Opinion

Mood instability, or sudden, unpredictable, and frequent shifts in emotional states, characterizes many types of psychiatric disorder, including attention-deficit/hyperactivity disorder (ADHD), personality disorders, depression, and posttraumatic stress disorder. To say that individuals with bipolar disorder (BD) have mood instability sounds like a tautology. Nonetheless, mood instability has particular relevance to BD: Many patients have irregular or labile moods even when they are between major episodes of mania and depression.¹

Children of parents with BD who have high levels of mood instability are at particularly high risk for developing BD (types I or II) in late adolescence or early adulthood.² The following case provides an illustration:

Patrick, age 14, entered treatment with diagnoses of ADHD and other specified bipolar disorder. His mother felt that his behavior resembled that of his father, who had been treated for manic episodes. During the COVID-19 pandemic, Patrick had become increasingly difficult at home, with significant oppositionality, impulsive behavior, and difficulty following through on school assignments or household tasks. His mother’s most significant complaints concerned Patrick’s sudden outbursts of anger and abrupt verbal abuse when she asked him to stop playing video games. When interrupted, he cursed loudly and sometimes turned violent; he had broken a window and a door at home and had on one occasion physically attacked his younger brother. Patrick agreed that he became angry at times, but felt that others provoked him. When queried about depression, he described anxiety and worry. He was unable to describe a particular trigger for his anxiety except for being interrupted in online games with his friends, which made him “feel like a total loser.”

His mother reported that Patrick had multiple 1- to 2-day intervals in which he became “really silly, laughing at nothing,” talking rapidly, jumping from one topic to another, and becoming annoyed when others didn’t share his enthusiasm. In these activated intervals, he slept little and seemed to be full of energy; his mother would hear him talking loudly into his phone throughout the night. During one such interval he had become verbally aggressive with a peer, which had ruined their friendship. Both Patrick and his mother reported that they had been fighting constantly and, in her words, “our house has become a war zone.”

In our recent article in the Journal of the American Academy of Child and Adolescent Psychiatry,³ my coauthors and I examined the association between parents’ ratings of mood instability and clinicians’ longitudinal ratings of symptoms and functioning among youth (ages 9-17 years) who were at high risk for BD. The participants met DSM-5 diagnostic criteria for major depressive disorder or other specified BD, defined as recurrent and brief periods of elevation and activation that did not meet syndromal mania or hypomania criteria. All participants had at least one first- or second-degree family member with a history of BD I or II. Following a period of evaluation, participants were randomly assigned to one of two 4-month psychological therapies: Family-focused therapy (12 sessions of psychoeducation, communication training, and problem-solving skills training) or enhanced usual care (6 sessions of family and individual psychoeducation and support). They also received pharmacological management from study-affiliated psychiatrists when warranted.

We measured mood instability at intake and every 4-6 months over an average of 2 years (range 0-255 weeks). We used a brief parent questionnaire – the Children’s Affective Lability Scale⁴ – which enables measurement of lability on the dimensions of elevation or activation (e.g., bursts of silliness or hilarity, excessive familiarity with others), irritability (e.g., temper outbursts), or anxious-depression (e.g., sudden bouts of crying).

Over the 1- to 4-year period of follow-up, mood instability was associated with poor prognosis indicators in high-risk youth: Being younger, having younger ages at first symptom onset, being diagnosed with other specified BD (vs. major depression), and having more complex patterns of comorbid disorders. Mood instability tracked closely with levels of mania, depression, and global functioning over the follow-up. There was a temporal pathway between a diagnosis of other specified bipolar disorder at intake and higher levels of mood instability at follow-up, which in turn predicted higher levels of parent/child conflict. High levels of mood lability may lead to isolation from peers and tension within family relationships, which may fuel further children’s expressions of frustration, rage, depression, or impulsive behavior.

Youth with higher levels of mood instability required more complex medication regimens over 1 year than did those with lower instability. There was an overall reduction in mood instability as children aged (or spent more time in treatment). Over the 1- to 4-year follow-up, family-focused therapy was associated with longer intervals prior to new mood episodes than was enhanced usual care, but reductions in mood instability were independent of the type of psychosocial treatment assigned to children.

The participants in this study could not be followed long enough to determine whether levels of mood instability were associated with the later development of syndromal BD. Other studies, however, have documented this relationship. Large-scale longitudinal studies of high-risk children find that measures of mood lability – along with early onset manic symptoms, depression, anxiety, and a family history of mania or hypomania – can be combined to calculate the risk that any individual child will develop BD I or II over the next 5-8 years.^2,5

Clinicians should include measurement of the severity and psychosocial determinants of persistent mood shifts in youth under their care, particularly those with a family history of BD. Mood instability is associated with more severe symptom trajectories, more social isolation, and greater distress and conflict within the family. It may require a greater intensity of both pharmacological and psychosocial treatments to treat existing symptoms and functional impairments, and to prevent further mood deterioration.

Dr. Miklowitz is Distinguished Professor of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Semel Institute for Neuroscience and Human Behavior. He is the author of “The Bipolar Disorder Survival Guide, 3rd Ed.” (New York: Guilford Press, 2019) and “Bipolar Disorder: A Family-Focused Treatment Approach, 2nd Ed” (New York: Guilford Press, 2010). He has no conflicts of interest to disclose. Contact Dr. Miklowitz at [email protected].

References

1. Bonsall MB, et al. Nonlinear time-series approaches in characterizing mood stability and mood instability in bipolar disorder. Proc Biol Sci. Mar 7 2012;279(1730):916-24. doi: 10.1098/rspb.2011.1246.

2. Hafeman DM, et al. Toward the definition of a bipolar prodrome: Dimensional predictors of bipolar spectrum disorders in at-risk youths. Am J Psychiatry. 2016;173(7):695-704. doi: 10.1176/appi.ajp.2015.15040414.

3. Miklowitz DJ, et al. Mood instability in youth at high risk for bipolar disorder. J Am Acad Child Adol Psychiatry. 2022 Mar 17;S0890-8567(22)00118-6. doi: 10.1016/j.jaac.2022.03.009.

4. Gerson AC, et al. The Children’s Affective Lability Scale: a psychometric evaluation of reliability. Psychiatry Res. Dec 20 1996;65(3):189-98. doi: 10.1016/s0165-1781(96)02851-x.

5. Birmaher B, et al. A risk calculator to predict the individual risk of conversion from subthreshold bipolar symptoms to bipolar disorder I or II in youth. J Am Acad Child Adol Psychiatry. 2018;57(10):755-63. doi: 10.1016/j.jaac.2018.05.023.

Mood instability, or sudden, unpredictable, and frequent shifts in emotional states, characterizes many types of psychiatric disorder, including attention-deficit/hyperactivity disorder (ADHD), personality disorders, depression, and posttraumatic stress disorder. To say that individuals with bipolar disorder (BD) have mood instability sounds like a tautology. Nonetheless, mood instability has particular relevance to BD: Many patients have irregular or labile moods even when they are between major episodes of mania and depression.¹

Children of parents with BD who have high levels of mood instability are at particularly high risk for developing BD (types I or II) in late adolescence or early adulthood.² The following case provides an illustration:

Patrick, age 14, entered treatment with diagnoses of ADHD and other specified bipolar disorder. His mother felt that his behavior resembled that of his father, who had been treated for manic episodes. During the COVID-19 pandemic, Patrick had become increasingly difficult at home, with significant oppositionality, impulsive behavior, and difficulty following through on school assignments or household tasks. His mother’s most significant complaints concerned Patrick’s sudden outbursts of anger and abrupt verbal abuse when she asked him to stop playing video games. When interrupted, he cursed loudly and sometimes turned violent; he had broken a window and a door at home and had on one occasion physically attacked his younger brother. Patrick agreed that he became angry at times, but felt that others provoked him. When queried about depression, he described anxiety and worry. He was unable to describe a particular trigger for his anxiety except for being interrupted in online games with his friends, which made him “feel like a total loser.”

His mother reported that Patrick had multiple 1- to 2-day intervals in which he became “really silly, laughing at nothing,” talking rapidly, jumping from one topic to another, and becoming annoyed when others didn’t share his enthusiasm. In these activated intervals, he slept little and seemed to be full of energy; his mother would hear him talking loudly into his phone throughout the night. During one such interval he had become verbally aggressive with a peer, which had ruined their friendship. Both Patrick and his mother reported that they had been fighting constantly and, in her words, “our house has become a war zone.”

In our recent article in the Journal of the American Academy of Child and Adolescent Psychiatry,³ my coauthors and I examined the association between parents’ ratings of mood instability and clinicians’ longitudinal ratings of symptoms and functioning among youth (ages 9-17 years) who were at high risk for BD. The participants met DSM-5 diagnostic criteria for major depressive disorder or other specified BD, defined as recurrent and brief periods of elevation and activation that did not meet syndromal mania or hypomania criteria. All participants had at least one first- or second-degree family member with a history of BD I or II. Following a period of evaluation, participants were randomly assigned to one of two 4-month psychological therapies: Family-focused therapy (12 sessions of psychoeducation, communication training, and problem-solving skills training) or enhanced usual care (6 sessions of family and individual psychoeducation and support). They also received pharmacological management from study-affiliated psychiatrists when warranted.

We measured mood instability at intake and every 4-6 months over an average of 2 years (range 0-255 weeks). We used a brief parent questionnaire – the Children’s Affective Lability Scale⁴ – which enables measurement of lability on the dimensions of elevation or activation (e.g., bursts of silliness or hilarity, excessive familiarity with others), irritability (e.g., temper outbursts), or anxious-depression (e.g., sudden bouts of crying).

Over the 1- to 4-year period of follow-up, mood instability was associated with poor prognosis indicators in high-risk youth: Being younger, having younger ages at first symptom onset, being diagnosed with other specified BD (vs. major depression), and having more complex patterns of comorbid disorders. Mood instability tracked closely with levels of mania, depression, and global functioning over the follow-up. There was a temporal pathway between a diagnosis of other specified bipolar disorder at intake and higher levels of mood instability at follow-up, which in turn predicted higher levels of parent/child conflict. High levels of mood lability may lead to isolation from peers and tension within family relationships, which may fuel further children’s expressions of frustration, rage, depression, or impulsive behavior.

Youth with higher levels of mood instability required more complex medication regimens over 1 year than did those with lower instability. There was an overall reduction in mood instability as children aged (or spent more time in treatment). Over the 1- to 4-year follow-up, family-focused therapy was associated with longer intervals prior to new mood episodes than was enhanced usual care, but reductions in mood instability were independent of the type of psychosocial treatment assigned to children.

The participants in this study could not be followed long enough to determine whether levels of mood instability were associated with the later development of syndromal BD. Other studies, however, have documented this relationship. Large-scale longitudinal studies of high-risk children find that measures of mood lability – along with early onset manic symptoms, depression, anxiety, and a family history of mania or hypomania – can be combined to calculate the risk that any individual child will develop BD I or II over the next 5-8 years.^2,5

Clinicians should include measurement of the severity and psychosocial determinants of persistent mood shifts in youth under their care, particularly those with a family history of BD. Mood instability is associated with more severe symptom trajectories, more social isolation, and greater distress and conflict within the family. It may require a greater intensity of both pharmacological and psychosocial treatments to treat existing symptoms and functional impairments, and to prevent further mood deterioration.

Dr. Miklowitz is Distinguished Professor of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Semel Institute for Neuroscience and Human Behavior. He is the author of “The Bipolar Disorder Survival Guide, 3rd Ed.” (New York: Guilford Press, 2019) and “Bipolar Disorder: A Family-Focused Treatment Approach, 2nd Ed” (New York: Guilford Press, 2010). He has no conflicts of interest to disclose. Contact Dr. Miklowitz at [email protected].

