of the Center for Social Medicine and Humanities at the University of California, Los Angeles, led the study, which analyzed adolescent (14-18 years old) overdose deaths in the United States from 2010 to June 2021 in light of increasing contamination in the supply of illicit drugs.

The researchers found there were 518 deaths among adolescents (2.40 per 100,000 population) in 2010, and the rates remained stable through 2019 with 492 deaths (2.36 per 100,000).

In 2020, however, deaths spiked to 954 (4.57 per 100 000), increasing by 94.3%, compared with 2019. In 2021, they increased another 20%.

The rise in fentanyl-involved deaths was particularly striking. Fentanyl-involved deaths increased from 253 (1.21 per 100,000) in 2019 to 680 (3.26 per 100,000) in 2020. The numbers through June 2021 were annualized for 2021 and calculations predicted 884 deaths (4.23 per 100,000) for the year.
 

Numbers point to fentanyl potency

In 2021, more than three-fourths (77.14%) of adolescent overdose deaths involved fentanyl, compared with 13.26% for benzodiazepines, 9.77% for methamphetamine, 7.33% for cocaine, 5.76% for prescription opioids, and 2.27% for heroin.

American Indian and Alaska Native adolescents had the highest overdose rate in 2021 (n = 24; 11.79 per 100,000), followed by Latinx adolescents (n = 354; 6.98 per 100,000).

“These adolescent trends fit a wider pattern of increasing racial and ethnic inequalities in overdose that deserve further investigation and intervention efforts,” the authors wrote.
 

Pandemic’s role unclear

The spikes in adolescent overdoses overlap the COVID-19 pandemic, but Dr. Friedman said in an interview the pandemic “may or may not have been a big factor. “

The authors wrote that drug use had generally been stable among adolescents between 2010 and 2020. The number of 10th graders reporting any illicit drug use was 30.2% in 2010 and 30.4% in 2020.

“So it’s not that more teens are using drugs. It’s just that drug use is becoming more dangerous due to the spread of counterfeit pills containing fentanyls,” Dr. Friedman said.

The authors noted that “the illicit drug supply has increasingly become contaminated with illicitly manufactured fentanyls and other synthetic opioid and benzodiazepine analogues.”

Mr. Friedman said the pandemic may have accelerated the spread of more dangerous forms of drugs as supply chains were disrupted.

Benjamin Brady, DrPH, an assistant professor at the University of Arizona, Tucson, who also has an appointment in the university’s Comprehensive Pain and Addiction Center, said in an interview the numbers that Dr. Friedman and colleagues present represent “worst fears coming true.”

He said he and his colleagues in the field “were anticipating a rise in overdose deaths for the next 5-10 years because of the way the supply-and-demand environment exists in the U.S.”

Dr. Brady explained that restricting access to prescription opioids has had an unfortunate side effect in decreasing access to a safer supply of drugs.

“Without having solutions that would reduce demand at the same rate, supply of the safer form of the drug has been reduced; that has pushed people toward heroin and street drugs and from 2016 on those have been adulterated with fentanyl,” he said.

He said the United States, compared with other developed nations, has been slower to embrace longer-term harm-reduction strategies and to improve access to treatment and care.

COVID likely also has exacerbated the problem in terms of isolation and reduction in quality of life that has adolescents seeking to fill that void with drugs, Dr. Brady said. They may be completely unaware that the drugs they are seeking are commonly cut with counterfeit fentanyl.

“Fentanyl can be up to 50 times stronger than heroin,” he noted. “Even just a little bit of fentanyl dramatically changes the risk profile on an overdose.”

Increasing rates of mental health concerns among adolescents over decades also contribute to drug-seeking trends, Dr. Brady noted.
 

Overdose increases in the overall population were smaller

In the overall population, the percentage increases were not nearly as large in 2020 and 2021 as they were for adolescents.

Rates of overdose deaths in the overall population increased steadily from 2010 and reached 70,630 in 2019. In 2020, the deaths increased to 91,799 (an increase of 29.48% from 2019) and increased 11.48% in 2021.

The researchers analyzed numbers from the Centers for Disease Control and Prevention WONDER (Wide-Ranging Online Data for Epidemiologic Research) database, which has records of all U.S. deaths for which drug overdose was listed as the underlying cause.

The authors and Dr. Brady report no relevant financial relationships.

The number of overdose deaths in adolescents nearly doubled in 2020 from the year before and increased substantially again in 2021 after nearly a decade of fairly stable rates, according to data published in a JAMA research letter.

Most of the deaths involved fentanyl, the researchers found.

Joseph Friedman, MPH, of the Center for Social Medicine and Humanities at the University of California, Los Angeles, led the study, which analyzed adolescent (14-18 years old) overdose deaths in the United States from 2010 to June 2021 in light of increasing contamination in the supply of illicit drugs.

The researchers found there were 518 deaths among adolescents (2.40 per 100,000 population) in 2010, and the rates remained stable through 2019 with 492 deaths (2.36 per 100,000).

In 2020, however, deaths spiked to 954 (4.57 per 100 000), increasing by 94.3%, compared with 2019. In 2021, they increased another 20%.

The rise in fentanyl-involved deaths was particularly striking. Fentanyl-involved deaths increased from 253 (1.21 per 100,000) in 2019 to 680 (3.26 per 100,000) in 2020. The numbers through June 2021 were annualized for 2021 and calculations predicted 884 deaths (4.23 per 100,000) for the year.
 

Numbers point to fentanyl potency

In 2021, more than three-fourths (77.14%) of adolescent overdose deaths involved fentanyl, compared with 13.26% for benzodiazepines, 9.77% for methamphetamine, 7.33% for cocaine, 5.76% for prescription opioids, and 2.27% for heroin.

American Indian and Alaska Native adolescents had the highest overdose rate in 2021 (n = 24; 11.79 per 100,000), followed by Latinx adolescents (n = 354; 6.98 per 100,000).

“These adolescent trends fit a wider pattern of increasing racial and ethnic inequalities in overdose that deserve further investigation and intervention efforts,” the authors wrote.
 

Pandemic’s role unclear

The spikes in adolescent overdoses overlap the COVID-19 pandemic, but Dr. Friedman said in an interview the pandemic “may or may not have been a big factor. “

The authors wrote that drug use had generally been stable among adolescents between 2010 and 2020. The number of 10th graders reporting any illicit drug use was 30.2% in 2010 and 30.4% in 2020.

“So it’s not that more teens are using drugs. It’s just that drug use is becoming more dangerous due to the spread of counterfeit pills containing fentanyls,” Dr. Friedman said.

The authors noted that “the illicit drug supply has increasingly become contaminated with illicitly manufactured fentanyls and other synthetic opioid and benzodiazepine analogues.”

Mr. Friedman said the pandemic may have accelerated the spread of more dangerous forms of drugs as supply chains were disrupted.

Benjamin Brady, DrPH, an assistant professor at the University of Arizona, Tucson, who also has an appointment in the university’s Comprehensive Pain and Addiction Center, said in an interview the numbers that Dr. Friedman and colleagues present represent “worst fears coming true.”

He said he and his colleagues in the field “were anticipating a rise in overdose deaths for the next 5-10 years because of the way the supply-and-demand environment exists in the U.S.”

Dr. Brady explained that restricting access to prescription opioids has had an unfortunate side effect in decreasing access to a safer supply of drugs.

“Without having solutions that would reduce demand at the same rate, supply of the safer form of the drug has been reduced; that has pushed people toward heroin and street drugs and from 2016 on those have been adulterated with fentanyl,” he said.

He said the United States, compared with other developed nations, has been slower to embrace longer-term harm-reduction strategies and to improve access to treatment and care.

COVID likely also has exacerbated the problem in terms of isolation and reduction in quality of life that has adolescents seeking to fill that void with drugs, Dr. Brady said. They may be completely unaware that the drugs they are seeking are commonly cut with counterfeit fentanyl.

“Fentanyl can be up to 50 times stronger than heroin,” he noted. “Even just a little bit of fentanyl dramatically changes the risk profile on an overdose.”

Increasing rates of mental health concerns among adolescents over decades also contribute to drug-seeking trends, Dr. Brady noted.
 

Overdose increases in the overall population were smaller

In the overall population, the percentage increases were not nearly as large in 2020 and 2021 as they were for adolescents.

Rates of overdose deaths in the overall population increased steadily from 2010 and reached 70,630 in 2019. In 2020, the deaths increased to 91,799 (an increase of 29.48% from 2019) and increased 11.48% in 2021.

The researchers analyzed numbers from the Centers for Disease Control and Prevention WONDER (Wide-Ranging Online Data for Epidemiologic Research) database, which has records of all U.S. deaths for which drug overdose was listed as the underlying cause.

The authors and Dr. Brady report no relevant financial relationships.

The number of overdose deaths in adolescents nearly doubled in 2020 from the year before and increased substantially again in 2021 after nearly a decade of fairly stable rates, according to data published in a JAMA research letter.

Most of the deaths involved fentanyl, the researchers found.

Joseph Friedman, MPH, of the Center for Social Medicine and Humanities at the University of California, Los Angeles, led the study, which analyzed adolescent (14-18 years old) overdose deaths in the United States from 2010 to June 2021 in light of increasing contamination in the supply of illicit drugs.

The researchers found there were 518 deaths among adolescents (2.40 per 100,000 population) in 2010, and the rates remained stable through 2019 with 492 deaths (2.36 per 100,000).

In 2020, however, deaths spiked to 954 (4.57 per 100 000), increasing by 94.3%, compared with 2019. In 2021, they increased another 20%.

The rise in fentanyl-involved deaths was particularly striking. Fentanyl-involved deaths increased from 253 (1.21 per 100,000) in 2019 to 680 (3.26 per 100,000) in 2020. The numbers through June 2021 were annualized for 2021 and calculations predicted 884 deaths (4.23 per 100,000) for the year.
 