References

1. Bonsall MB, et al. Nonlinear time-series approaches in characterizing mood stability and mood instability in bipolar disorder. Proc Biol Sci. Mar 7 2012;279(1730):916-24. doi: 10.1098/rspb.2011.1246.

2. Hafeman DM, et al. Toward the definition of a bipolar prodrome: Dimensional predictors of bipolar spectrum disorders in at-risk youths. Am J Psychiatry. 2016;173(7):695-704. doi: 10.1176/appi.ajp.2015.15040414.

3. Miklowitz DJ, et al. Mood instability in youth at high risk for bipolar disorder. J Am Acad Child Adol Psychiatry. 2022 Mar 17;S0890-8567(22)00118-6. doi: 10.1016/j.jaac.2022.03.009.

4. Gerson AC, et al. The Children’s Affective Lability Scale: a psychometric evaluation of reliability. Psychiatry Res. Dec 20 1996;65(3):189-98. doi: 10.1016/s0165-1781(96)02851-x.

5. Birmaher B, et al. A risk calculator to predict the individual risk of conversion from subthreshold bipolar symptoms to bipolar disorder I or II in youth. J Am Acad Child Adol Psychiatry. 2018;57(10):755-63. doi: 10.1016/j.jaac.2018.05.023.

Mood instability, or sudden, unpredictable, and frequent shifts in emotional states, characterizes many types of psychiatric disorder, including attention-deficit/hyperactivity disorder (ADHD), personality disorders, depression, and posttraumatic stress disorder. To say that individuals with bipolar disorder (BD) have mood instability sounds like a tautology. Nonetheless, mood instability has particular relevance to BD: Many patients have irregular or labile moods even when they are between major episodes of mania and depression.¹

Children of parents with BD who have high levels of mood instability are at particularly high risk for developing BD (types I or II) in late adolescence or early adulthood.² The following case provides an illustration:

Patrick, age 14, entered treatment with diagnoses of ADHD and other specified bipolar disorder. His mother felt that his behavior resembled that of his father, who had been treated for manic episodes. During the COVID-19 pandemic, Patrick had become increasingly difficult at home, with significant oppositionality, impulsive behavior, and difficulty following through on school assignments or household tasks. His mother’s most significant complaints concerned Patrick’s sudden outbursts of anger and abrupt verbal abuse when she asked him to stop playing video games. When interrupted, he cursed loudly and sometimes turned violent; he had broken a window and a door at home and had on one occasion physically attacked his younger brother. Patrick agreed that he became angry at times, but felt that others provoked him. When queried about depression, he described anxiety and worry. He was unable to describe a particular trigger for his anxiety except for being interrupted in online games with his friends, which made him “feel like a total loser.”

His mother reported that Patrick had multiple 1- to 2-day intervals in which he became “really silly, laughing at nothing,” talking rapidly, jumping from one topic to another, and becoming annoyed when others didn’t share his enthusiasm. In these activated intervals, he slept little and seemed to be full of energy; his mother would hear him talking loudly into his phone throughout the night. During one such interval he had become verbally aggressive with a peer, which had ruined their friendship. Both Patrick and his mother reported that they had been fighting constantly and, in her words, “our house has become a war zone.”

In our recent article in the Journal of the American Academy of Child and Adolescent Psychiatry,³ my coauthors and I examined the association between parents’ ratings of mood instability and clinicians’ longitudinal ratings of symptoms and functioning among youth (ages 9-17 years) who were at high risk for BD. The participants met DSM-5 diagnostic criteria for major depressive disorder or other specified BD, defined as recurrent and brief periods of elevation and activation that did not meet syndromal mania or hypomania criteria. All participants had at least one first- or second-degree family member with a history of BD I or II. Following a period of evaluation, participants were randomly assigned to one of two 4-month psychological therapies: Family-focused therapy (12 sessions of psychoeducation, communication training, and problem-solving skills training) or enhanced usual care (6 sessions of family and individual psychoeducation and support). They also received pharmacological management from study-affiliated psychiatrists when warranted.

We measured mood instability at intake and every 4-6 months over an average of 2 years (range 0-255 weeks). We used a brief parent questionnaire – the Children’s Affective Lability Scale⁴ – which enables measurement of lability on the dimensions of elevation or activation (e.g., bursts of silliness or hilarity, excessive familiarity with others), irritability (e.g., temper outbursts), or anxious-depression (e.g., sudden bouts of crying).

Over the 1- to 4-year period of follow-up, mood instability was associated with poor prognosis indicators in high-risk youth: Being younger, having younger ages at first symptom onset, being diagnosed with other specified BD (vs. major depression), and having more complex patterns of comorbid disorders. Mood instability tracked closely with levels of mania, depression, and global functioning over the follow-up. There was a temporal pathway between a diagnosis of other specified bipolar disorder at intake and higher levels of mood instability at follow-up, which in turn predicted higher levels of parent/child conflict. High levels of mood lability may lead to isolation from peers and tension within family relationships, which may fuel further children’s expressions of frustration, rage, depression, or impulsive behavior.

Youth with higher levels of mood instability required more complex medication regimens over 1 year than did those with lower instability. There was an overall reduction in mood instability as children aged (or spent more time in treatment). Over the 1- to 4-year follow-up, family-focused therapy was associated with longer intervals prior to new mood episodes than was enhanced usual care, but reductions in mood instability were independent of the type of psychosocial treatment assigned to children.

The participants in this study could not be followed long enough to determine whether levels of mood instability were associated with the later development of syndromal BD. Other studies, however, have documented this relationship. Large-scale longitudinal studies of high-risk children find that measures of mood lability – along with early onset manic symptoms, depression, anxiety, and a family history of mania or hypomania – can be combined to calculate the risk that any individual child will develop BD I or II over the next 5-8 years.^2,5

Clinicians should include measurement of the severity and psychosocial determinants of persistent mood shifts in youth under their care, particularly those with a family history of BD. Mood instability is associated with more severe symptom trajectories, more social isolation, and greater distress and conflict within the family. It may require a greater intensity of both pharmacological and psychosocial treatments to treat existing symptoms and functional impairments, and to prevent further mood deterioration.

Dr. Miklowitz is Distinguished Professor of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Semel Institute for Neuroscience and Human Behavior. He is the author of “The Bipolar Disorder Survival Guide, 3rd Ed.” (New York: Guilford Press, 2019) and “Bipolar Disorder: A Family-Focused Treatment Approach, 2nd Ed” (New York: Guilford Press, 2010). He has no conflicts of interest to disclose. Contact Dr. Miklowitz at [email protected].

References

1. Bonsall MB, et al. Nonlinear time-series approaches in characterizing mood stability and mood instability in bipolar disorder. Proc Biol Sci. Mar 7 2012;279(1730):916-24. doi: 10.1098/rspb.2011.1246.

2. Hafeman DM, et al. Toward the definition of a bipolar prodrome: Dimensional predictors of bipolar spectrum disorders in at-risk youths. Am J Psychiatry. 2016;173(7):695-704. doi: 10.1176/appi.ajp.2015.15040414.

3. Miklowitz DJ, et al. Mood instability in youth at high risk for bipolar disorder. J Am Acad Child Adol Psychiatry. 2022 Mar 17;S0890-8567(22)00118-6. doi: 10.1016/j.jaac.2022.03.009.

4. Gerson AC, et al. The Children’s Affective Lability Scale: a psychometric evaluation of reliability. Psychiatry Res. Dec 20 1996;65(3):189-98. doi: 10.1016/s0165-1781(96)02851-x.

5. Birmaher B, et al. A risk calculator to predict the individual risk of conversion from subthreshold bipolar symptoms to bipolar disorder I or II in youth. J Am Acad Child Adol Psychiatry. 2018;57(10):755-63. doi: 10.1016/j.jaac.2018.05.023.

The newly released global estimate is now 25 million children (2 million more than in 2020) missing scheduled vaccines. This continues to bode badly for multiple vaccine-preventable infections, but maybe the most for measles in 2022. 

Specifically for measles vaccine, global two-dose coverage was only 71%. Coverage was less than 50% in 8 countries: ​Chad, Guinea,​ Samoa, North Korea, Central African Republic, Somalia, Angola, and South Sudan. These eight areas seem ripe for outbreaks this year and indeed Somalia is having an outbreak. 

Overall, worldwide measles cases increased 79% in early 2022, compared with 2021. The top 10 countries for measles cases from November 2021 to April 2022, per the World Health Organization, include Nigeria, India, Soma Ethiopia, Pakistan, DR Congo, Afghanistan, Liberia, Cameroon, and Ivory Coast.

In the United States, we have been lucky so far with only 55 cases since the start of 2021. However, MMR two-dose coverage has dropped since the pandemic’s start. The list of U.S. areas with the lowest overall two-dose MMR coverage as of 2021 were D.C. (78.9%), Houston (93.7%), Idaho (86.5%), Wisconsin (87.2%), Maryland (87.6%), Georgia (88.5%), Kentucky (88.9%), Ohio (89.6%), and Minnesota (89.8%). Only 14 states had rates over the targeted 95% rate needed for community (herd) immunity against measles (MMWR Morb Mortal Wkly Rep. 2022;71:561-8).  

Two bits of good news are that there seems to be some catch-up occurring in vaccine uptake overall (including MMR) and we now have two MMR suppliers in the United States since GlaxoSmithKline’s MMR was recently approved by the Food and Drug Administration for persons over 1 year of age. Let’s all redouble our efforts at adding to the catch-up efforts. 

Christopher J. Harrison, MD, is professor, University of Missouri Kansas City School of Medicine, department of medicine, infectious diseases section, Kansas City. He has no financial conflicts of interest.

The newly released global estimate is now 25 million children (2 million more than in 2020) missing scheduled vaccines. This continues to bode badly for multiple vaccine-preventable infections, but maybe the most for measles in 2022. 

Specifically for measles vaccine, global two-dose coverage was only 71%. Coverage was less than 50% in 8 countries: ​Chad, Guinea,​ Samoa, North Korea, Central African Republic, Somalia, Angola, and South Sudan. These eight areas seem ripe for outbreaks this year and indeed Somalia is having an outbreak. 

Overall, worldwide measles cases increased 79% in early 2022, compared with 2021. The top 10 countries for measles cases from November 2021 to April 2022, per the World Health Organization, include Nigeria, India, Soma Ethiopia, Pakistan, DR Congo, Afghanistan, Liberia, Cameroon, and Ivory Coast.

In the United States, we have been lucky so far with only 55 cases since the start of 2021. However, MMR two-dose coverage has dropped since the pandemic’s start. The list of U.S. areas with the lowest overall two-dose MMR coverage as of 2021 were D.C. (78.9%), Houston (93.7%), Idaho (86.5%), Wisconsin (87.2%), Maryland (87.6%), Georgia (88.5%), Kentucky (88.9%), Ohio (89.6%), and Minnesota (89.8%). Only 14 states had rates over the targeted 95% rate needed for community (herd) immunity against measles (MMWR Morb Mortal Wkly Rep. 2022;71:561-8).  

Two bits of good news are that there seems to be some catch-up occurring in vaccine uptake overall (including MMR) and we now have two MMR suppliers in the United States since GlaxoSmithKline’s MMR was recently approved by the Food and Drug Administration for persons over 1 year of age. Let’s all redouble our efforts at adding to the catch-up efforts. 

Christopher J. Harrison, MD, is professor, University of Missouri Kansas City School of Medicine, department of medicine, infectious diseases section, Kansas City. He has no financial conflicts of interest.

The newly released global estimate is now 25 million children (2 million more than in 2020) missing scheduled vaccines. This continues to bode badly for multiple vaccine-preventable infections, but maybe the most for measles in 2022. 

Specifically for measles vaccine, global two-dose coverage was only 71%. Coverage was less than 50% in 8 countries: ​Chad, Guinea,​ Samoa, North Korea, Central African Republic, Somalia, Angola, and South Sudan. These eight areas seem ripe for outbreaks this year and indeed Somalia is having an outbreak. 

Overall, worldwide measles cases increased 79% in early 2022, compared with 2021. The top 10 countries for measles cases from November 2021 to April 2022, per the World Health Organization, include Nigeria, India, Soma Ethiopia, Pakistan, DR Congo, Afghanistan, Liberia, Cameroon, and Ivory Coast.

In the United States, we have been lucky so far with only 55 cases since the start of 2021. However, MMR two-dose coverage has dropped since the pandemic’s start. The list of U.S. areas with the lowest overall two-dose MMR coverage as of 2021 were D.C. (78.9%), Houston (93.7%), Idaho (86.5%), Wisconsin (87.2%), Maryland (87.6%), Georgia (88.5%), Kentucky (88.9%), Ohio (89.6%), and Minnesota (89.8%). Only 14 states had rates over the targeted 95% rate needed for community (herd) immunity against measles (MMWR Morb Mortal Wkly Rep. 2022;71:561-8).  

Two bits of good news are that there seems to be some catch-up occurring in vaccine uptake overall (including MMR) and we now have two MMR suppliers in the United States since GlaxoSmithKline’s MMR was recently approved by the Food and Drug Administration for persons over 1 year of age. Let’s all redouble our efforts at adding to the catch-up efforts. 

Christopher J. Harrison, MD, is professor, University of Missouri Kansas City School of Medicine, department of medicine, infectious diseases section, Kansas City. He has no financial conflicts of interest.

“It was my wife’s walker, and I’ve never used one before. Sorry that I keep bumping into things.”

He was in his early 70s, recently widowed. He hadn’t needed a walker until yesterday, and his son had gotten it out of the garage where they’d just stowed it away. I showed him how to change the height setting on it so he didn’t have to lean so far over.

His daughter was a longstanding patient of mine, and now she and her brother were worried about their dad. He’d been so healthy for years, taking care of their mother as she declined with cancer. Now, 2 months since her death, he’d started going downhill. He’d been, understandably, depressed and had lost some weight. A few weeks ago he’d had some nonspecific upper respiratory crud, and now they were worried he wasn’t eating. He’d gotten progressively weaker in the last few days, leading to their getting out the walker.

I knew my patient for several years. She wasn’t given to panicking, and was worried about her dad. By this time, I was too. Twenty-eight years of neurology training and practice puts you on the edge for some things. The “Spidey Sense,” as I’ve always called it, was tingling.

It took a very quick neurologic exam to find what I needed. He was indeed weak, had decreased distal sensation, and was completely areflexic. It was time to take the most-dreaded outpatient neurology gamble: The direct office-to-ER admission.

I told his daughter to take him to the nearby ER and scribbled a note that said “Probable Guillain-Barré. Needs urgent workup.” They were somewhat taken aback, as they had dinner plans that night, but his daughter knew me well enough to know that I don’t pull fire alarms for fun.

As soon as they’d left I called the ER doctor and told her what was coming. My hospital days ended 2 years ago, but I wanted to do everything I could to make sure the right ball was rolling.

Then my part was over. I had other patients waiting, tests to review, phone calls to make.

This is where the anxiety began. Nobody wants to be the person who cries wolf, or admits “dumps.” I’ve been on both sides of admissions, and bashing outpatient docs for unnecessary hospital referrals is a perennial pastime of inpatient care.

I was sure of my actions, but as the hours crept by some doubt came in. What if he got to the hospital and suddenly wasn’t weak? Or it was all from a medication error he’d made at home?

No one wants to claim they saw a flare when there wasn’t one, or get the reputation of being past their game. I was worried about the patient, but also began to worry I’d screwed up and missed something else.

I finished the day and went home. After closing out my usual end-of-the-day stuff I logged into the hospital system to see what was going on.

Normal cervical spine MRI. Spinal fluid had zero cells and elevated protein.

I breathed a sigh of relief and relaxed back into my chair. I’d made the right call. The hospital neurologist had ordered IVIG. The patient would hopefully recover. No one would think I’d screwed up a potentially serious case. And, somewhere in the back of my mind, the Sherlock Holmes inside every neurologist tipped his deerstalker cap at me and gave a slight nod.

There’s the relief of having done the right thing for the patient, having made the correct diagnosis, and, at the end of the day, being reassured that (some days at least) I still know what I’m doing.

It’s those feelings that brought me here and still keep me going.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

“It was my wife’s walker, and I’ve never used one before. Sorry that I keep bumping into things.”

He was in his early 70s, recently widowed. He hadn’t needed a walker until yesterday, and his son had gotten it out of the garage where they’d just stowed it away. I showed him how to change the height setting on it so he didn’t have to lean so far over.

His daughter was a longstanding patient of mine, and now she and her brother were worried about their dad. He’d been so healthy for years, taking care of their mother as she declined with cancer. Now, 2 months since her death, he’d started going downhill. He’d been, understandably, depressed and had lost some weight. A few weeks ago he’d had some nonspecific upper respiratory crud, and now they were worried he wasn’t eating. He’d gotten progressively weaker in the last few days, leading to their getting out the walker.

I knew my patient for several years. She wasn’t given to panicking, and was worried about her dad. By this time, I was too. Twenty-eight years of neurology training and practice puts you on the edge for some things. The “Spidey Sense,” as I’ve always called it, was tingling.

It took a very quick neurologic exam to find what I needed. He was indeed weak, had decreased distal sensation, and was completely areflexic. It was time to take the most-dreaded outpatient neurology gamble: The direct office-to-ER admission.

I told his daughter to take him to the nearby ER and scribbled a note that said “Probable Guillain-Barré. Needs urgent workup.” They were somewhat taken aback, as they had dinner plans that night, but his daughter knew me well enough to know that I don’t pull fire alarms for fun.

As soon as they’d left I called the ER doctor and told her what was coming. My hospital days ended 2 years ago, but I wanted to do everything I could to make sure the right ball was rolling.

Then my part was over. I had other patients waiting, tests to review, phone calls to make.

This is where the anxiety began. Nobody wants to be the person who cries wolf, or admits “dumps.” I’ve been on both sides of admissions, and bashing outpatient docs for unnecessary hospital referrals is a perennial pastime of inpatient care.

I was sure of my actions, but as the hours crept by some doubt came in. What if he got to the hospital and suddenly wasn’t weak? Or it was all from a medication error he’d made at home?

No one wants to claim they saw a flare when there wasn’t one, or get the reputation of being past their game. I was worried about the patient, but also began to worry I’d screwed up and missed something else.

I finished the day and went home. After closing out my usual end-of-the-day stuff I logged into the hospital system to see what was going on.

Normal cervical spine MRI. Spinal fluid had zero cells and elevated protein.

I breathed a sigh of relief and relaxed back into my chair. I’d made the right call. The hospital neurologist had ordered IVIG. The patient would hopefully recover. No one would think I’d screwed up a potentially serious case. And, somewhere in the back of my mind, the Sherlock Holmes inside every neurologist tipped his deerstalker cap at me and gave a slight nod.

There’s the relief of having done the right thing for the patient, having made the correct diagnosis, and, at the end of the day, being reassured that (some days at least) I still know what I’m doing.

It’s those feelings that brought me here and still keep me going.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

“It was my wife’s walker, and I’ve never used one before. Sorry that I keep bumping into things.”

He was in his early 70s, recently widowed. He hadn’t needed a walker until yesterday, and his son had gotten it out of the garage where they’d just stowed it away. I showed him how to change the height setting on it so he didn’t have to lean so far over.

His daughter was a longstanding patient of mine, and now she and her brother were worried about their dad. He’d been so healthy for years, taking care of their mother as she declined with cancer. Now, 2 months since her death, he’d started going downhill. He’d been, understandably, depressed and had lost some weight. A few weeks ago he’d had some nonspecific upper respiratory crud, and now they were worried he wasn’t eating. He’d gotten progressively weaker in the last few days, leading to their getting out the walker.

I knew my patient for several years. She wasn’t given to panicking, and was worried about her dad. By this time, I was too. Twenty-eight years of neurology training and practice puts you on the edge for some things. The “Spidey Sense,” as I’ve always called it, was tingling.

It took a very quick neurologic exam to find what I needed. He was indeed weak, had decreased distal sensation, and was completely areflexic. It was time to take the most-dreaded outpatient neurology gamble: The direct office-to-ER admission.

I told his daughter to take him to the nearby ER and scribbled a note that said “Probable Guillain-Barré. Needs urgent workup.” They were somewhat taken aback, as they had dinner plans that night, but his daughter knew me well enough to know that I don’t pull fire alarms for fun.

As soon as they’d left I called the ER doctor and told her what was coming. My hospital days ended 2 years ago, but I wanted to do everything I could to make sure the right ball was rolling.

Then my part was over. I had other patients waiting, tests to review, phone calls to make.

This is where the anxiety began. Nobody wants to be the person who cries wolf, or admits “dumps.” I’ve been on both sides of admissions, and bashing outpatient docs for unnecessary hospital referrals is a perennial pastime of inpatient care.

I was sure of my actions, but as the hours crept by some doubt came in. What if he got to the hospital and suddenly wasn’t weak? Or it was all from a medication error he’d made at home?

No one wants to claim they saw a flare when there wasn’t one, or get the reputation of being past their game. I was worried about the patient, but also began to worry I’d screwed up and missed something else.

I finished the day and went home. After closing out my usual end-of-the-day stuff I logged into the hospital system to see what was going on.

Normal cervical spine MRI. Spinal fluid had zero cells and elevated protein.

I breathed a sigh of relief and relaxed back into my chair. I’d made the right call. The hospital neurologist had ordered IVIG. The patient would hopefully recover. No one would think I’d screwed up a potentially serious case. And, somewhere in the back of my mind, the Sherlock Holmes inside every neurologist tipped his deerstalker cap at me and gave a slight nod.

There’s the relief of having done the right thing for the patient, having made the correct diagnosis, and, at the end of the day, being reassured that (some days at least) I still know what I’m doing.

It’s those feelings that brought me here and still keep me going.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

This study of antibiotic use in the first 2 years of life in a reasonably standardized primary care office raises issues about antibiotic stewardship that can be the basis for counseling against antibiotics for viral infections or mild uncomplicated acute otitis media (AOM) above 6 months of age. Even unintended and previously undescribed downstream effects of antibiotics should play a role in our decisions and are another nudge toward prudent antibiotic use – for example, watchful waiting (WW) for AOM. 

Some families ask for antibiotics for almost any infection while others may want antibiotics only if really necessary. But maybe patient family wishes are not the main driver, considering a report in Pediatrics (2022;150[1]:e2021055613). They analyzed over 2 million AOM episodes from billing/enrollment records from the MarketScan commercial claims research databases. They reported that, despite WW being the management of choice per American Academy of Pediatrics guidelines for uncomplicated AOM in children over 1 year of age, WW use had not increased between 2015 and 2019. Further, they noted that WW was not related to patient factors or demographics but was associated with specialty and provider. For example, WW use was five times more likely by otolaryngologists than pediatricians and less likely by nonpediatricians than pediatricians. Further, some clinicians used WW a lot, while others almost not at all (high-volume antibiotic prescribers). Of note, having a fever significantly lowered the chance of WW.

Maturing data on antibiotic-related alterations in species distribution and quantity within children’s microbiome plus potential effects on antibody responses to vaccines are ideas families need to hear. I suggest sharing these as part of anticipatory guidance at well-child checks as early in life as is feasible. 