Numbers point to fentanyl potency

In 2021, more than three-fourths (77.14%) of adolescent overdose deaths involved fentanyl, compared with 13.26% for benzodiazepines, 9.77% for methamphetamine, 7.33% for cocaine, 5.76% for prescription opioids, and 2.27% for heroin.

American Indian and Alaska Native adolescents had the highest overdose rate in 2021 (n = 24; 11.79 per 100,000), followed by Latinx adolescents (n = 354; 6.98 per 100,000).

“These adolescent trends fit a wider pattern of increasing racial and ethnic inequalities in overdose that deserve further investigation and intervention efforts,” the authors wrote.
 

Pandemic’s role unclear

The spikes in adolescent overdoses overlap the COVID-19 pandemic, but Dr. Friedman said in an interview the pandemic “may or may not have been a big factor. “

The authors wrote that drug use had generally been stable among adolescents between 2010 and 2020. The number of 10th graders reporting any illicit drug use was 30.2% in 2010 and 30.4% in 2020.

“So it’s not that more teens are using drugs. It’s just that drug use is becoming more dangerous due to the spread of counterfeit pills containing fentanyls,” Dr. Friedman said.

The authors noted that “the illicit drug supply has increasingly become contaminated with illicitly manufactured fentanyls and other synthetic opioid and benzodiazepine analogues.”

Mr. Friedman said the pandemic may have accelerated the spread of more dangerous forms of drugs as supply chains were disrupted.

Benjamin Brady, DrPH, an assistant professor at the University of Arizona, Tucson, who also has an appointment in the university’s Comprehensive Pain and Addiction Center, said in an interview the numbers that Dr. Friedman and colleagues present represent “worst fears coming true.”

He said he and his colleagues in the field “were anticipating a rise in overdose deaths for the next 5-10 years because of the way the supply-and-demand environment exists in the U.S.”

Dr. Brady explained that restricting access to prescription opioids has had an unfortunate side effect in decreasing access to a safer supply of drugs.

“Without having solutions that would reduce demand at the same rate, supply of the safer form of the drug has been reduced; that has pushed people toward heroin and street drugs and from 2016 on those have been adulterated with fentanyl,” he said.

He said the United States, compared with other developed nations, has been slower to embrace longer-term harm-reduction strategies and to improve access to treatment and care.

COVID likely also has exacerbated the problem in terms of isolation and reduction in quality of life that has adolescents seeking to fill that void with drugs, Dr. Brady said. They may be completely unaware that the drugs they are seeking are commonly cut with counterfeit fentanyl.

“Fentanyl can be up to 50 times stronger than heroin,” he noted. “Even just a little bit of fentanyl dramatically changes the risk profile on an overdose.”

Increasing rates of mental health concerns among adolescents over decades also contribute to drug-seeking trends, Dr. Brady noted.
 

Overdose increases in the overall population were smaller

In the overall population, the percentage increases were not nearly as large in 2020 and 2021 as they were for adolescents.

Rates of overdose deaths in the overall population increased steadily from 2010 and reached 70,630 in 2019. In 2020, the deaths increased to 91,799 (an increase of 29.48% from 2019) and increased 11.48% in 2021.

The researchers analyzed numbers from the Centers for Disease Control and Prevention WONDER (Wide-Ranging Online Data for Epidemiologic Research) database, which has records of all U.S. deaths for which drug overdose was listed as the underlying cause.

The authors and Dr. Brady report no relevant financial relationships.

Despite the availability of effective direct-acting antivirals, very few a mothers with opioid use disorder (OUD) and hepatitis C virus (HCV) during pregnancy received follow-up care or treatment for the infection within 6 months of giving birth, a retrospective study of Medicaid maternity patients found.

The study pooled data on 23,780 Medicaid-enrolled pregnant women with OUD who had a live or stillbirth during 2016-2019 and were followed for 6 months after delivery. Among these women – drawn from six states in the Medicaid Outcomes Distributed Research Network – the pooled average probability of HCV testing during pregnancy was 70.3% (95% confidence interval, 61.5%-79.1%). Of these, 30.9% (95% CI, 23.8%-38%) tested positive. At 60 days postpartum, just 3.2% (95% CI, 2.6%-3.8%) had a follow-up visit or treatment for HCV. In a subset of patients followed for 6 months, only 5.9% (95% CI, 4.9%-6.9%) had any HCV follow-up visit or medication within 6 months of delivery.

While HCV screening and diagnosis rates varied across states, postpartum follow-up rates were universally low. The results suggest a need to improve the cascade of postpartum care for HCV and, ultimately perhaps, introduce antenatal HCV treatment, as is currently given safely for HIV, if current clinical research establishes safety, according to Marian P. Jarlenski, PhD, MPH, an associate professor of public health policy and management at the University of Pittsburgh. The study was published in Obstetrics & Gynecology.

HCV infection has risen substantially in people of reproductive age in tandem with an increase in OUDs. HCV is transmitted from an infected mother to her baby in about 6% of cases, according to the Centers for Disease Control and Prevention, which in 2020 expanded its HCV screening recommendations to include all pregnant women. Currently no treatment for HCV during pregnancy has been approved.

In light of those recent recommendations, Dr. Jarlenski said in an interview that her group was “interested in looking at high-risk screened people and estimating what proportion received follow-up care and treatment for HCV. What is the promise of screening? The promise is that you can treat. Otherwise why screen?”

She acknowledged, however, that the postpartum period is a challenging time for a mother to seek health information or care for herself, whether she’s a new parent or has other children in the home. Nevertheless, the low rate of follow-up and treatment was unexpected. “Even the 70% rate of screening was low – we felt it should have been closer to 100% – but the follow-up rate was surprisingly low,” Dr. Jarlenski said.

Mishka Terplan, MD, MPH, medical director of Friends Research Institute in Baltimore, was not surprised at the low follow-up rate. “The cascade of care for hep C is demoralizing,” said Dr. Terplan, who was not involved in the study. “We know that hep C is syndemic with OUD and other opioid crises and we know that screening is effective for identifying hep C and that antiviral medications are now more effective and less toxic than ever before. But despite this, we’re failing pregnant women and their kids at every step along the cascade. We do a better job with initial testing than with the follow-up testing. We do a horrible job with postpartum medication initiation.”

He pointed to the systemic challenges mothers face in getting postpartum HCV care. “They may be transferred to a subspecialist for treatment, and this transfer is compounded by issues of insurance coverage and eligibility.” With the onus on new mothers to submit the paperwork, “the idea that mothers would be able to initiate much less continue postpartum treatment is absurd,” Dr. Terplan said.

He added that the children born to HCV-positive mothers need surveillance as well, but data suggest that the rates of newborn testing are also low. “There’s a preventable public health burden in all of this.”

The obvious way to increase eradicative therapy would be to treat women while they are getting antenatal care. A small phase 1 trial found that all pregnant participants who were HCV positive and given antivirals in their second trimester were safely treated and gave birth to healthy babies.

“If larger trials prove this treatment is safe and effective, then these results should be communicated to care providers and pregnant patients,” Dr. Jarlenski said. Otherwise, the public health potential of universal screening in pregnancy will not be realized.

This research was supported by the National Institute of Drug Abuse and by the Delaware Division of Medicaid and Medical Assistance and the University of Delaware, Center for Community Research & Service. Dr. Jarlenski disclosed no competing interests. One coauthor disclosed grant funding through her institution from Gilead Sciences and Organon unrelated to this work. Dr. Terplan reported no relevant competing interests.

Despite the availability of effective direct-acting antivirals, very few a mothers with opioid use disorder (OUD) and hepatitis C virus (HCV) during pregnancy received follow-up care or treatment for the infection within 6 months of giving birth, a retrospective study of Medicaid maternity patients found.

The study pooled data on 23,780 Medicaid-enrolled pregnant women with OUD who had a live or stillbirth during 2016-2019 and were followed for 6 months after delivery. Among these women – drawn from six states in the Medicaid Outcomes Distributed Research Network – the pooled average probability of HCV testing during pregnancy was 70.3% (95% confidence interval, 61.5%-79.1%). Of these, 30.9% (95% CI, 23.8%-38%) tested positive. At 60 days postpartum, just 3.2% (95% CI, 2.6%-3.8%) had a follow-up visit or treatment for HCV. In a subset of patients followed for 6 months, only 5.9% (95% CI, 4.9%-6.9%) had any HCV follow-up visit or medication within 6 months of delivery.

While HCV screening and diagnosis rates varied across states, postpartum follow-up rates were universally low. The results suggest a need to improve the cascade of postpartum care for HCV and, ultimately perhaps, introduce antenatal HCV treatment, as is currently given safely for HIV, if current clinical research establishes safety, according to Marian P. Jarlenski, PhD, MPH, an associate professor of public health policy and management at the University of Pittsburgh. The study was published in Obstetrics & Gynecology.

HCV infection has risen substantially in people of reproductive age in tandem with an increase in OUDs. HCV is transmitted from an infected mother to her baby in about 6% of cases, according to the Centers for Disease Control and Prevention, which in 2020 expanded its HCV screening recommendations to include all pregnant women. Currently no treatment for HCV during pregnancy has been approved.

In light of those recent recommendations, Dr. Jarlenski said in an interview that her group was “interested in looking at high-risk screened people and estimating what proportion received follow-up care and treatment for HCV. What is the promise of screening? The promise is that you can treat. Otherwise why screen?”

She acknowledged, however, that the postpartum period is a challenging time for a mother to seek health information or care for herself, whether she’s a new parent or has other children in the home. Nevertheless, the low rate of follow-up and treatment was unexpected. “Even the 70% rate of screening was low – we felt it should have been closer to 100% – but the follow-up rate was surprisingly low,” Dr. Jarlenski said.

Mishka Terplan, MD, MPH, medical director of Friends Research Institute in Baltimore, was not surprised at the low follow-up rate. “The cascade of care for hep C is demoralizing,” said Dr. Terplan, who was not involved in the study. “We know that hep C is syndemic with OUD and other opioid crises and we know that screening is effective for identifying hep C and that antiviral medications are now more effective and less toxic than ever before. But despite this, we’re failing pregnant women and their kids at every step along the cascade. We do a better job with initial testing than with the follow-up testing. We do a horrible job with postpartum medication initiation.”

He pointed to the systemic challenges mothers face in getting postpartum HCV care. “They may be transferred to a subspecialist for treatment, and this transfer is compounded by issues of insurance coverage and eligibility.” With the onus on new mothers to submit the paperwork, “the idea that mothers would be able to initiate much less continue postpartum treatment is absurd,” Dr. Terplan said.

He added that the children born to HCV-positive mothers need surveillance as well, but data suggest that the rates of newborn testing are also low. “There’s a preventable public health burden in all of this.”

The obvious way to increase eradicative therapy would be to treat women while they are getting antenatal care. A small phase 1 trial found that all pregnant participants who were HCV positive and given antivirals in their second trimester were safely treated and gave birth to healthy babies.

“If larger trials prove this treatment is safe and effective, then these results should be communicated to care providers and pregnant patients,” Dr. Jarlenski said. Otherwise, the public health potential of universal screening in pregnancy will not be realized.

This research was supported by the National Institute of Drug Abuse and by the Delaware Division of Medicaid and Medical Assistance and the University of Delaware, Center for Community Research & Service. Dr. Jarlenski disclosed no competing interests. One coauthor disclosed grant funding through her institution from Gilead Sciences and Organon unrelated to this work. Dr. Terplan reported no relevant competing interests.

Despite the availability of effective direct-acting antivirals, very few a mothers with opioid use disorder (OUD) and hepatitis C virus (HCV) during pregnancy received follow-up care or treatment for the infection within 6 months of giving birth, a retrospective study of Medicaid maternity patients found.

The study pooled data on 23,780 Medicaid-enrolled pregnant women with OUD who had a live or stillbirth during 2016-2019 and were followed for 6 months after delivery. Among these women – drawn from six states in the Medicaid Outcomes Distributed Research Network – the pooled average probability of HCV testing during pregnancy was 70.3% (95% confidence interval, 61.5%-79.1%). Of these, 30.9% (95% CI, 23.8%-38%) tested positive. At 60 days postpartum, just 3.2% (95% CI, 2.6%-3.8%) had a follow-up visit or treatment for HCV. In a subset of patients followed for 6 months, only 5.9% (95% CI, 4.9%-6.9%) had any HCV follow-up visit or medication within 6 months of delivery.

While HCV screening and diagnosis rates varied across states, postpartum follow-up rates were universally low. The results suggest a need to improve the cascade of postpartum care for HCV and, ultimately perhaps, introduce antenatal HCV treatment, as is currently given safely for HIV, if current clinical research establishes safety, according to Marian P. Jarlenski, PhD, MPH, an associate professor of public health policy and management at the University of Pittsburgh. The study was published in Obstetrics & Gynecology.

HCV infection has risen substantially in people of reproductive age in tandem with an increase in OUDs. HCV is transmitted from an infected mother to her baby in about 6% of cases, according to the Centers for Disease Control and Prevention, which in 2020 expanded its HCV screening recommendations to include all pregnant women. Currently no treatment for HCV during pregnancy has been approved.

In light of those recent recommendations, Dr. Jarlenski said in an interview that her group was “interested in looking at high-risk screened people and estimating what proportion received follow-up care and treatment for HCV. What is the promise of screening? The promise is that you can treat. Otherwise why screen?”

She acknowledged, however, that the postpartum period is a challenging time for a mother to seek health information or care for herself, whether she’s a new parent or has other children in the home. Nevertheless, the low rate of follow-up and treatment was unexpected. “Even the 70% rate of screening was low – we felt it should have been closer to 100% – but the follow-up rate was surprisingly low,” Dr. Jarlenski said.

Mishka Terplan, MD, MPH, medical director of Friends Research Institute in Baltimore, was not surprised at the low follow-up rate. “The cascade of care for hep C is demoralizing,” said Dr. Terplan, who was not involved in the study. “We know that hep C is syndemic with OUD and other opioid crises and we know that screening is effective for identifying hep C and that antiviral medications are now more effective and less toxic than ever before. But despite this, we’re failing pregnant women and their kids at every step along the cascade. We do a better job with initial testing than with the follow-up testing. We do a horrible job with postpartum medication initiation.”

He pointed to the systemic challenges mothers face in getting postpartum HCV care. “They may be transferred to a subspecialist for treatment, and this transfer is compounded by issues of insurance coverage and eligibility.” With the onus on new mothers to submit the paperwork, “the idea that mothers would be able to initiate much less continue postpartum treatment is absurd,” Dr. Terplan said.

He added that the children born to HCV-positive mothers need surveillance as well, but data suggest that the rates of newborn testing are also low. “There’s a preventable public health burden in all of this.”

The obvious way to increase eradicative therapy would be to treat women while they are getting antenatal care. A small phase 1 trial found that all pregnant participants who were HCV positive and given antivirals in their second trimester were safely treated and gave birth to healthy babies.

“If larger trials prove this treatment is safe and effective, then these results should be communicated to care providers and pregnant patients,” Dr. Jarlenski said. Otherwise, the public health potential of universal screening in pregnancy will not be realized.

This research was supported by the National Institute of Drug Abuse and by the Delaware Division of Medicaid and Medical Assistance and the University of Delaware, Center for Community Research & Service. Dr. Jarlenski disclosed no competing interests. One coauthor disclosed grant funding through her institution from Gilead Sciences and Organon unrelated to this work. Dr. Terplan reported no relevant competing interests.

Children prenatally exposed to opioids alone have an increased risk of attention-deficit/hyperactivity disorder (ADHD), but interactions between opioids and both cannabis use and alcohol use were linked to varying levels of ADHD risk as well, according to findings published March 11 in JAMA Network Open.

While many prenatal exposure studies examine associations with one substance, the results of this case-control study “suggest that it is important to consider prenatal exposure to multiple substances and the interactions between these substances when counseling women regarding substance use during pregnancy,” wrote Henri M. Garrison-Desany of the Johns Hopkins University, Baltimore, and colleagues.

Using data from children in the prospective Boston Birth Cohort between 1998 and 2019, the researchers did a secondary analysis on the 3,138 children (50.4% of whom were male) with at least 2 years of follow-up, excluding children from multiple-gestation pregnancies, in vitro fertilization pregnancies, and deliveries involving major maternal trauma or major chromosomal anomalies. Mothers answered a questionnaire within 24-72 hours of delivery regarding their demographics, substance use, pregnancy history, and health status. Among the mothers, 58.6% were Black, 22.3% were Hispanic, 7.2% were White, 1.5% were Asian, and 10.4% were other races/ethnicities.

The children’s electronic medical records were used to identify those with ADHD diagnoses. The researchers did not assess prescription opioid exposure during pregnancy, but they based opioid exposure on mothers’ reports of recreationally using heroin or oxycodone, mothers’ reports of receiving methadone treatment, or a newborn diagnosis of neonatal abstinence syndrome or neonatal opioid withdrawal syndrome.

Just under a quarter of the women (24.2%) reported using at least one substance during pregnancy. After tobacco smoking (18.5%), the next most reported substances were alcohol (8.1%), cannabis (3.9%), and opioids (1.9%). With a median 12 years of follow-up, 15.5% of the children had been diagnosed with ADHD, most of whom (71.6%) were male.

Before considering interaction of different substances, children exposed to opioids had a little over twice the risk of ADHD (hazard ratio [HR], 2.19) compared to those with no prenatal substance exposure. Although neither cannabis nor alcohol was independently associated with ADHD, smoking had a 40% increased risk, and researchers found a 21% increase in risk of ADHD with each additional substance mothers used during pregnancy. The researchers had adjusted these findings for maternal age, race/ethnicity, marital status, educational level, annual household income, parity, number of perinatal visits, and general stress during pregnancy, based on a structured interview.

When the researchers considered all the substances together, opioid exposure increased risk of ADHD by 60% (HR, 1.6), opioids with cannabis increased risk by 42%, opioids with alcohol increased risk by 15%, and opioids with smoking increased risk by 17%.

”Our findings suggest opioids may interact with other substances (including cannabis), which may be particularly deleterious,” the researchers reported. “It is not clear whether this interaction is owing to biological or environmental factors, such as whether individuals with illicit polysubstance use are more likely to use more substances or whether they have other characteristics that may impact child development.”

The authors noted that cannabis exposure has been linked to other neurodevelopmental outcomes, including reduced executive and motor function in infants. ”Notably, although we did not find a significant independent association between cannabis exposure and ADHD, children exposed to both cannabis and opioids had a 23% greater risk than expected from either exposure individually,” they reported.

The researchers suggest that their findings provide data for considering harm reduction approaches that reduce use of any single substance during pregnancy. “Focusing on the most obviously harmful exposures may be a useful way to reduce the risk of ADHD,” they wrote. “Further work is needed to directly investigate this hypothesis and examine whether reduction in the use of any substance among those with polysubstance use could be acceptable compared with abstinence.”

In an invited commentary, Angela Lupattelli, PhD, and Nhung T. H. Trinh, PhD, both of the department of pharmacy at the University of Oslo, noted the methodological challenges of assessing exposures and associations from multiple different substances during pregnancy.

“First, how can we disentangle the consequences of individual and/or combined substance exposures during pregnancy from the underlying risks?” they asked. In addition to differences in baseline characteristic between those who use opioids or cannabis, Dr. Lupattelli and Dr. Trinh noted that other important unmeasured factors, such as genetics and family environment, may confound the effect size estimates for ADHD.

They also noted the need to consider intensity, dose, duration, and timing of substance use during pregnancy.