Christopher J. Harrison, MD, is professor, University of Missouri Kansas City School of Medicine, department of medicine, infectious diseases section, Kansas City. He has no financial conflicts of interest.

This study of antibiotic use in the first 2 years of life in a reasonably standardized primary care office raises issues about antibiotic stewardship that can be the basis for counseling against antibiotics for viral infections or mild uncomplicated acute otitis media (AOM) above 6 months of age. Even unintended and previously undescribed downstream effects of antibiotics should play a role in our decisions and are another nudge toward prudent antibiotic use – for example, watchful waiting (WW) for AOM. 

Some families ask for antibiotics for almost any infection while others may want antibiotics only if really necessary. But maybe patient family wishes are not the main driver, considering a report in Pediatrics (2022;150[1]:e2021055613). They analyzed over 2 million AOM episodes from billing/enrollment records from the MarketScan commercial claims research databases. They reported that, despite WW being the management of choice per American Academy of Pediatrics guidelines for uncomplicated AOM in children over 1 year of age, WW use had not increased between 2015 and 2019. Further, they noted that WW was not related to patient factors or demographics but was associated with specialty and provider. For example, WW use was five times more likely by otolaryngologists than pediatricians and less likely by nonpediatricians than pediatricians. Further, some clinicians used WW a lot, while others almost not at all (high-volume antibiotic prescribers). Of note, having a fever significantly lowered the chance of WW.

Maturing data on antibiotic-related alterations in species distribution and quantity within children’s microbiome plus potential effects on antibody responses to vaccines are ideas families need to hear. I suggest sharing these as part of anticipatory guidance at well-child checks as early in life as is feasible. 

Christopher J. Harrison, MD, is professor, University of Missouri Kansas City School of Medicine, department of medicine, infectious diseases section, Kansas City. He has no financial conflicts of interest.

This study of antibiotic use in the first 2 years of life in a reasonably standardized primary care office raises issues about antibiotic stewardship that can be the basis for counseling against antibiotics for viral infections or mild uncomplicated acute otitis media (AOM) above 6 months of age. Even unintended and previously undescribed downstream effects of antibiotics should play a role in our decisions and are another nudge toward prudent antibiotic use – for example, watchful waiting (WW) for AOM. 

Some families ask for antibiotics for almost any infection while others may want antibiotics only if really necessary. But maybe patient family wishes are not the main driver, considering a report in Pediatrics (2022;150[1]:e2021055613). They analyzed over 2 million AOM episodes from billing/enrollment records from the MarketScan commercial claims research databases. They reported that, despite WW being the management of choice per American Academy of Pediatrics guidelines for uncomplicated AOM in children over 1 year of age, WW use had not increased between 2015 and 2019. Further, they noted that WW was not related to patient factors or demographics but was associated with specialty and provider. For example, WW use was five times more likely by otolaryngologists than pediatricians and less likely by nonpediatricians than pediatricians. Further, some clinicians used WW a lot, while others almost not at all (high-volume antibiotic prescribers). Of note, having a fever significantly lowered the chance of WW.

Maturing data on antibiotic-related alterations in species distribution and quantity within children’s microbiome plus potential effects on antibody responses to vaccines are ideas families need to hear. I suggest sharing these as part of anticipatory guidance at well-child checks as early in life as is feasible. 

Christopher J. Harrison, MD, is professor, University of Missouri Kansas City School of Medicine, department of medicine, infectious diseases section, Kansas City. He has no financial conflicts of interest.

In this column I have previously discussed the microbiome and its importance to health, especially as it relates to infections in children. Given the appreciated connection between microbiome and immunity, my group in Rochester, N.Y., recently undertook a study of the effect of antibiotic usage on the immune response to routine early childhood vaccines. In mouse models, it was previously shown that antibiotic exposure induced a reduction in the abundance and diversity of gut microbiota that in turn negatively affected the generation and maintenance of vaccine-induced immunity.^1,2 A study from Stanford University was the first experimental human trial of antibiotic effects on vaccine responses. Adult volunteers were given an antibiotic or not before seasonal influenza vaccination and the researchers identified specific bacteria in the gut that were reduced by the antibiotics given. Those normal bacteria in the gut microbiome were shown to provide positive immunity signals to the systemic immune system that potentiated vaccine responses.³

My group conducted the first-ever study in children to explore whether an association existed between antibiotic use and vaccine-induced antibody levels. In the May issue of Pediatrics we report results from 560 children studied.⁴ From these children, 11,888 serum antibody levels to vaccine antigens were measured. Vaccine-induced antibody levels were determined at various time points after primary vaccination at child age 2, 4, and 6 months and boosters at age 12-18 months for 10 antigens included in four vaccines: DTaP, Hib, IPV, and PCV. The antibody levels to vaccine components were measured to DTaP (diphtheria toxoid, pertussis toxoid, tetanus toxoid, pertactin, and filamentous hemagglutinin), Hib conjugate (polyribosylribitol phosphate), IPV (polio 2), and PCV (serotypes 6B, 14, and 23F). A total of 342 children with 1,678 antibiotic courses prescribed were compared with 218 children with no antibiotic exposures. The predominant antibiotics prescribed were amoxicillin, cefdinir, amoxicillin/clavulanate, and ceftriaxone, since most treatments were for acute otitis media.

Of possible high clinical relevance, we found that from 9 to 24 months of age, children with antibiotic exposure had a higher frequency of vaccine-induced antibody levels below protection compared with children with no antibiotic use, placing them at risk of contracting a vaccine-preventable infection for DTaP antigens DT, TT, and PT and for PCV serotype 14.

For time points where antibody levels were determined within 30 days of completion of a course of antibiotics (recent antibiotic use), individual antibiotics were analyzed for effect on antibody levels below protective levels. Across all vaccine antigens measured, we found that all antibiotics had a negative effect on antibody levels and percentage of children achieving the protective antibody level threshold. Amoxicillin use had a lower association with lower antibody levels than the broader spectrum antibiotics, amoxicillin clavulanate (Augmentin), cefdinir, and ceftriaxone. For children receiving amoxicillin/clavulanate prescriptions, it was possible to compare the effect of shorter versus longer courses and we found that a 5-day course was associated with subprotective antibody levels similar to 10 days of amoxicillin, whereas 10-day amoxicillin/clavulanate was associated with higher frequency of children having subprotective antibody levels (Figure).

We examined whether accumulation of antibiotic courses in the first year of life had an association with subsequent vaccine-induced antibody levels and found that each antibiotic prescription was associated with a reduction in the median antibody level. For DTaP, each prescription was associated with 5.8% drop in antibody level to the vaccine components. For Hib the drop was 6.8%, IPV was 11.3%, and PCV was 10.4% – all statistically significant. To determine if booster vaccination influenced this association, a second analysis was performed using antibiotic prescriptions up to 15 months of age. We found each antibiotic prescription was associated with a reduction in median vaccine-induced antibody levels for DTaP by 18%, Hib by 21%, IPV by 19%, and PCV by 12% – all statistically significant.

Our study is the first in young children during the early age window where vaccine-induced immunity is established. Antibiotic use was associated with increased frequency of subprotective antibody levels for several vaccines used in children up to 2 years of age. The lower antibody levels could leave children vulnerable to vaccine preventable diseases. Perhaps outbreaks of vaccine-preventable diseases, such as pertussis, may be a consequence of multiple courses of antibiotics suppressing vaccine-induced immunity.

A goal of this study was to explore potential acute and long-term effects of antibiotic exposure on vaccine-induced antibody levels. Accumulated antibiotic courses up to booster immunization was associated with decreased vaccine antibody levels both before and after booster, suggesting that booster immunization was not sufficient to change the negative association with antibiotic exposure. The results were similar for all vaccines tested, suggesting that the specific vaccine formulation was not a factor.

The study has several limitations. The antibiotic prescription data and measurements of vaccine-induced antibody levels were recorded and measured prospectively; however, our analysis was done retrospectively. The group of study children was derived from my private practice in Rochester, N.Y., and may not be broadly representative of all children. The number of vaccine antibody measurements was limited by serum availability at some sampling time points in some children; and sometimes, the serum samples were collected far apart, which weakened our ability to perform longitudinal analyses. We did not collect stool samples from the children so we could not directly study the effect of antibiotic courses on the gut microbiome.

Our study adds new reasons to be cautious about overprescribing antibiotics on an individual child basis because an adverse effect extends to reduction in vaccine responses. This should be explained to parents requesting unnecessary antibiotics for colds and coughs. When antibiotics are necessary, the judicious choice of a narrow-spectrum antibiotic or a shorter duration of a broader spectrum antibiotic may reduce adverse effects on vaccine-induced immunity.

References

1. Valdez Y et al. Influence of the microbiota on vaccine effectiveness. Trends Immunol. 2014;35(11):526-37.

2. Lynn MA et al. Early-life antibiotic-driven dysbiosis leads to dysregulated vaccine immune responses in mice. Cell Host Microbe. 2018;23(5):653-60.e5.

3. Hagan T et al. Antibiotics-driven gut microbiome perturbation alters immunity to vaccines in humans. Cell. 2019;178(6):1313-28.e13.

4. Chapman T et al. Antibiotic use and vaccine antibody levels. Pediatrics. 2022;149(5);1-17. doi: 10.1542/peds.2021-052061.

In this column I have previously discussed the microbiome and its importance to health, especially as it relates to infections in children. Given the appreciated connection between microbiome and immunity, my group in Rochester, N.Y., recently undertook a study of the effect of antibiotic usage on the immune response to routine early childhood vaccines. In mouse models, it was previously shown that antibiotic exposure induced a reduction in the abundance and diversity of gut microbiota that in turn negatively affected the generation and maintenance of vaccine-induced immunity.^1,2 A study from Stanford University was the first experimental human trial of antibiotic effects on vaccine responses. Adult volunteers were given an antibiotic or not before seasonal influenza vaccination and the researchers identified specific bacteria in the gut that were reduced by the antibiotics given. Those normal bacteria in the gut microbiome were shown to provide positive immunity signals to the systemic immune system that potentiated vaccine responses.³

My group conducted the first-ever study in children to explore whether an association existed between antibiotic use and vaccine-induced antibody levels. In the May issue of Pediatrics we report results from 560 children studied.⁴ From these children, 11,888 serum antibody levels to vaccine antigens were measured. Vaccine-induced antibody levels were determined at various time points after primary vaccination at child age 2, 4, and 6 months and boosters at age 12-18 months for 10 antigens included in four vaccines: DTaP, Hib, IPV, and PCV. The antibody levels to vaccine components were measured to DTaP (diphtheria toxoid, pertussis toxoid, tetanus toxoid, pertactin, and filamentous hemagglutinin), Hib conjugate (polyribosylribitol phosphate), IPV (polio 2), and PCV (serotypes 6B, 14, and 23F). A total of 342 children with 1,678 antibiotic courses prescribed were compared with 218 children with no antibiotic exposures. The predominant antibiotics prescribed were amoxicillin, cefdinir, amoxicillin/clavulanate, and ceftriaxone, since most treatments were for acute otitis media.

Of possible high clinical relevance, we found that from 9 to 24 months of age, children with antibiotic exposure had a higher frequency of vaccine-induced antibody levels below protection compared with children with no antibiotic use, placing them at risk of contracting a vaccine-preventable infection for DTaP antigens DT, TT, and PT and for PCV serotype 14.