“Understanding the longer-term safety of substance use during pregnancy is paramount to inform prevention policy and shape counseling strategies. Observational studies, despite their limitations, are a necessary piece of the puzzle,” they wrote. “However, the study findings should be interpreted with caution, as the use of advanced analytical methods cannot overcome the unavailability of some important confounding factors and exposure information.”

The research was funded by the U.S. Department of Health and Human Services and the National Institutes of Health. The authors had no industry-related disclosures.

Children prenatally exposed to opioids alone have an increased risk of attention-deficit/hyperactivity disorder (ADHD), but interactions between opioids and both cannabis use and alcohol use were linked to varying levels of ADHD risk as well, according to findings published March 11 in JAMA Network Open.

While many prenatal exposure studies examine associations with one substance, the results of this case-control study “suggest that it is important to consider prenatal exposure to multiple substances and the interactions between these substances when counseling women regarding substance use during pregnancy,” wrote Henri M. Garrison-Desany of the Johns Hopkins University, Baltimore, and colleagues.

Using data from children in the prospective Boston Birth Cohort between 1998 and 2019, the researchers did a secondary analysis on the 3,138 children (50.4% of whom were male) with at least 2 years of follow-up, excluding children from multiple-gestation pregnancies, in vitro fertilization pregnancies, and deliveries involving major maternal trauma or major chromosomal anomalies. Mothers answered a questionnaire within 24-72 hours of delivery regarding their demographics, substance use, pregnancy history, and health status. Among the mothers, 58.6% were Black, 22.3% were Hispanic, 7.2% were White, 1.5% were Asian, and 10.4% were other races/ethnicities.

The children’s electronic medical records were used to identify those with ADHD diagnoses. The researchers did not assess prescription opioid exposure during pregnancy, but they based opioid exposure on mothers’ reports of recreationally using heroin or oxycodone, mothers’ reports of receiving methadone treatment, or a newborn diagnosis of neonatal abstinence syndrome or neonatal opioid withdrawal syndrome.

Just under a quarter of the women (24.2%) reported using at least one substance during pregnancy. After tobacco smoking (18.5%), the next most reported substances were alcohol (8.1%), cannabis (3.9%), and opioids (1.9%). With a median 12 years of follow-up, 15.5% of the children had been diagnosed with ADHD, most of whom (71.6%) were male.

Before considering interaction of different substances, children exposed to opioids had a little over twice the risk of ADHD (hazard ratio [HR], 2.19) compared to those with no prenatal substance exposure. Although neither cannabis nor alcohol was independently associated with ADHD, smoking had a 40% increased risk, and researchers found a 21% increase in risk of ADHD with each additional substance mothers used during pregnancy. The researchers had adjusted these findings for maternal age, race/ethnicity, marital status, educational level, annual household income, parity, number of perinatal visits, and general stress during pregnancy, based on a structured interview.

When the researchers considered all the substances together, opioid exposure increased risk of ADHD by 60% (HR, 1.6), opioids with cannabis increased risk by 42%, opioids with alcohol increased risk by 15%, and opioids with smoking increased risk by 17%.

”Our findings suggest opioids may interact with other substances (including cannabis), which may be particularly deleterious,” the researchers reported. “It is not clear whether this interaction is owing to biological or environmental factors, such as whether individuals with illicit polysubstance use are more likely to use more substances or whether they have other characteristics that may impact child development.”

The authors noted that cannabis exposure has been linked to other neurodevelopmental outcomes, including reduced executive and motor function in infants. ”Notably, although we did not find a significant independent association between cannabis exposure and ADHD, children exposed to both cannabis and opioids had a 23% greater risk than expected from either exposure individually,” they reported.

The researchers suggest that their findings provide data for considering harm reduction approaches that reduce use of any single substance during pregnancy. “Focusing on the most obviously harmful exposures may be a useful way to reduce the risk of ADHD,” they wrote. “Further work is needed to directly investigate this hypothesis and examine whether reduction in the use of any substance among those with polysubstance use could be acceptable compared with abstinence.”

In an invited commentary, Angela Lupattelli, PhD, and Nhung T. H. Trinh, PhD, both of the department of pharmacy at the University of Oslo, noted the methodological challenges of assessing exposures and associations from multiple different substances during pregnancy.

“First, how can we disentangle the consequences of individual and/or combined substance exposures during pregnancy from the underlying risks?” they asked. In addition to differences in baseline characteristic between those who use opioids or cannabis, Dr. Lupattelli and Dr. Trinh noted that other important unmeasured factors, such as genetics and family environment, may confound the effect size estimates for ADHD.

They also noted the need to consider intensity, dose, duration, and timing of substance use during pregnancy.

“Understanding the longer-term safety of substance use during pregnancy is paramount to inform prevention policy and shape counseling strategies. Observational studies, despite their limitations, are a necessary piece of the puzzle,” they wrote. “However, the study findings should be interpreted with caution, as the use of advanced analytical methods cannot overcome the unavailability of some important confounding factors and exposure information.”

The research was funded by the U.S. Department of Health and Human Services and the National Institutes of Health. The authors had no industry-related disclosures.

Children prenatally exposed to opioids alone have an increased risk of attention-deficit/hyperactivity disorder (ADHD), but interactions between opioids and both cannabis use and alcohol use were linked to varying levels of ADHD risk as well, according to findings published March 11 in JAMA Network Open.

While many prenatal exposure studies examine associations with one substance, the results of this case-control study “suggest that it is important to consider prenatal exposure to multiple substances and the interactions between these substances when counseling women regarding substance use during pregnancy,” wrote Henri M. Garrison-Desany of the Johns Hopkins University, Baltimore, and colleagues.

Using data from children in the prospective Boston Birth Cohort between 1998 and 2019, the researchers did a secondary analysis on the 3,138 children (50.4% of whom were male) with at least 2 years of follow-up, excluding children from multiple-gestation pregnancies, in vitro fertilization pregnancies, and deliveries involving major maternal trauma or major chromosomal anomalies. Mothers answered a questionnaire within 24-72 hours of delivery regarding their demographics, substance use, pregnancy history, and health status. Among the mothers, 58.6% were Black, 22.3% were Hispanic, 7.2% were White, 1.5% were Asian, and 10.4% were other races/ethnicities.

The children’s electronic medical records were used to identify those with ADHD diagnoses. The researchers did not assess prescription opioid exposure during pregnancy, but they based opioid exposure on mothers’ reports of recreationally using heroin or oxycodone, mothers’ reports of receiving methadone treatment, or a newborn diagnosis of neonatal abstinence syndrome or neonatal opioid withdrawal syndrome.

Just under a quarter of the women (24.2%) reported using at least one substance during pregnancy. After tobacco smoking (18.5%), the next most reported substances were alcohol (8.1%), cannabis (3.9%), and opioids (1.9%). With a median 12 years of follow-up, 15.5% of the children had been diagnosed with ADHD, most of whom (71.6%) were male.

Before considering interaction of different substances, children exposed to opioids had a little over twice the risk of ADHD (hazard ratio [HR], 2.19) compared to those with no prenatal substance exposure. Although neither cannabis nor alcohol was independently associated with ADHD, smoking had a 40% increased risk, and researchers found a 21% increase in risk of ADHD with each additional substance mothers used during pregnancy. The researchers had adjusted these findings for maternal age, race/ethnicity, marital status, educational level, annual household income, parity, number of perinatal visits, and general stress during pregnancy, based on a structured interview.

When the researchers considered all the substances together, opioid exposure increased risk of ADHD by 60% (HR, 1.6), opioids with cannabis increased risk by 42%, opioids with alcohol increased risk by 15%, and opioids with smoking increased risk by 17%.

”Our findings suggest opioids may interact with other substances (including cannabis), which may be particularly deleterious,” the researchers reported. “It is not clear whether this interaction is owing to biological or environmental factors, such as whether individuals with illicit polysubstance use are more likely to use more substances or whether they have other characteristics that may impact child development.”

The authors noted that cannabis exposure has been linked to other neurodevelopmental outcomes, including reduced executive and motor function in infants. ”Notably, although we did not find a significant independent association between cannabis exposure and ADHD, children exposed to both cannabis and opioids had a 23% greater risk than expected from either exposure individually,” they reported.

The researchers suggest that their findings provide data for considering harm reduction approaches that reduce use of any single substance during pregnancy. “Focusing on the most obviously harmful exposures may be a useful way to reduce the risk of ADHD,” they wrote. “Further work is needed to directly investigate this hypothesis and examine whether reduction in the use of any substance among those with polysubstance use could be acceptable compared with abstinence.”

In an invited commentary, Angela Lupattelli, PhD, and Nhung T. H. Trinh, PhD, both of the department of pharmacy at the University of Oslo, noted the methodological challenges of assessing exposures and associations from multiple different substances during pregnancy.

“First, how can we disentangle the consequences of individual and/or combined substance exposures during pregnancy from the underlying risks?” they asked. In addition to differences in baseline characteristic between those who use opioids or cannabis, Dr. Lupattelli and Dr. Trinh noted that other important unmeasured factors, such as genetics and family environment, may confound the effect size estimates for ADHD.

They also noted the need to consider intensity, dose, duration, and timing of substance use during pregnancy.

“Understanding the longer-term safety of substance use during pregnancy is paramount to inform prevention policy and shape counseling strategies. Observational studies, despite their limitations, are a necessary piece of the puzzle,” they wrote. “However, the study findings should be interpreted with caution, as the use of advanced analytical methods cannot overcome the unavailability of some important confounding factors and exposure information.”

The research was funded by the U.S. Department of Health and Human Services and the National Institutes of Health. The authors had no industry-related disclosures.

Pain management is a huge part of how we in palliative care help patients – and most of the time, I think we do it well, but in the regulatory environment of the opioid epidemic, getting opioid prescriptions filled in a timely manner with the clinician’s drug of choice can feel like a Sisyphean task.

A patient – let’s call her Joan – calls me in distress. She is a 62-year-old woman with widespread metastatic breast cancer. Her pain is mainly due to bone metastases, but she also has discomfort due to the cancer’s invasion of the thin membranes that line her lungs and abdomen.

She was started on a combination opioid and acetaminophen tablet about 2 months ago by her oncologist, but is now requiring it around the clock, nearing the ceiling dose for this particular medication.

Given that her pain is escalating, Joan and I discuss starting a long-acting opioid to better manage the peak and trough effect of short-acting opioids, which can make a patient feel that the pain is relieved only for a few hours at a time, with sharp spikes throughout the day that mandate the next dose of short-acting opioid. This tethers the patient to the clock, having to take as many as six or eight doses of medication per day, and can be very disruptive to daily life.

Sarah F. D’Ambruoso, NP, is a palliative care nurse practitioner in Santa Monica, Calif.

Pain management is a huge part of how we in palliative care help patients – and most of the time, I think we do it well, but in the regulatory environment of the opioid epidemic, getting opioid prescriptions filled in a timely manner with the clinician’s drug of choice can feel like a Sisyphean task.

A patient – let’s call her Joan – calls me in distress. She is a 62-year-old woman with widespread metastatic breast cancer. Her pain is mainly due to bone metastases, but she also has discomfort due to the cancer’s invasion of the thin membranes that line her lungs and abdomen.

She was started on a combination opioid and acetaminophen tablet about 2 months ago by her oncologist, but is now requiring it around the clock, nearing the ceiling dose for this particular medication.

Given that her pain is escalating, Joan and I discuss starting a long-acting opioid to better manage the peak and trough effect of short-acting opioids, which can make a patient feel that the pain is relieved only for a few hours at a time, with sharp spikes throughout the day that mandate the next dose of short-acting opioid. This tethers the patient to the clock, having to take as many as six or eight doses of medication per day, and can be very disruptive to daily life.

Sarah F. D’Ambruoso, NP, is a palliative care nurse practitioner in Santa Monica, Calif.

Pain management is a huge part of how we in palliative care help patients – and most of the time, I think we do it well, but in the regulatory environment of the opioid epidemic, getting opioid prescriptions filled in a timely manner with the clinician’s drug of choice can feel like a Sisyphean task.

A patient – let’s call her Joan – calls me in distress. She is a 62-year-old woman with widespread metastatic breast cancer. Her pain is mainly due to bone metastases, but she also has discomfort due to the cancer’s invasion of the thin membranes that line her lungs and abdomen.

She was started on a combination opioid and acetaminophen tablet about 2 months ago by her oncologist, but is now requiring it around the clock, nearing the ceiling dose for this particular medication.

Given that her pain is escalating, Joan and I discuss starting a long-acting opioid to better manage the peak and trough effect of short-acting opioids, which can make a patient feel that the pain is relieved only for a few hours at a time, with sharp spikes throughout the day that mandate the next dose of short-acting opioid. This tethers the patient to the clock, having to take as many as six or eight doses of medication per day, and can be very disruptive to daily life.

Sarah F. D’Ambruoso, NP, is a palliative care nurse practitioner in Santa Monica, Calif.

A new study finding that samples from maternal urine and the meconium of their newborn babies frequently produce different results is raising more questions about drug testing of pregnant women.

The study found concerningly high rates of disagreement (or “discordance”) in biochemical testing between maternal urine in women with a documented history of or active drug use and the meconium in their newborns. In some cases, such discordance might be triggering the inappropriate intervention of childcare protective services, including the separation of infants from their mothers, according to the researchers, who presented their findings Feb. 4 at the meeting sponsored by the Society for Maternal-Fetal Medicine.

“There’s a very big debate right now in the obstetrics and perinatology communities about the utility of biochemical testing and the identification of high-risk women,” lead author Cassandra Heiselman, DO, MPH, clinical assistant professor in the department of obstetrics, gynecology and reproductive medicine at Stony Brook (N.Y.) University, said in an interview. “We know that each biochemical test has limitations, which can include basically the inability to detect all substances, especially synthetic opioids like fentanyl, [and] the possibility for false results.”

Inaccuracies in testing can potentially result in inappropriate separation of mother and baby. “Careful scrutiny of results is needed,” Dr. Heiselman said.

The Stony Brook team conducted a retrospective cohort study that identified women presenting for delivery from January 2017 to March 2021 with indications for drug testing, including a known history of or current substance use disorder/misuse, and late or no prenatal care. A standardized panel was used for testing maternal urine and newborn meconium.

Urine tests of 327 women resulted in 187 (57%) positive and 98 (30%) negative results, along with 42 (13%) samples with incomplete data, the researchers reported. In contrast, drug testing of newborn meconium was positive in 273 (83%) cases, negative in 42 (13%), and was not performed in 12 (4%) – for a rate of concordance of 41%.

Concordance of urine/meconium occurred more frequently in male newborns (65%), compared with females (35%). “It is unclear biologically why there is such a difference based on the sex of the infants’ test and is an area that needs further investigation,” Dr. Heiselman said.

Comparing urine and meconium tests for 11 substances resulted in 195/483 (40%) concordance, the researchers said; 18% were discordant with positive maternal urine, and 41% were discordant with newborn positive meconium.

Oxycodone and fentanyl were significantly discordant with positive maternal urine. Cannabis use was the most common factor associated with a positive test of meconium, according to the researchers.

“Some studies have shown cannabis use in the second trimester can show up in meconium testing even if the mother has stopped that behavior,” Dr. Heiselman said. “Then there is also cross-reactivity with other substances that can lead to higher false positive results, especially in the urine toxicology.”

The reasons for the discordant results are not clear and vary by substance, Dr. Heiselman said.

“Cannabis and methadone were the significant factors leading to discordance with positive newborn meconium, which may reflect prior use earlier in pregnancy without recent use before delivery,” she said in an interview. “Urine and meconium reflect potentially different timing in perinatal exposure and the potential differences in windows of detection for different substances. Therefore, we would expect some discordance in our comparisons, just not the extent that we saw.”

Some test results might also have been false positives. Many commonly used medications, from cough syrups to proton pump inhibitors, have the potential to generate positive results for illicit drugs, Dr. Heiselman said.

“The issue of discordance is a complex one, where there are limitations of the tests being performed, possible cross-reactivity with false positives, and the difference in what test reflects as far as timing of prenatal exposure. Furthermore, a negative test does not rule out sporadic use, nor does a positive result diagnose substance use disorder or its severity,” she said.
 

Lack of standards

Dr. Heiselman said states and the federal government lack standards to biochemically evaluate women at risk for drug abuse and their newborns.

“My institution uses a risk-based protocol. Basically, we test cases where we have a known history of substance use disorder or active use, a history in the last 3 years of any kind of substance use, initiation of late prenatal care after 20 weeks, or no prenatal care at all,” she said. “And then the pediatricians on the other side will test neonates if the mother has any of that history or if the neonates themselves have unexplained complications or drug withdrawal symptoms.”

High rates of discordance can result in the inappropriate intervention by childcare protective service agencies when the mother may not have a substance use disorder, she noted.

Perinatologist Kecia Gaither, MD, MPH, associate professor of clinical obstetrics and gynecology at Weill Cornell Medicine, New York, called the findings “no surprise,” but added that negative findings in neonates “do not exclude the possibility of substance abuse by the mother. It is important to recognize the limitations inherent with screening tests for illicit substances in neonates from substance-abusing mothers.”

Dr. Heiselman added that understanding what maternal and infant drug tests truly reflect “can help us as clinicians in deciding when we test, whether it’s medically necessary, instead of just thinking biochemical tests are the best screening tool, because we know that we are screening. We must engage these women in empathetic and nonjudgmental discussions, which often will elucidate a substance use disorder history more so than just biochemical testing, negative or positive.”

The researchers disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A new study finding that samples from maternal urine and the meconium of their newborn babies frequently produce different results is raising more questions about drug testing of pregnant women.

The study found concerningly high rates of disagreement (or “discordance”) in biochemical testing between maternal urine in women with a documented history of or active drug use and the meconium in their newborns. In some cases, such discordance might be triggering the inappropriate intervention of childcare protective services, including the separation of infants from their mothers, according to the researchers, who presented their findings Feb. 4 at the meeting sponsored by the Society for Maternal-Fetal Medicine.

“There’s a very big debate right now in the obstetrics and perinatology communities about the utility of biochemical testing and the identification of high-risk women,” lead author Cassandra Heiselman, DO, MPH, clinical assistant professor in the department of obstetrics, gynecology and reproductive medicine at Stony Brook (N.Y.) University, said in an interview. “We know that each biochemical test has limitations, which can include basically the inability to detect all substances, especially synthetic opioids like fentanyl, [and] the possibility for false results.”

Inaccuracies in testing can potentially result in inappropriate separation of mother and baby. “Careful scrutiny of results is needed,” Dr. Heiselman said.

The Stony Brook team conducted a retrospective cohort study that identified women presenting for delivery from January 2017 to March 2021 with indications for drug testing, including a known history of or current substance use disorder/misuse, and late or no prenatal care. A standardized panel was used for testing maternal urine and newborn meconium.

Urine tests of 327 women resulted in 187 (57%) positive and 98 (30%) negative results, along with 42 (13%) samples with incomplete data, the researchers reported. In contrast, drug testing of newborn meconium was positive in 273 (83%) cases, negative in 42 (13%), and was not performed in 12 (4%) – for a rate of concordance of 41%.

Concordance of urine/meconium occurred more frequently in male newborns (65%), compared with females (35%). “It is unclear biologically why there is such a difference based on the sex of the infants’ test and is an area that needs further investigation,” Dr. Heiselman said.

Comparing urine and meconium tests for 11 substances resulted in 195/483 (40%) concordance, the researchers said; 18% were discordant with positive maternal urine, and 41% were discordant with newborn positive meconium.

Oxycodone and fentanyl were significantly discordant with positive maternal urine. Cannabis use was the most common factor associated with a positive test of meconium, according to the researchers.