For time points where antibody levels were determined within 30 days of completion of a course of antibiotics (recent antibiotic use), individual antibiotics were analyzed for effect on antibody levels below protective levels. Across all vaccine antigens measured, we found that all antibiotics had a negative effect on antibody levels and percentage of children achieving the protective antibody level threshold. Amoxicillin use had a lower association with lower antibody levels than the broader spectrum antibiotics, amoxicillin clavulanate (Augmentin), cefdinir, and ceftriaxone. For children receiving amoxicillin/clavulanate prescriptions, it was possible to compare the effect of shorter versus longer courses and we found that a 5-day course was associated with subprotective antibody levels similar to 10 days of amoxicillin, whereas 10-day amoxicillin/clavulanate was associated with higher frequency of children having subprotective antibody levels (Figure).

We examined whether accumulation of antibiotic courses in the first year of life had an association with subsequent vaccine-induced antibody levels and found that each antibiotic prescription was associated with a reduction in the median antibody level. For DTaP, each prescription was associated with 5.8% drop in antibody level to the vaccine components. For Hib the drop was 6.8%, IPV was 11.3%, and PCV was 10.4% – all statistically significant. To determine if booster vaccination influenced this association, a second analysis was performed using antibiotic prescriptions up to 15 months of age. We found each antibiotic prescription was associated with a reduction in median vaccine-induced antibody levels for DTaP by 18%, Hib by 21%, IPV by 19%, and PCV by 12% – all statistically significant.

Our study is the first in young children during the early age window where vaccine-induced immunity is established. Antibiotic use was associated with increased frequency of subprotective antibody levels for several vaccines used in children up to 2 years of age. The lower antibody levels could leave children vulnerable to vaccine preventable diseases. Perhaps outbreaks of vaccine-preventable diseases, such as pertussis, may be a consequence of multiple courses of antibiotics suppressing vaccine-induced immunity.

A goal of this study was to explore potential acute and long-term effects of antibiotic exposure on vaccine-induced antibody levels. Accumulated antibiotic courses up to booster immunization was associated with decreased vaccine antibody levels both before and after booster, suggesting that booster immunization was not sufficient to change the negative association with antibiotic exposure. The results were similar for all vaccines tested, suggesting that the specific vaccine formulation was not a factor.

The study has several limitations. The antibiotic prescription data and measurements of vaccine-induced antibody levels were recorded and measured prospectively; however, our analysis was done retrospectively. The group of study children was derived from my private practice in Rochester, N.Y., and may not be broadly representative of all children. The number of vaccine antibody measurements was limited by serum availability at some sampling time points in some children; and sometimes, the serum samples were collected far apart, which weakened our ability to perform longitudinal analyses. We did not collect stool samples from the children so we could not directly study the effect of antibiotic courses on the gut microbiome.

Our study adds new reasons to be cautious about overprescribing antibiotics on an individual child basis because an adverse effect extends to reduction in vaccine responses. This should be explained to parents requesting unnecessary antibiotics for colds and coughs. When antibiotics are necessary, the judicious choice of a narrow-spectrum antibiotic or a shorter duration of a broader spectrum antibiotic may reduce adverse effects on vaccine-induced immunity.

References

1. Valdez Y et al. Influence of the microbiota on vaccine effectiveness. Trends Immunol. 2014;35(11):526-37.

2. Lynn MA et al. Early-life antibiotic-driven dysbiosis leads to dysregulated vaccine immune responses in mice. Cell Host Microbe. 2018;23(5):653-60.e5.

3. Hagan T et al. Antibiotics-driven gut microbiome perturbation alters immunity to vaccines in humans. Cell. 2019;178(6):1313-28.e13.

4. Chapman T et al. Antibiotic use and vaccine antibody levels. Pediatrics. 2022;149(5);1-17. doi: 10.1542/peds.2021-052061.

In this column I have previously discussed the microbiome and its importance to health, especially as it relates to infections in children. Given the appreciated connection between microbiome and immunity, my group in Rochester, N.Y., recently undertook a study of the effect of antibiotic usage on the immune response to routine early childhood vaccines. In mouse models, it was previously shown that antibiotic exposure induced a reduction in the abundance and diversity of gut microbiota that in turn negatively affected the generation and maintenance of vaccine-induced immunity.^1,2 A study from Stanford University was the first experimental human trial of antibiotic effects on vaccine responses. Adult volunteers were given an antibiotic or not before seasonal influenza vaccination and the researchers identified specific bacteria in the gut that were reduced by the antibiotics given. Those normal bacteria in the gut microbiome were shown to provide positive immunity signals to the systemic immune system that potentiated vaccine responses.³

My group conducted the first-ever study in children to explore whether an association existed between antibiotic use and vaccine-induced antibody levels. In the May issue of Pediatrics we report results from 560 children studied.⁴ From these children, 11,888 serum antibody levels to vaccine antigens were measured. Vaccine-induced antibody levels were determined at various time points after primary vaccination at child age 2, 4, and 6 months and boosters at age 12-18 months for 10 antigens included in four vaccines: DTaP, Hib, IPV, and PCV. The antibody levels to vaccine components were measured to DTaP (diphtheria toxoid, pertussis toxoid, tetanus toxoid, pertactin, and filamentous hemagglutinin), Hib conjugate (polyribosylribitol phosphate), IPV (polio 2), and PCV (serotypes 6B, 14, and 23F). A total of 342 children with 1,678 antibiotic courses prescribed were compared with 218 children with no antibiotic exposures. The predominant antibiotics prescribed were amoxicillin, cefdinir, amoxicillin/clavulanate, and ceftriaxone, since most treatments were for acute otitis media.

Of possible high clinical relevance, we found that from 9 to 24 months of age, children with antibiotic exposure had a higher frequency of vaccine-induced antibody levels below protection compared with children with no antibiotic use, placing them at risk of contracting a vaccine-preventable infection for DTaP antigens DT, TT, and PT and for PCV serotype 14.

For time points where antibody levels were determined within 30 days of completion of a course of antibiotics (recent antibiotic use), individual antibiotics were analyzed for effect on antibody levels below protective levels. Across all vaccine antigens measured, we found that all antibiotics had a negative effect on antibody levels and percentage of children achieving the protective antibody level threshold. Amoxicillin use had a lower association with lower antibody levels than the broader spectrum antibiotics, amoxicillin clavulanate (Augmentin), cefdinir, and ceftriaxone. For children receiving amoxicillin/clavulanate prescriptions, it was possible to compare the effect of shorter versus longer courses and we found that a 5-day course was associated with subprotective antibody levels similar to 10 days of amoxicillin, whereas 10-day amoxicillin/clavulanate was associated with higher frequency of children having subprotective antibody levels (Figure).

We examined whether accumulation of antibiotic courses in the first year of life had an association with subsequent vaccine-induced antibody levels and found that each antibiotic prescription was associated with a reduction in the median antibody level. For DTaP, each prescription was associated with 5.8% drop in antibody level to the vaccine components. For Hib the drop was 6.8%, IPV was 11.3%, and PCV was 10.4% – all statistically significant. To determine if booster vaccination influenced this association, a second analysis was performed using antibiotic prescriptions up to 15 months of age. We found each antibiotic prescription was associated with a reduction in median vaccine-induced antibody levels for DTaP by 18%, Hib by 21%, IPV by 19%, and PCV by 12% – all statistically significant.

Our study is the first in young children during the early age window where vaccine-induced immunity is established. Antibiotic use was associated with increased frequency of subprotective antibody levels for several vaccines used in children up to 2 years of age. The lower antibody levels could leave children vulnerable to vaccine preventable diseases. Perhaps outbreaks of vaccine-preventable diseases, such as pertussis, may be a consequence of multiple courses of antibiotics suppressing vaccine-induced immunity.

A goal of this study was to explore potential acute and long-term effects of antibiotic exposure on vaccine-induced antibody levels. Accumulated antibiotic courses up to booster immunization was associated with decreased vaccine antibody levels both before and after booster, suggesting that booster immunization was not sufficient to change the negative association with antibiotic exposure. The results were similar for all vaccines tested, suggesting that the specific vaccine formulation was not a factor.

The study has several limitations. The antibiotic prescription data and measurements of vaccine-induced antibody levels were recorded and measured prospectively; however, our analysis was done retrospectively. The group of study children was derived from my private practice in Rochester, N.Y., and may not be broadly representative of all children. The number of vaccine antibody measurements was limited by serum availability at some sampling time points in some children; and sometimes, the serum samples were collected far apart, which weakened our ability to perform longitudinal analyses. We did not collect stool samples from the children so we could not directly study the effect of antibiotic courses on the gut microbiome.

Our study adds new reasons to be cautious about overprescribing antibiotics on an individual child basis because an adverse effect extends to reduction in vaccine responses. This should be explained to parents requesting unnecessary antibiotics for colds and coughs. When antibiotics are necessary, the judicious choice of a narrow-spectrum antibiotic or a shorter duration of a broader spectrum antibiotic may reduce adverse effects on vaccine-induced immunity.

References

1. Valdez Y et al. Influence of the microbiota on vaccine effectiveness. Trends Immunol. 2014;35(11):526-37.

2. Lynn MA et al. Early-life antibiotic-driven dysbiosis leads to dysregulated vaccine immune responses in mice. Cell Host Microbe. 2018;23(5):653-60.e5.

3. Hagan T et al. Antibiotics-driven gut microbiome perturbation alters immunity to vaccines in humans. Cell. 2019;178(6):1313-28.e13.

4. Chapman T et al. Antibiotic use and vaccine antibody levels. Pediatrics. 2022;149(5);1-17. doi: 10.1542/peds.2021-052061.

Fat shaming doesn’t work. If it did, obesity as we know it wouldn’t exist because if the one thing society ensures isn’t lacking for people with obesity, it’s shame. We know that fat shaming doesn’t lead to weight loss and that it’s actually correlated with weight gain: More shame leads to more gain (Puhl and Suh; Sutin and Terracciano; Tomiyama et al).

Shaming and weight stigma have far more concerning associations than weight gain. People who report experiencing more weight stigma have an increased risk for depression, anxiety, low self-esteem, poor body image, substance abuse, suicidality, unhealthy eating behaviors, disordered eating, increased caloric intake, exercise avoidance, decreased exercise motivation potentially due to heightened cortisol reactivity, elevated C-reactive protein, and elevated blood pressure.

Meanwhile, people with obesity – likely in part owing to negative weight-biased experiences in health care – are reluctant to discuss weight with their health care providers and are less likely to seek care at all for any conditions. When care is sought, people with obesity are more likely to receive substandard treatment, including receiving fewer preventive health screenings, decreased health education, and decreased time spent in appointments.
 

Remember that obesity is not a conscious choice

A fact that is conveniently forgotten by those who are most prone to fat shaming is that obesity, like every chronic noncommunicable disease, isn’t a choice that is consciously made by patients.

And yes, though there are lifestyle means that might affect weight, there are lifestyle means that might affect all chronic diseases – yet obesity is the only one we seem to moralize about. It’s also worth noting that other chronic diseases’ lifestyle levers tend not to be governed by thousands of genes and dozens of hormones; those trying to “lifestyle” their way out of obesity are swimming against strong physiologic currents that influence our most seminally important survival drive: eating.

But forgetting about physiologic currents, there is also staggering privilege associated with intentional perpetual behavior change around food and fitness in the name of health.

Whereas medicine and the world are right and quick to embrace the fights against racism, sexism, and homophobia, the push to confront weight bias is far rarer, despite the fact that it’s been shown to be rampant among health care professionals.
 

Protecting the rights of people with obesity

Perhaps though, times are changing. Movements are popping up to protect the rights of people with obesity while combating hate.

Of note, Brazil seems to have embraced a campaign to fight gordofobia — the Portuguese term used to describe weight-based discrimination. For instance, laws are being passed to ensure appropriate seating is supplied in schools for children with obesity, an annual day was formalized to promote the rights of people with obesity, preferential seating is provided on subways for people with obesity, and fines have been levied against at least one comedian for making fat jokes on the grounds of the state’s duty to protect minorities.