“Some studies have shown cannabis use in the second trimester can show up in meconium testing even if the mother has stopped that behavior,” Dr. Heiselman said. “Then there is also cross-reactivity with other substances that can lead to higher false positive results, especially in the urine toxicology.”

The reasons for the discordant results are not clear and vary by substance, Dr. Heiselman said.

“Cannabis and methadone were the significant factors leading to discordance with positive newborn meconium, which may reflect prior use earlier in pregnancy without recent use before delivery,” she said in an interview. “Urine and meconium reflect potentially different timing in perinatal exposure and the potential differences in windows of detection for different substances. Therefore, we would expect some discordance in our comparisons, just not the extent that we saw.”

Some test results might also have been false positives. Many commonly used medications, from cough syrups to proton pump inhibitors, have the potential to generate positive results for illicit drugs, Dr. Heiselman said.

“The issue of discordance is a complex one, where there are limitations of the tests being performed, possible cross-reactivity with false positives, and the difference in what test reflects as far as timing of prenatal exposure. Furthermore, a negative test does not rule out sporadic use, nor does a positive result diagnose substance use disorder or its severity,” she said.
 

Lack of standards

Dr. Heiselman said states and the federal government lack standards to biochemically evaluate women at risk for drug abuse and their newborns.

“My institution uses a risk-based protocol. Basically, we test cases where we have a known history of substance use disorder or active use, a history in the last 3 years of any kind of substance use, initiation of late prenatal care after 20 weeks, or no prenatal care at all,” she said. “And then the pediatricians on the other side will test neonates if the mother has any of that history or if the neonates themselves have unexplained complications or drug withdrawal symptoms.”

High rates of discordance can result in the inappropriate intervention by childcare protective service agencies when the mother may not have a substance use disorder, she noted.

Perinatologist Kecia Gaither, MD, MPH, associate professor of clinical obstetrics and gynecology at Weill Cornell Medicine, New York, called the findings “no surprise,” but added that negative findings in neonates “do not exclude the possibility of substance abuse by the mother. It is important to recognize the limitations inherent with screening tests for illicit substances in neonates from substance-abusing mothers.”

Dr. Heiselman added that understanding what maternal and infant drug tests truly reflect “can help us as clinicians in deciding when we test, whether it’s medically necessary, instead of just thinking biochemical tests are the best screening tool, because we know that we are screening. We must engage these women in empathetic and nonjudgmental discussions, which often will elucidate a substance use disorder history more so than just biochemical testing, negative or positive.”

The researchers disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A new study finding that samples from maternal urine and the meconium of their newborn babies frequently produce different results is raising more questions about drug testing of pregnant women.

The study found concerningly high rates of disagreement (or “discordance”) in biochemical testing between maternal urine in women with a documented history of or active drug use and the meconium in their newborns. In some cases, such discordance might be triggering the inappropriate intervention of childcare protective services, including the separation of infants from their mothers, according to the researchers, who presented their findings Feb. 4 at the meeting sponsored by the Society for Maternal-Fetal Medicine.

“There’s a very big debate right now in the obstetrics and perinatology communities about the utility of biochemical testing and the identification of high-risk women,” lead author Cassandra Heiselman, DO, MPH, clinical assistant professor in the department of obstetrics, gynecology and reproductive medicine at Stony Brook (N.Y.) University, said in an interview. “We know that each biochemical test has limitations, which can include basically the inability to detect all substances, especially synthetic opioids like fentanyl, [and] the possibility for false results.”

Inaccuracies in testing can potentially result in inappropriate separation of mother and baby. “Careful scrutiny of results is needed,” Dr. Heiselman said.

The Stony Brook team conducted a retrospective cohort study that identified women presenting for delivery from January 2017 to March 2021 with indications for drug testing, including a known history of or current substance use disorder/misuse, and late or no prenatal care. A standardized panel was used for testing maternal urine and newborn meconium.

Urine tests of 327 women resulted in 187 (57%) positive and 98 (30%) negative results, along with 42 (13%) samples with incomplete data, the researchers reported. In contrast, drug testing of newborn meconium was positive in 273 (83%) cases, negative in 42 (13%), and was not performed in 12 (4%) – for a rate of concordance of 41%.

Concordance of urine/meconium occurred more frequently in male newborns (65%), compared with females (35%). “It is unclear biologically why there is such a difference based on the sex of the infants’ test and is an area that needs further investigation,” Dr. Heiselman said.

Comparing urine and meconium tests for 11 substances resulted in 195/483 (40%) concordance, the researchers said; 18% were discordant with positive maternal urine, and 41% were discordant with newborn positive meconium.

Oxycodone and fentanyl were significantly discordant with positive maternal urine. Cannabis use was the most common factor associated with a positive test of meconium, according to the researchers.

“Some studies have shown cannabis use in the second trimester can show up in meconium testing even if the mother has stopped that behavior,” Dr. Heiselman said. “Then there is also cross-reactivity with other substances that can lead to higher false positive results, especially in the urine toxicology.”

The reasons for the discordant results are not clear and vary by substance, Dr. Heiselman said.

“Cannabis and methadone were the significant factors leading to discordance with positive newborn meconium, which may reflect prior use earlier in pregnancy without recent use before delivery,” she said in an interview. “Urine and meconium reflect potentially different timing in perinatal exposure and the potential differences in windows of detection for different substances. Therefore, we would expect some discordance in our comparisons, just not the extent that we saw.”

Some test results might also have been false positives. Many commonly used medications, from cough syrups to proton pump inhibitors, have the potential to generate positive results for illicit drugs, Dr. Heiselman said.

“The issue of discordance is a complex one, where there are limitations of the tests being performed, possible cross-reactivity with false positives, and the difference in what test reflects as far as timing of prenatal exposure. Furthermore, a negative test does not rule out sporadic use, nor does a positive result diagnose substance use disorder or its severity,” she said.
 

Lack of standards

Dr. Heiselman said states and the federal government lack standards to biochemically evaluate women at risk for drug abuse and their newborns.

“My institution uses a risk-based protocol. Basically, we test cases where we have a known history of substance use disorder or active use, a history in the last 3 years of any kind of substance use, initiation of late prenatal care after 20 weeks, or no prenatal care at all,” she said. “And then the pediatricians on the other side will test neonates if the mother has any of that history or if the neonates themselves have unexplained complications or drug withdrawal symptoms.”

High rates of discordance can result in the inappropriate intervention by childcare protective service agencies when the mother may not have a substance use disorder, she noted.

Perinatologist Kecia Gaither, MD, MPH, associate professor of clinical obstetrics and gynecology at Weill Cornell Medicine, New York, called the findings “no surprise,” but added that negative findings in neonates “do not exclude the possibility of substance abuse by the mother. It is important to recognize the limitations inherent with screening tests for illicit substances in neonates from substance-abusing mothers.”

Dr. Heiselman added that understanding what maternal and infant drug tests truly reflect “can help us as clinicians in deciding when we test, whether it’s medically necessary, instead of just thinking biochemical tests are the best screening tool, because we know that we are screening. We must engage these women in empathetic and nonjudgmental discussions, which often will elucidate a substance use disorder history more so than just biochemical testing, negative or positive.”

The researchers disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Exposure to opioid analgesics during the first trimester of pregnancy appears to increase the risk of congenital anomalies diagnosed in the first year of life, researchers report.

While the absolute risk of congenital anomalies was low, these findings add to an increasing body of evidence suggesting that prenatal exposure to opioids may confer harm to infants post partum.

“We undertook a population-based cohort study to estimate associations between opioid analgesic exposure during the first trimester and congenital anomalies using health administrative data capturing all narcotic prescriptions during pregnancy,” lead author Alexa C. Bowie, MPH, of Queen’s University in Kingston, Ont., and colleagues reported in CMAJ.

The researchers retrospectively reviewed administrative health data in a single-payer health care system from 2013 to 2018. They identified parent-infant pair records for all live births and stillbirths that occurred at more than 20 weeks’ gestation.

The exposure of interest was a prescription for any opioid analgesic with a fill date between the estimated date of conception and less than 14 weeks’ gestation. The referent group included any infant not exposed to an opioid analgesic during the index pregnancy period.
 

Results

The study cohort included a total of 599,579 gestational parent-infant pairs. Of these, 11,903 (2.0%) were exposed to opioid analgesics, and most were exposed during the first trimester only (75.8%).

Overall, 2.0% of these infants developed a congenital anomaly during the first year of life; the prevalence of congenital anomalies was 2.0% in unexposed infants and 2.8% in exposed infants.

Relative to unexposed infants, the researchers observed greater risks among infants who were exposed for some anomaly groups, including many specific anomalies, such as ankyloglossia (any opioid: adjusted risk ratio, 1.88; 95% confidence interval, 1.30-2.72; codeine: aRR, 2.14; 95% CI, 1.35-3.40), as well as gastrointestinal anomalies (any opioid: aRR, 1.46; 95% CI, 1.15-1.85; codeine: aRR, 1.53; 95% CI, 1.12-2.09; tramadol: aRR, 2.69; 95% CI 1.34-5.38).

After sensitivity analyses, which included exposure 4 weeks before conception or excluded individuals with exposure to opioid analgesics before pregnancy, the findings remained unchanged.

“Although the overall risk was low, we observed an increased risk of any congenital anomaly with tramadol, and a previously unreported risk with morphine,” the researchers wrote.

“Previous studies reported elevated risks of heart anomalies with first-trimester exposure to any opioid analgesic, codeine, and tramadol, but others reported no association with any opioid analgesic or codeine,” they explained.
 

Interpreting the results

Study author Susan Brogly, PhD, of Queen’s University said “Our population-based study confirms evidence of a small increased risk of birth defects from opioid analgesic exposure in the first trimester that was observed in a recent study of private insurance and Medicaid beneficiaries in the U.S. We further show that this small increased risk is not due to other risk factors for fetal harm in women who may take these medications.”