We need to take this fight to medicine. Given the incredibly depressing prevalence of weight bias among trainees, medical schools and residency programs should ensure countering weight bias is not only part of the curriculum but that it’s explicitly examined. National medical licensing examinations should include weight bias as well.

Though we’re closer than ever before to widely effective treatment options for obesity, it’s likely to still be decades before pharmaceutical options to treat obesity are as effective, accepted, and encouraged as medications to treat hypertension, dyslipidemia, diabetes, and more are today.

If you’re curious about your own implicit weight biases, consider taking Harvard’s Implicit Association Test for Weight. You might also want to take a few moments and review the Strategies to Overcome and Prevent Obesity Alliances’ Weight Can’t Wait guide for advice on the management of obesity in primary care.

Treat patients with obesity the same as you would those with any chronic condition.

Also, consider your physical office space. Do you have chairs suitable for patients with obesity (wide base and with arms to help patients rise)? A scale that measures up to high weights that’s in a private location? Appropriately sized blood pressure cuffs?

If not, do you know who is deserving of shame?

Doctors who fat shame or who treat patients with obesity differently than they would any other patient with a chronic medical condition.

Examples include the family doctor who hadn’t checked my patient’s blood pressure in over a decade because he couldn’t be bothered buying an appropriately sized blood pressure cuff. Or the fertility doctor who told one of my patients that perhaps her weight reflected God’s will that she does not have children.

Finally, if reading this article about treating people with obesity the same as you would patients with other chronic, noncommunicable, lifestyle responsive diseases made you angry, there’s a great chance that you’re part of the problem.
 

Dr. Freedhoff, is associate professor of family medicine at the University of Ottawa and medical director of the Bariatric Medical Institute, a nonsurgical weight management center. He is one of Canada’s most outspoken obesity experts and the author of The Diet Fix: Why Diets Fail and How to Make Yours Work. He has disclosed the following: He served as a director, officer, partner, employee, adviser, consultant, or trustee for Bariatric Medical Institute and Constant Health; has received research grant from Novo Nordisk, and has publicly shared opinions via Weighty Matters and social media. A version of this article first appeared on Medscape.com.

Fat shaming doesn’t work. If it did, obesity as we know it wouldn’t exist because if the one thing society ensures isn’t lacking for people with obesity, it’s shame. We know that fat shaming doesn’t lead to weight loss and that it’s actually correlated with weight gain: More shame leads to more gain (Puhl and Suh; Sutin and Terracciano; Tomiyama et al).

Shaming and weight stigma have far more concerning associations than weight gain. People who report experiencing more weight stigma have an increased risk for depression, anxiety, low self-esteem, poor body image, substance abuse, suicidality, unhealthy eating behaviors, disordered eating, increased caloric intake, exercise avoidance, decreased exercise motivation potentially due to heightened cortisol reactivity, elevated C-reactive protein, and elevated blood pressure.

Meanwhile, people with obesity – likely in part owing to negative weight-biased experiences in health care – are reluctant to discuss weight with their health care providers and are less likely to seek care at all for any conditions. When care is sought, people with obesity are more likely to receive substandard treatment, including receiving fewer preventive health screenings, decreased health education, and decreased time spent in appointments.
 

Remember that obesity is not a conscious choice

A fact that is conveniently forgotten by those who are most prone to fat shaming is that obesity, like every chronic noncommunicable disease, isn’t a choice that is consciously made by patients.

And yes, though there are lifestyle means that might affect weight, there are lifestyle means that might affect all chronic diseases – yet obesity is the only one we seem to moralize about. It’s also worth noting that other chronic diseases’ lifestyle levers tend not to be governed by thousands of genes and dozens of hormones; those trying to “lifestyle” their way out of obesity are swimming against strong physiologic currents that influence our most seminally important survival drive: eating.

But forgetting about physiologic currents, there is also staggering privilege associated with intentional perpetual behavior change around food and fitness in the name of health.

Whereas medicine and the world are right and quick to embrace the fights against racism, sexism, and homophobia, the push to confront weight bias is far rarer, despite the fact that it’s been shown to be rampant among health care professionals.
 

Protecting the rights of people with obesity

Perhaps though, times are changing. Movements are popping up to protect the rights of people with obesity while combating hate.

Of note, Brazil seems to have embraced a campaign to fight gordofobia — the Portuguese term used to describe weight-based discrimination. For instance, laws are being passed to ensure appropriate seating is supplied in schools for children with obesity, an annual day was formalized to promote the rights of people with obesity, preferential seating is provided on subways for people with obesity, and fines have been levied against at least one comedian for making fat jokes on the grounds of the state’s duty to protect minorities.

We need to take this fight to medicine. Given the incredibly depressing prevalence of weight bias among trainees, medical schools and residency programs should ensure countering weight bias is not only part of the curriculum but that it’s explicitly examined. National medical licensing examinations should include weight bias as well.

Though we’re closer than ever before to widely effective treatment options for obesity, it’s likely to still be decades before pharmaceutical options to treat obesity are as effective, accepted, and encouraged as medications to treat hypertension, dyslipidemia, diabetes, and more are today.

If you’re curious about your own implicit weight biases, consider taking Harvard’s Implicit Association Test for Weight. You might also want to take a few moments and review the Strategies to Overcome and Prevent Obesity Alliances’ Weight Can’t Wait guide for advice on the management of obesity in primary care.

Treat patients with obesity the same as you would those with any chronic condition.

Also, consider your physical office space. Do you have chairs suitable for patients with obesity (wide base and with arms to help patients rise)? A scale that measures up to high weights that’s in a private location? Appropriately sized blood pressure cuffs?

If not, do you know who is deserving of shame?

Doctors who fat shame or who treat patients with obesity differently than they would any other patient with a chronic medical condition.

Examples include the family doctor who hadn’t checked my patient’s blood pressure in over a decade because he couldn’t be bothered buying an appropriately sized blood pressure cuff. Or the fertility doctor who told one of my patients that perhaps her weight reflected God’s will that she does not have children.

Finally, if reading this article about treating people with obesity the same as you would patients with other chronic, noncommunicable, lifestyle responsive diseases made you angry, there’s a great chance that you’re part of the problem.
 

Dr. Freedhoff, is associate professor of family medicine at the University of Ottawa and medical director of the Bariatric Medical Institute, a nonsurgical weight management center. He is one of Canada’s most outspoken obesity experts and the author of The Diet Fix: Why Diets Fail and How to Make Yours Work. He has disclosed the following: He served as a director, officer, partner, employee, adviser, consultant, or trustee for Bariatric Medical Institute and Constant Health; has received research grant from Novo Nordisk, and has publicly shared opinions via Weighty Matters and social media. A version of this article first appeared on Medscape.com.

Fat shaming doesn’t work. If it did, obesity as we know it wouldn’t exist because if the one thing society ensures isn’t lacking for people with obesity, it’s shame. We know that fat shaming doesn’t lead to weight loss and that it’s actually correlated with weight gain: More shame leads to more gain (Puhl and Suh; Sutin and Terracciano; Tomiyama et al).

Shaming and weight stigma have far more concerning associations than weight gain. People who report experiencing more weight stigma have an increased risk for depression, anxiety, low self-esteem, poor body image, substance abuse, suicidality, unhealthy eating behaviors, disordered eating, increased caloric intake, exercise avoidance, decreased exercise motivation potentially due to heightened cortisol reactivity, elevated C-reactive protein, and elevated blood pressure.

Meanwhile, people with obesity – likely in part owing to negative weight-biased experiences in health care – are reluctant to discuss weight with their health care providers and are less likely to seek care at all for any conditions. When care is sought, people with obesity are more likely to receive substandard treatment, including receiving fewer preventive health screenings, decreased health education, and decreased time spent in appointments.
 

Remember that obesity is not a conscious choice

A fact that is conveniently forgotten by those who are most prone to fat shaming is that obesity, like every chronic noncommunicable disease, isn’t a choice that is consciously made by patients.

And yes, though there are lifestyle means that might affect weight, there are lifestyle means that might affect all chronic diseases – yet obesity is the only one we seem to moralize about. It’s also worth noting that other chronic diseases’ lifestyle levers tend not to be governed by thousands of genes and dozens of hormones; those trying to “lifestyle” their way out of obesity are swimming against strong physiologic currents that influence our most seminally important survival drive: eating.

But forgetting about physiologic currents, there is also staggering privilege associated with intentional perpetual behavior change around food and fitness in the name of health.

Whereas medicine and the world are right and quick to embrace the fights against racism, sexism, and homophobia, the push to confront weight bias is far rarer, despite the fact that it’s been shown to be rampant among health care professionals.
 

Protecting the rights of people with obesity

Perhaps though, times are changing. Movements are popping up to protect the rights of people with obesity while combating hate.

Of note, Brazil seems to have embraced a campaign to fight gordofobia — the Portuguese term used to describe weight-based discrimination. For instance, laws are being passed to ensure appropriate seating is supplied in schools for children with obesity, an annual day was formalized to promote the rights of people with obesity, preferential seating is provided on subways for people with obesity, and fines have been levied against at least one comedian for making fat jokes on the grounds of the state’s duty to protect minorities.

We need to take this fight to medicine. Given the incredibly depressing prevalence of weight bias among trainees, medical schools and residency programs should ensure countering weight bias is not only part of the curriculum but that it’s explicitly examined. National medical licensing examinations should include weight bias as well.

Though we’re closer than ever before to widely effective treatment options for obesity, it’s likely to still be decades before pharmaceutical options to treat obesity are as effective, accepted, and encouraged as medications to treat hypertension, dyslipidemia, diabetes, and more are today.

If you’re curious about your own implicit weight biases, consider taking Harvard’s Implicit Association Test for Weight. You might also want to take a few moments and review the Strategies to Overcome and Prevent Obesity Alliances’ Weight Can’t Wait guide for advice on the management of obesity in primary care.

Treat patients with obesity the same as you would those with any chronic condition.

Also, consider your physical office space. Do you have chairs suitable for patients with obesity (wide base and with arms to help patients rise)? A scale that measures up to high weights that’s in a private location? Appropriately sized blood pressure cuffs?

If not, do you know who is deserving of shame?

Doctors who fat shame or who treat patients with obesity differently than they would any other patient with a chronic medical condition.

Examples include the family doctor who hadn’t checked my patient’s blood pressure in over a decade because he couldn’t be bothered buying an appropriately sized blood pressure cuff. Or the fertility doctor who told one of my patients that perhaps her weight reflected God’s will that she does not have children.

Finally, if reading this article about treating people with obesity the same as you would patients with other chronic, noncommunicable, lifestyle responsive diseases made you angry, there’s a great chance that you’re part of the problem.
 

Dr. Freedhoff, is associate professor of family medicine at the University of Ottawa and medical director of the Bariatric Medical Institute, a nonsurgical weight management center. He is one of Canada’s most outspoken obesity experts and the author of The Diet Fix: Why Diets Fail and How to Make Yours Work. He has disclosed the following: He served as a director, officer, partner, employee, adviser, consultant, or trustee for Bariatric Medical Institute and Constant Health; has received research grant from Novo Nordisk, and has publicly shared opinions via Weighty Matters and social media. A version of this article first appeared on Medscape.com.

Psychiatrists practice a field of medicine that relies on one’s clinical perspective to interpret observable behaviors originating from the brains of others. In this manner, psychiatry and photography are similar. And digital technology has changed them both.