“An opioid prescription dispensed in the first trimester would imply that there was an acute injury or chronic condition also present in the first trimester, which may also be associated with congenital abnormalities,” commented Elisabeth Poorman, MD, MPH, a clinical instructor and primary care physician at the University of Washington in Seattle.

“Opioid use disorder is often diagnosed incorrectly; since the researchers used diagnostic billing codes to exclude individuals with opioid use disorder, some women may have been missed,” Dr. Poorman explained.

Ms. Bowie and colleagues acknowledged that a key limitation of the study was the identification of cases using diagnostic billing codes. As a result, exposure-dependent recording bias could be present and limit the applicability of the findings.

“The diagnosis and documentation of minor anomalies and those with subtle medical significance could be vulnerable to exposure-dependent recording bias,” Ms. Bowie wrote.

Dr. Poorman recommended that these results should be interpreted with caution given these and other limitations. “Overall, results from this study may imply that there is limited evidence to suspect opioids are related to congenital abnormalities due to a very small difference observed in relatively unequal groups,” she concluded.

This study received funding from the Eunice Kennedy Shriver National Institutes of Child Health and Human Development and was also supported by the Institute for Clinical Evaluative Sciences, which is funded by an annual grant from the Ontario Ministry of Health. One author reported receiving honoraria from the National Institutes of Health and a grant from the Canadian Institute of Health Research, outside the submitted work. No other competing interests were declared.

Exposure to opioid analgesics during the first trimester of pregnancy appears to increase the risk of congenital anomalies diagnosed in the first year of life, researchers report.

While the absolute risk of congenital anomalies was low, these findings add to an increasing body of evidence suggesting that prenatal exposure to opioids may confer harm to infants post partum.

“We undertook a population-based cohort study to estimate associations between opioid analgesic exposure during the first trimester and congenital anomalies using health administrative data capturing all narcotic prescriptions during pregnancy,” lead author Alexa C. Bowie, MPH, of Queen’s University in Kingston, Ont., and colleagues reported in CMAJ.

The researchers retrospectively reviewed administrative health data in a single-payer health care system from 2013 to 2018. They identified parent-infant pair records for all live births and stillbirths that occurred at more than 20 weeks’ gestation.

The exposure of interest was a prescription for any opioid analgesic with a fill date between the estimated date of conception and less than 14 weeks’ gestation. The referent group included any infant not exposed to an opioid analgesic during the index pregnancy period.
 

Results

The study cohort included a total of 599,579 gestational parent-infant pairs. Of these, 11,903 (2.0%) were exposed to opioid analgesics, and most were exposed during the first trimester only (75.8%).

Overall, 2.0% of these infants developed a congenital anomaly during the first year of life; the prevalence of congenital anomalies was 2.0% in unexposed infants and 2.8% in exposed infants.

Relative to unexposed infants, the researchers observed greater risks among infants who were exposed for some anomaly groups, including many specific anomalies, such as ankyloglossia (any opioid: adjusted risk ratio, 1.88; 95% confidence interval, 1.30-2.72; codeine: aRR, 2.14; 95% CI, 1.35-3.40), as well as gastrointestinal anomalies (any opioid: aRR, 1.46; 95% CI, 1.15-1.85; codeine: aRR, 1.53; 95% CI, 1.12-2.09; tramadol: aRR, 2.69; 95% CI 1.34-5.38).

After sensitivity analyses, which included exposure 4 weeks before conception or excluded individuals with exposure to opioid analgesics before pregnancy, the findings remained unchanged.

“Although the overall risk was low, we observed an increased risk of any congenital anomaly with tramadol, and a previously unreported risk with morphine,” the researchers wrote.

“Previous studies reported elevated risks of heart anomalies with first-trimester exposure to any opioid analgesic, codeine, and tramadol, but others reported no association with any opioid analgesic or codeine,” they explained.
 

Interpreting the results

Study author Susan Brogly, PhD, of Queen’s University said “Our population-based study confirms evidence of a small increased risk of birth defects from opioid analgesic exposure in the first trimester that was observed in a recent study of private insurance and Medicaid beneficiaries in the U.S. We further show that this small increased risk is not due to other risk factors for fetal harm in women who may take these medications.”

“An opioid prescription dispensed in the first trimester would imply that there was an acute injury or chronic condition also present in the first trimester, which may also be associated with congenital abnormalities,” commented Elisabeth Poorman, MD, MPH, a clinical instructor and primary care physician at the University of Washington in Seattle.

“Opioid use disorder is often diagnosed incorrectly; since the researchers used diagnostic billing codes to exclude individuals with opioid use disorder, some women may have been missed,” Dr. Poorman explained.

Ms. Bowie and colleagues acknowledged that a key limitation of the study was the identification of cases using diagnostic billing codes. As a result, exposure-dependent recording bias could be present and limit the applicability of the findings.

“The diagnosis and documentation of minor anomalies and those with subtle medical significance could be vulnerable to exposure-dependent recording bias,” Ms. Bowie wrote.

Dr. Poorman recommended that these results should be interpreted with caution given these and other limitations. “Overall, results from this study may imply that there is limited evidence to suspect opioids are related to congenital abnormalities due to a very small difference observed in relatively unequal groups,” she concluded.

This study received funding from the Eunice Kennedy Shriver National Institutes of Child Health and Human Development and was also supported by the Institute for Clinical Evaluative Sciences, which is funded by an annual grant from the Ontario Ministry of Health. One author reported receiving honoraria from the National Institutes of Health and a grant from the Canadian Institute of Health Research, outside the submitted work. No other competing interests were declared.

Exposure to opioid analgesics during the first trimester of pregnancy appears to increase the risk of congenital anomalies diagnosed in the first year of life, researchers report.

While the absolute risk of congenital anomalies was low, these findings add to an increasing body of evidence suggesting that prenatal exposure to opioids may confer harm to infants post partum.

“We undertook a population-based cohort study to estimate associations between opioid analgesic exposure during the first trimester and congenital anomalies using health administrative data capturing all narcotic prescriptions during pregnancy,” lead author Alexa C. Bowie, MPH, of Queen’s University in Kingston, Ont., and colleagues reported in CMAJ.

The researchers retrospectively reviewed administrative health data in a single-payer health care system from 2013 to 2018. They identified parent-infant pair records for all live births and stillbirths that occurred at more than 20 weeks’ gestation.

The exposure of interest was a prescription for any opioid analgesic with a fill date between the estimated date of conception and less than 14 weeks’ gestation. The referent group included any infant not exposed to an opioid analgesic during the index pregnancy period.
 

Results

The study cohort included a total of 599,579 gestational parent-infant pairs. Of these, 11,903 (2.0%) were exposed to opioid analgesics, and most were exposed during the first trimester only (75.8%).

Overall, 2.0% of these infants developed a congenital anomaly during the first year of life; the prevalence of congenital anomalies was 2.0% in unexposed infants and 2.8% in exposed infants.

Relative to unexposed infants, the researchers observed greater risks among infants who were exposed for some anomaly groups, including many specific anomalies, such as ankyloglossia (any opioid: adjusted risk ratio, 1.88; 95% confidence interval, 1.30-2.72; codeine: aRR, 2.14; 95% CI, 1.35-3.40), as well as gastrointestinal anomalies (any opioid: aRR, 1.46; 95% CI, 1.15-1.85; codeine: aRR, 1.53; 95% CI, 1.12-2.09; tramadol: aRR, 2.69; 95% CI 1.34-5.38).

After sensitivity analyses, which included exposure 4 weeks before conception or excluded individuals with exposure to opioid analgesics before pregnancy, the findings remained unchanged.

“Although the overall risk was low, we observed an increased risk of any congenital anomaly with tramadol, and a previously unreported risk with morphine,” the researchers wrote.

“Previous studies reported elevated risks of heart anomalies with first-trimester exposure to any opioid analgesic, codeine, and tramadol, but others reported no association with any opioid analgesic or codeine,” they explained.
 

Interpreting the results

Study author Susan Brogly, PhD, of Queen’s University said “Our population-based study confirms evidence of a small increased risk of birth defects from opioid analgesic exposure in the first trimester that was observed in a recent study of private insurance and Medicaid beneficiaries in the U.S. We further show that this small increased risk is not due to other risk factors for fetal harm in women who may take these medications.”

“An opioid prescription dispensed in the first trimester would imply that there was an acute injury or chronic condition also present in the first trimester, which may also be associated with congenital abnormalities,” commented Elisabeth Poorman, MD, MPH, a clinical instructor and primary care physician at the University of Washington in Seattle.

“Opioid use disorder is often diagnosed incorrectly; since the researchers used diagnostic billing codes to exclude individuals with opioid use disorder, some women may have been missed,” Dr. Poorman explained.

Ms. Bowie and colleagues acknowledged that a key limitation of the study was the identification of cases using diagnostic billing codes. As a result, exposure-dependent recording bias could be present and limit the applicability of the findings.

“The diagnosis and documentation of minor anomalies and those with subtle medical significance could be vulnerable to exposure-dependent recording bias,” Ms. Bowie wrote.

Dr. Poorman recommended that these results should be interpreted with caution given these and other limitations. “Overall, results from this study may imply that there is limited evidence to suspect opioids are related to congenital abnormalities due to a very small difference observed in relatively unequal groups,” she concluded.

This study received funding from the Eunice Kennedy Shriver National Institutes of Child Health and Human Development and was also supported by the Institute for Clinical Evaluative Sciences, which is funded by an annual grant from the Ontario Ministry of Health. One author reported receiving honoraria from the National Institutes of Health and a grant from the Canadian Institute of Health Research, outside the submitted work. No other competing interests were declared.

Two illicit drugs are contributing to a sharp rise in fentanyl-related deaths, a new study from the Centers for Disease Control and Prevention shows.