In photography, there are many technical aspects for one to master when framing and capturing a shot. The length of exposure. The amount of light needed. The speed of the film, which is its sensitivity to light. The aperture that controls how much light falls on the film. The movement of the subject across the film during the exposure. Despite the fact that physical film has mostly yielded to electronic sensors over the past couple decades, these basic aspects of photography remain.

But perspective is the critical ingredient. This is what brings the greatest impact to photography. The composition, or the subject of the photograph and how its elements – foreground, background, shapes, patterns, texture, shadow, motion, leading lines, and focal points – are arranged. The most powerful way to improve the composition – more powerful than fancy camera bells and whistles – is to move. One step to the left or right, one step forward or back. Stand on your toes, or crouch to your knees. Pivot this way or that. A simple change in perspective dramatically changes the nature and the energy of the captured image.

While the field of medicine has similarly been impacted by the onset of digital technology, physicians’ perspectives about their work remain the key factor in the nature and the energy of what we do.

In fact, many physicians are changing what they actually do for a living. Pivoting their clinical perspectives. And applying those perspectives to other areas. The latest catalyst fueling these career pivots, these changes in perspectives, has been the incredible global impact of the tiny little coronavirus known as SARS-CoV-2. The COVID-19 pandemic that began two years ago has disrupted the entire planet. The virus has caused us all to change our perspective, to see our world differently, and our place in it.

The virus has exposed defects in our health care delivery system. And physicians have necessarily reacted, injecting changes in what they do and how they do it. Many of these changes rely on digital technology, building upon the groundwork laid over the past couple of decades to convert our paper processes into electronic processes, and our manual work flows into digital work flows. This groundwork is no small thing, as it relies on conventions and standards, such as DICOM, LOINC, AES, CDA, UMLS, FHIR, ICD, NDC, USCDI, and SNOMED-CT. Establishing, maintaining, and evolving health care standards requires organized groups of people to come together to share their diverse perspectives. This is but one of many places where physicians are using their unique clinical perspective to share what they see with others.

This column will focus on these professional pivots that physicians make when they take a step to the left or right to change their perspective and share their viewpoints in different settings with diverse groups of people. Some of these pivots are small, while others are career changing. But the theme that knits them together is about taking what one has learned while helping others achieve better health, and using that perspective to make a difference.

Dr. Daviss is chief medical officer for Optum Maryland and immediate past president of the Maryland-DC Society of Addiction Medicine, and former medical director and senior medical advisor at SAMHSA. He is coauthor of the 2011 book, Shrink Rap: Three Psychiatrists Explain Their Work. Psychiatrists and other physicians may share their own experience with pivots they have made with Dr. Daviss via email ([email protected]) or Twitter (@HITshrink). The opinions expressed are solely those of the author and do not necessarily reflect those of his employer or organizations with which he is associated.

Psychiatrists practice a field of medicine that relies on one’s clinical perspective to interpret observable behaviors originating from the brains of others. In this manner, psychiatry and photography are similar. And digital technology has changed them both.

In photography, there are many technical aspects for one to master when framing and capturing a shot. The length of exposure. The amount of light needed. The speed of the film, which is its sensitivity to light. The aperture that controls how much light falls on the film. The movement of the subject across the film during the exposure. Despite the fact that physical film has mostly yielded to electronic sensors over the past couple decades, these basic aspects of photography remain.

But perspective is the critical ingredient. This is what brings the greatest impact to photography. The composition, or the subject of the photograph and how its elements – foreground, background, shapes, patterns, texture, shadow, motion, leading lines, and focal points – are arranged. The most powerful way to improve the composition – more powerful than fancy camera bells and whistles – is to move. One step to the left or right, one step forward or back. Stand on your toes, or crouch to your knees. Pivot this way or that. A simple change in perspective dramatically changes the nature and the energy of the captured image.

While the field of medicine has similarly been impacted by the onset of digital technology, physicians’ perspectives about their work remain the key factor in the nature and the energy of what we do.

In fact, many physicians are changing what they actually do for a living. Pivoting their clinical perspectives. And applying those perspectives to other areas. The latest catalyst fueling these career pivots, these changes in perspectives, has been the incredible global impact of the tiny little coronavirus known as SARS-CoV-2. The COVID-19 pandemic that began two years ago has disrupted the entire planet. The virus has caused us all to change our perspective, to see our world differently, and our place in it.

The virus has exposed defects in our health care delivery system. And physicians have necessarily reacted, injecting changes in what they do and how they do it. Many of these changes rely on digital technology, building upon the groundwork laid over the past couple of decades to convert our paper processes into electronic processes, and our manual work flows into digital work flows. This groundwork is no small thing, as it relies on conventions and standards, such as DICOM, LOINC, AES, CDA, UMLS, FHIR, ICD, NDC, USCDI, and SNOMED-CT. Establishing, maintaining, and evolving health care standards requires organized groups of people to come together to share their diverse perspectives. This is but one of many places where physicians are using their unique clinical perspective to share what they see with others.

This column will focus on these professional pivots that physicians make when they take a step to the left or right to change their perspective and share their viewpoints in different settings with diverse groups of people. Some of these pivots are small, while others are career changing. But the theme that knits them together is about taking what one has learned while helping others achieve better health, and using that perspective to make a difference.

Dr. Daviss is chief medical officer for Optum Maryland and immediate past president of the Maryland-DC Society of Addiction Medicine, and former medical director and senior medical advisor at SAMHSA. He is coauthor of the 2011 book, Shrink Rap: Three Psychiatrists Explain Their Work. Psychiatrists and other physicians may share their own experience with pivots they have made with Dr. Daviss via email ([email protected]) or Twitter (@HITshrink). The opinions expressed are solely those of the author and do not necessarily reflect those of his employer or organizations with which he is associated.

Psychiatrists practice a field of medicine that relies on one’s clinical perspective to interpret observable behaviors originating from the brains of others. In this manner, psychiatry and photography are similar. And digital technology has changed them both.

In photography, there are many technical aspects for one to master when framing and capturing a shot. The length of exposure. The amount of light needed. The speed of the film, which is its sensitivity to light. The aperture that controls how much light falls on the film. The movement of the subject across the film during the exposure. Despite the fact that physical film has mostly yielded to electronic sensors over the past couple decades, these basic aspects of photography remain.

But perspective is the critical ingredient. This is what brings the greatest impact to photography. The composition, or the subject of the photograph and how its elements – foreground, background, shapes, patterns, texture, shadow, motion, leading lines, and focal points – are arranged. The most powerful way to improve the composition – more powerful than fancy camera bells and whistles – is to move. One step to the left or right, one step forward or back. Stand on your toes, or crouch to your knees. Pivot this way or that. A simple change in perspective dramatically changes the nature and the energy of the captured image.

While the field of medicine has similarly been impacted by the onset of digital technology, physicians’ perspectives about their work remain the key factor in the nature and the energy of what we do.

In fact, many physicians are changing what they actually do for a living. Pivoting their clinical perspectives. And applying those perspectives to other areas. The latest catalyst fueling these career pivots, these changes in perspectives, has been the incredible global impact of the tiny little coronavirus known as SARS-CoV-2. The COVID-19 pandemic that began two years ago has disrupted the entire planet. The virus has caused us all to change our perspective, to see our world differently, and our place in it.

The virus has exposed defects in our health care delivery system. And physicians have necessarily reacted, injecting changes in what they do and how they do it. Many of these changes rely on digital technology, building upon the groundwork laid over the past couple of decades to convert our paper processes into electronic processes, and our manual work flows into digital work flows. This groundwork is no small thing, as it relies on conventions and standards, such as DICOM, LOINC, AES, CDA, UMLS, FHIR, ICD, NDC, USCDI, and SNOMED-CT. Establishing, maintaining, and evolving health care standards requires organized groups of people to come together to share their diverse perspectives. This is but one of many places where physicians are using their unique clinical perspective to share what they see with others.

This column will focus on these professional pivots that physicians make when they take a step to the left or right to change their perspective and share their viewpoints in different settings with diverse groups of people. Some of these pivots are small, while others are career changing. But the theme that knits them together is about taking what one has learned while helping others achieve better health, and using that perspective to make a difference.

Dr. Daviss is chief medical officer for Optum Maryland and immediate past president of the Maryland-DC Society of Addiction Medicine, and former medical director and senior medical advisor at SAMHSA. He is coauthor of the 2011 book, Shrink Rap: Three Psychiatrists Explain Their Work. Psychiatrists and other physicians may share their own experience with pivots they have made with Dr. Daviss via email ([email protected]) or Twitter (@HITshrink). The opinions expressed are solely those of the author and do not necessarily reflect those of his employer or organizations with which he is associated.

On April 12, 2022, the U.S. Preventive Services Task Force released the draft of a recommendation statement titled Screening for Anxiety in Children and Adolescents. Based on their observation that 7.8% of children and adolescents have a current anxiety disorder and their analysis of the magnitude of the net benefit, the Task Force plans on recommending that children ages 8-18 years be screened for the condition. However, the group could not find evidence to support screening for children 7 years and younger.

Over more than 4 decades of general pediatric practice, it became obvious to me that anxiety was driving a high percentage of my office visits. Most often in young children it was parental anxiety that was prompting the phone call or office visit. In older childhood and adolescence it was patient anxiety that began to play a larger role.

Over the last 2 decades the level of anxiety in all age groups has seemed to increase. How large a role the events of Sept. 11, 2001, and other terrorist attacks were playing in this phenomenon is unclear to me. However, I suspect they were significant. More recently the pandemic and the failure of both political parties to forge a working arrangement have fueled even more anxiety in many demographic segments. It may be safe to say that everyone is anxious to one degree or another.

Broad-based anxiety in the general population and the incidence of anxiety disorders severe enough to disrupt a child’s life are certainly two different kettles of fish. However, the factors that have raised the level of anxiety across all age groups certainly hasn’t made things any easier for the child who has inherited or developed an anxiety disorder.

Glancing at the 600-page evidence synthesis that accompanies the task force’s report it is clear that they have taken their challenge seriously. However, I wonder whether looking at the 7-and-under age group with a different lens might have resulted in the inclusion of younger children in their recommendation.

I understand that to support their recommendations the U.S. Preventive Services Task Forces must rely on data from peer-reviewed studies that have looked at quantifiable outcomes. However, I suspect the task force would agree that its recommendations shouldn’t prevent the rest of us from using our own observations and intuition when deciding whether to selectively screen our younger patients for anxiety disorders.

Although it may not generate a measurable data point, providing the parents of a 5-year-old whose troubling behavior is in part the result of an anxiety disorder is invaluable. Do we need to screen all 5-year-olds? The task force says probably not given the current state of our knowledge and I agree. But, the fact that almost 8% of the pediatric population carries the diagnosis and my anecdotal observations suggest that as pediatricians we should be learning more about anxiety disorders and their wide variety of presentations. Then we should selectively screen more of our patients. In fact, I suspect we might help our patients and ourselves by questioning more parents about their own mental health histories even before we have any inkling that their child has a problem. While the degree to which anxiety disorders are inheritable and the exact mechanism is far from clear, I think this history might be a valuable piece of information to learn as early as the prenatal get-acquainted visit. A simple question to a new or expecting parent about what worries them most about becoming a parent would be a good opener. Your reassurance that you expect parents to be worried and welcome hearing about their concerns should be a step in building a strong foundation for a family-provider relationship.

Anxiety happens and unfortunately so do anxiety disorders. We need to be doing a better job of acknowledging and responding to these two realities.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

*This column was updated on 5/4/2022.

On April 12, 2022, the U.S. Preventive Services Task Force released the draft of a recommendation statement titled Screening for Anxiety in Children and Adolescents. Based on their observation that 7.8% of children and adolescents have a current anxiety disorder and their analysis of the magnitude of the net benefit, the Task Force plans on recommending that children ages 8-18 years be screened for the condition. However, the group could not find evidence to support screening for children 7 years and younger.