Para-fluorofentanyl, a schedule I substance often found in heroin packets and counterfeit pills, is making a comeback on the illicit drug market, Jordan Trecki, PhD, and associates reported in the Centers for Disease Control and Prevention’s Morbidity and Mortality Weekly Report (2022 Jan 28;71[4]:153-5). U.S. medical examiner reports and national law enforcement seizure data point to a rise in encounters of this drug along with metonitazene, a benzimidazole-opioid, in combination with fentanyl.

On their own, para-fluorofentanyl and metonitazene can kill the user through respiratory depression. Combinations of these substances and other opioids, including fentanyl-related compounds or adulterants, “pose an even greater potential harm to the patient than previously observed,” reported Dr. Trecki, a pharmacologist affiliated with the Drug Enforcement Administration, and colleagues.

Opioids contribute to about 75% of all U.S. drug overdose deaths, which rose by 28.5% during 2020-2021, according to the National Center for Health Statistics. And fentanyl is replacing heroin as the primary drug of use, said addiction specialist Brian Fuehrlein, MD, PhD, in an interview.

“For patients with stimulant use disorder and even cannabis use disorder, fentanyl is becoming more and more common as an adulterant in those substances, often resulting in inadvertent use. Hence, fentanyl and fentanyl-like drugs and fentanyl analogues are becoming increasingly common and important,” said Dr. Fuehrlein, director of the psychiatric emergency room at the VA Connecticut Healthcare System. He was not involved with the MMWR study.
 

Tennessee data reflect national problem

Recent data from a medical examiner in Knoxville, Tenn., illustrate what might be happening nationwide with those two emerging substances.

Over the last 2 years, the Knox County Regional Forensic Center has identified para-fluorofentanyl in the toxicology results of drug overdose victims, and metonitazene – either on its own or in combination with fentanyl and para-fluorofentanyl. Fentanyl appeared in 562 or 73% of 770 unintentional drug overdose deaths from November 2020 to August 2021. Forty-eight of these cases involved para-fluorofentanyl, and 26 involved metonitazene.

“Although the percentage of law enforcement encounters with these substances in Tennessee decreased relative to the national total percentage within this time frame, the increase in encounters both within Tennessee and nationally reflect an increased distribution of para-fluorofentanyl and metonitazene throughout the United States,” the authors reported.
 

How to identify substances, manage overdoses

The authors encouraged physicians, labs, and medical examiners to be on the lookout for these two substances either in the emergency department or when identifying the cause of drug overdose deaths.

They also advised that stronger opioids, such as fentanyl, para-fluorofentanyl, metonitazene, or other benzimidazoles may warrant additional doses of the opioid-reversal drug naloxone.

While he hasn’t personally seen any of these drugs in his practice, “I would assume that these are on the rise due to inexpensive cost to manufacture and potency of effect,” said Dr. Fuehrlein, also an associate professor of psychiatry at Yale University, New Haven, Conn.

The need for additional naloxone to manage acute overdoses is a key takeaway of the MMWR paper, he added. Clinicians should also educate patients about harm reduction strategies to avoid overdose death when using potentially powerful and unknown drugs. “Things like start low and go slow, buy from the same supplier, do not use opioids with alcohol or benzos, have Narcan available, do not use alone, etc.”

Dr. Fuehrlein had no disclosures.

Two illicit drugs are contributing to a sharp rise in fentanyl-related deaths, a new study from the Centers for Disease Control and Prevention shows.

Para-fluorofentanyl, a schedule I substance often found in heroin packets and counterfeit pills, is making a comeback on the illicit drug market, Jordan Trecki, PhD, and associates reported in the Centers for Disease Control and Prevention’s Morbidity and Mortality Weekly Report (2022 Jan 28;71[4]:153-5). U.S. medical examiner reports and national law enforcement seizure data point to a rise in encounters of this drug along with metonitazene, a benzimidazole-opioid, in combination with fentanyl.

On their own, para-fluorofentanyl and metonitazene can kill the user through respiratory depression. Combinations of these substances and other opioids, including fentanyl-related compounds or adulterants, “pose an even greater potential harm to the patient than previously observed,” reported Dr. Trecki, a pharmacologist affiliated with the Drug Enforcement Administration, and colleagues.

Opioids contribute to about 75% of all U.S. drug overdose deaths, which rose by 28.5% during 2020-2021, according to the National Center for Health Statistics. And fentanyl is replacing heroin as the primary drug of use, said addiction specialist Brian Fuehrlein, MD, PhD, in an interview.

“For patients with stimulant use disorder and even cannabis use disorder, fentanyl is becoming more and more common as an adulterant in those substances, often resulting in inadvertent use. Hence, fentanyl and fentanyl-like drugs and fentanyl analogues are becoming increasingly common and important,” said Dr. Fuehrlein, director of the psychiatric emergency room at the VA Connecticut Healthcare System. He was not involved with the MMWR study.
 

Tennessee data reflect national problem

Recent data from a medical examiner in Knoxville, Tenn., illustrate what might be happening nationwide with those two emerging substances.

Over the last 2 years, the Knox County Regional Forensic Center has identified para-fluorofentanyl in the toxicology results of drug overdose victims, and metonitazene – either on its own or in combination with fentanyl and para-fluorofentanyl. Fentanyl appeared in 562 or 73% of 770 unintentional drug overdose deaths from November 2020 to August 2021. Forty-eight of these cases involved para-fluorofentanyl, and 26 involved metonitazene.

“Although the percentage of law enforcement encounters with these substances in Tennessee decreased relative to the national total percentage within this time frame, the increase in encounters both within Tennessee and nationally reflect an increased distribution of para-fluorofentanyl and metonitazene throughout the United States,” the authors reported.
 

How to identify substances, manage overdoses

The authors encouraged physicians, labs, and medical examiners to be on the lookout for these two substances either in the emergency department or when identifying the cause of drug overdose deaths.

They also advised that stronger opioids, such as fentanyl, para-fluorofentanyl, metonitazene, or other benzimidazoles may warrant additional doses of the opioid-reversal drug naloxone.

While he hasn’t personally seen any of these drugs in his practice, “I would assume that these are on the rise due to inexpensive cost to manufacture and potency of effect,” said Dr. Fuehrlein, also an associate professor of psychiatry at Yale University, New Haven, Conn.

The need for additional naloxone to manage acute overdoses is a key takeaway of the MMWR paper, he added. Clinicians should also educate patients about harm reduction strategies to avoid overdose death when using potentially powerful and unknown drugs. “Things like start low and go slow, buy from the same supplier, do not use opioids with alcohol or benzos, have Narcan available, do not use alone, etc.”

Dr. Fuehrlein had no disclosures.

Two illicit drugs are contributing to a sharp rise in fentanyl-related deaths, a new study from the Centers for Disease Control and Prevention shows.

Para-fluorofentanyl, a schedule I substance often found in heroin packets and counterfeit pills, is making a comeback on the illicit drug market, Jordan Trecki, PhD, and associates reported in the Centers for Disease Control and Prevention’s Morbidity and Mortality Weekly Report (2022 Jan 28;71[4]:153-5). U.S. medical examiner reports and national law enforcement seizure data point to a rise in encounters of this drug along with metonitazene, a benzimidazole-opioid, in combination with fentanyl.

On their own, para-fluorofentanyl and metonitazene can kill the user through respiratory depression. Combinations of these substances and other opioids, including fentanyl-related compounds or adulterants, “pose an even greater potential harm to the patient than previously observed,” reported Dr. Trecki, a pharmacologist affiliated with the Drug Enforcement Administration, and colleagues.

Opioids contribute to about 75% of all U.S. drug overdose deaths, which rose by 28.5% during 2020-2021, according to the National Center for Health Statistics. And fentanyl is replacing heroin as the primary drug of use, said addiction specialist Brian Fuehrlein, MD, PhD, in an interview.

“For patients with stimulant use disorder and even cannabis use disorder, fentanyl is becoming more and more common as an adulterant in those substances, often resulting in inadvertent use. Hence, fentanyl and fentanyl-like drugs and fentanyl analogues are becoming increasingly common and important,” said Dr. Fuehrlein, director of the psychiatric emergency room at the VA Connecticut Healthcare System. He was not involved with the MMWR study.
 

Tennessee data reflect national problem

Recent data from a medical examiner in Knoxville, Tenn., illustrate what might be happening nationwide with those two emerging substances.

Over the last 2 years, the Knox County Regional Forensic Center has identified para-fluorofentanyl in the toxicology results of drug overdose victims, and metonitazene – either on its own or in combination with fentanyl and para-fluorofentanyl. Fentanyl appeared in 562 or 73% of 770 unintentional drug overdose deaths from November 2020 to August 2021. Forty-eight of these cases involved para-fluorofentanyl, and 26 involved metonitazene.

“Although the percentage of law enforcement encounters with these substances in Tennessee decreased relative to the national total percentage within this time frame, the increase in encounters both within Tennessee and nationally reflect an increased distribution of para-fluorofentanyl and metonitazene throughout the United States,” the authors reported.
 

How to identify substances, manage overdoses

The authors encouraged physicians, labs, and medical examiners to be on the lookout for these two substances either in the emergency department or when identifying the cause of drug overdose deaths.

They also advised that stronger opioids, such as fentanyl, para-fluorofentanyl, metonitazene, or other benzimidazoles may warrant additional doses of the opioid-reversal drug naloxone.

While he hasn’t personally seen any of these drugs in his practice, “I would assume that these are on the rise due to inexpensive cost to manufacture and potency of effect,” said Dr. Fuehrlein, also an associate professor of psychiatry at Yale University, New Haven, Conn.

The need for additional naloxone to manage acute overdoses is a key takeaway of the MMWR paper, he added. Clinicians should also educate patients about harm reduction strategies to avoid overdose death when using potentially powerful and unknown drugs. “Things like start low and go slow, buy from the same supplier, do not use opioids with alcohol or benzos, have Narcan available, do not use alone, etc.”

Dr. Fuehrlein had no disclosures.