Over more than 4 decades of general pediatric practice, it became obvious to me that anxiety was driving a high percentage of my office visits. Most often in young children it was parental anxiety that was prompting the phone call or office visit. In older childhood and adolescence it was patient anxiety that began to play a larger role.

Over the last 2 decades the level of anxiety in all age groups has seemed to increase. How large a role the events of Sept. 11, 2001, and other terrorist attacks were playing in this phenomenon is unclear to me. However, I suspect they were significant. More recently the pandemic and the failure of both political parties to forge a working arrangement have fueled even more anxiety in many demographic segments. It may be safe to say that everyone is anxious to one degree or another.

Broad-based anxiety in the general population and the incidence of anxiety disorders severe enough to disrupt a child’s life are certainly two different kettles of fish. However, the factors that have raised the level of anxiety across all age groups certainly hasn’t made things any easier for the child who has inherited or developed an anxiety disorder.

Glancing at the 600-page evidence synthesis that accompanies the task force’s report it is clear that they have taken their challenge seriously. However, I wonder whether looking at the 7-and-under age group with a different lens might have resulted in the inclusion of younger children in their recommendation.

I understand that to support their recommendations the U.S. Preventive Services Task Forces must rely on data from peer-reviewed studies that have looked at quantifiable outcomes. However, I suspect the task force would agree that its recommendations shouldn’t prevent the rest of us from using our own observations and intuition when deciding whether to selectively screen our younger patients for anxiety disorders.

Although it may not generate a measurable data point, providing the parents of a 5-year-old whose troubling behavior is in part the result of an anxiety disorder is invaluable. Do we need to screen all 5-year-olds? The task force says probably not given the current state of our knowledge and I agree. But, the fact that almost 8% of the pediatric population carries the diagnosis and my anecdotal observations suggest that as pediatricians we should be learning more about anxiety disorders and their wide variety of presentations. Then we should selectively screen more of our patients. In fact, I suspect we might help our patients and ourselves by questioning more parents about their own mental health histories even before we have any inkling that their child has a problem. While the degree to which anxiety disorders are inheritable and the exact mechanism is far from clear, I think this history might be a valuable piece of information to learn as early as the prenatal get-acquainted visit. A simple question to a new or expecting parent about what worries them most about becoming a parent would be a good opener. Your reassurance that you expect parents to be worried and welcome hearing about their concerns should be a step in building a strong foundation for a family-provider relationship.

Anxiety happens and unfortunately so do anxiety disorders. We need to be doing a better job of acknowledging and responding to these two realities.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

*This column was updated on 5/4/2022.

On April 12, 2022, the U.S. Preventive Services Task Force released the draft of a recommendation statement titled Screening for Anxiety in Children and Adolescents. Based on their observation that 7.8% of children and adolescents have a current anxiety disorder and their analysis of the magnitude of the net benefit, the Task Force plans on recommending that children ages 8-18 years be screened for the condition. However, the group could not find evidence to support screening for children 7 years and younger.

Over more than 4 decades of general pediatric practice, it became obvious to me that anxiety was driving a high percentage of my office visits. Most often in young children it was parental anxiety that was prompting the phone call or office visit. In older childhood and adolescence it was patient anxiety that began to play a larger role.

Over the last 2 decades the level of anxiety in all age groups has seemed to increase. How large a role the events of Sept. 11, 2001, and other terrorist attacks were playing in this phenomenon is unclear to me. However, I suspect they were significant. More recently the pandemic and the failure of both political parties to forge a working arrangement have fueled even more anxiety in many demographic segments. It may be safe to say that everyone is anxious to one degree or another.

Broad-based anxiety in the general population and the incidence of anxiety disorders severe enough to disrupt a child’s life are certainly two different kettles of fish. However, the factors that have raised the level of anxiety across all age groups certainly hasn’t made things any easier for the child who has inherited or developed an anxiety disorder.

Glancing at the 600-page evidence synthesis that accompanies the task force’s report it is clear that they have taken their challenge seriously. However, I wonder whether looking at the 7-and-under age group with a different lens might have resulted in the inclusion of younger children in their recommendation.

I understand that to support their recommendations the U.S. Preventive Services Task Forces must rely on data from peer-reviewed studies that have looked at quantifiable outcomes. However, I suspect the task force would agree that its recommendations shouldn’t prevent the rest of us from using our own observations and intuition when deciding whether to selectively screen our younger patients for anxiety disorders.

Although it may not generate a measurable data point, providing the parents of a 5-year-old whose troubling behavior is in part the result of an anxiety disorder is invaluable. Do we need to screen all 5-year-olds? The task force says probably not given the current state of our knowledge and I agree. But, the fact that almost 8% of the pediatric population carries the diagnosis and my anecdotal observations suggest that as pediatricians we should be learning more about anxiety disorders and their wide variety of presentations. Then we should selectively screen more of our patients. In fact, I suspect we might help our patients and ourselves by questioning more parents about their own mental health histories even before we have any inkling that their child has a problem. While the degree to which anxiety disorders are inheritable and the exact mechanism is far from clear, I think this history might be a valuable piece of information to learn as early as the prenatal get-acquainted visit. A simple question to a new or expecting parent about what worries them most about becoming a parent would be a good opener. Your reassurance that you expect parents to be worried and welcome hearing about their concerns should be a step in building a strong foundation for a family-provider relationship.

Anxiety happens and unfortunately so do anxiety disorders. We need to be doing a better job of acknowledging and responding to these two realities.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

*This column was updated on 5/4/2022.

This video transcript has been edited for clarity.

Andrew N. Wilner, MD: Welcome to Medscape. I’m Dr Andrew Wilner, reporting from the American Epilepsy Society meeting.

Today, I have the pleasure of speaking with Dr. Chethan Rao, a child and adolescent neurology resident from the Mayo Clinic in Jacksonville, Fla. Dr. Rao has a particular interest in pediatric epilepsy. Welcome, Dr. Rao.

Chethan Rao, DO: Thank you, Dr. Wilner. It’s a pleasure to be here, and thanks for taking the time to highlight our work.

Dr. Wilner: You had a very interesting paper at the meeting that I wanted to talk about, focused on infantile spasms and smartphone video. Before we dive into the paper, tell us: What are infantile spasms, and why is it important to diagnose them early?

Dr. Rao: Infantile spasms, also known as epileptic spasms, are 1- to 2-second seizures, and they typically consist of sudden stiffening of the body with brief bending forward or backward of the arms, legs, and head. They usually happen around age 3-8 months, and they typically occur in clusters, most often after awakening from sleep.

The incidence is about 1 in 2,000-3,000 children. Many kids with spasms go on to develop seizures that are very difficult to treat, like Lennox-Gastaut epilepsy, and many go on to have developmental delays as well.

Dr. Wilner: Are these subtle? In other words, could a parent have a child like that and not really recognize that this is something abnormal? Or are they so dramatic that parents say: “We’re going to the emergency room?”

Dr. Rao: One of the problems that we encounter often is that in this age group of infants, they have benign sleep myoclonus; they have Sandifer syndrome related to reflux. Those can be very difficult mimics of spasms. They’re not the most clear-cut, but they look usually different enough from normal baby movements that they get parents to seek medical attention.

Dr. Wilner: You mentioned that the infantile spasms really are a type of epilepsy and symptomatic, usually, of some underlying neurologic condition. Why is it so important to diagnose them early?

Dr. Rao: Great question. Many studies have looked at developmental outcomes based on when spasms were diagnosed and treated, and all of them have replicated time over time that the earlier you get to treatment for the spasms, the better the outcomes are for seizure control and for development.

For this reason, infantile spasm is considered a neurologic urgency in our world. Like I said, accurate diagnosis is often complicated by these potential mimics. Prompt EEG is one of the most important things for confirmation of diagnosis.

Dr. Wilner: But to get that EEG, it has to get all the way to the neurologist, right? It’s not something they’re going to do in the ER. I saw a statistic: There are millions, if not billions, of smartphones out there. Where does the smartphone come in?

Dr. Rao: Absolutely. One of the things that we have on our side these days is that almost everyone has a smartphone at their disposal. One of the recent polls in 2021 showed that more than 95% of adults of childbearing age have smartphones with video access. As some other studies have shown in the adult world, we all really have an epilepsy monitoring unit minus the EEG in our own pockets.

It’s definitely a useful tool, as that first screening video can be used in adjunct to history and physical. There have been many of studies on the adult epilepsy side showing the predictive value of smartphone video for differentiating things like epileptic seizures and nonepileptic spells. What we wanted to do is use smartphone video to pin the diagnosis early of infantile spasms and get it treated as quickly as possible.

Dr. Wilner: I’m a fan. Every now and then, I do have a patient who brings in a video of some spell. I’m an adult neurologist. The patient had a spell, and you ask them – of course they don’t remember – and you ask the witness, who usually is not a trained observer. There have been one or two occasions where I thought: “Well, I don’t know if that was really a seizure.” Then they show me the video and it’s like, “Wow, that is definitely a convulsion.” A picture definitely can be worth a thousand words.

You studied this systematically for your poster. Tell me about what you did.

Dr. Rao: Since the poster, we’ve actually expanded the study, so I’ll give you the updated version. We looked at 101 infants retrospectively at two large children’s health care centers: Nemours Children’s, associated with Mayo Clinic in Jacksonville, Fla., and Texas Children’s Hospital in Houston. We narrowed it down to 80 patients whom we included. Of these, 43 had smartphone video capture when they first presented and 37 had no video when they first presented.

We found a 17-day difference by median in the time to diagnosis and treatment. In other words, the video group was diagnosed and treated 17 days by median, compared with the no-video group. Although 17 days may not sound like a big number, in this context it can make a huge difference. That’s been shown by one of these key studies in our field called the UK Infantile Spasms Study. The 2-week difference made about a 10-point difference on the developmental scale that they use – so pretty significant.

Dr. Wilner: Let me think about this for a minute. Was that because the parents brought the child in with their video and the doctor said, “Hey, that’s infantile spasms. Here’s your shot of ACTH [or whatever they’re using these days].” Or was it because the parents who were attentive enough to use video brought their kids in sooner?

Or was this the time from when they brought the child in to treatment? Is that the time you looked at? So it wasn’t just that these were more attentive parents and more likely to use the video – you’re looking at the time from presentation with or without video until treatment, is that right?

Dr. Rao: We looked to the time from the start of the spasms, as reported by the parents, to the time of diagnosis and then the start of spasms to the time of treatment. What you asked was a fantastic question. We wanted to know who these parents are who are taking videos versus the ones that are not.

We looked at the race/ethnicity data and socioeconomic status data. There were no significant differences between the video and nonvideo group. That would not explain the difference in our results here.

Dr. Wilner: Do you have plans to follow these approximately 40 children 5 years from now and see who’s riding a bicycle and who’s still stuck in the stroller? Is there going to be a difference?

Dr. Rao: Because time to diagnosis and time to treatment were our primary outcomes, long-term follow-up may not really help as much in this study. We did have a couple of other ideas for future studies. One that we wanted to look at was kids who have risk factors for developing spasms, such as trisomy 21, tuberous sclerosis, and congenital cortical malformations; those kids are at a much higher risk for developing spasms around 3-8 months of life.

In giving targeted counseling to those families about how they can use smartphone video to minimize the time to diagnosis and treatment, we think we may be able to learn more and maybe do that prospectively.

The other interesting idea is using artificial intelligence technology for spasm detection in some of these smartphone videos. They’re already using it for different seizure types. It could be an efficient first pass when we get a whole bunch of smartphone videos to determine which ones we need to pursue further steps – to see whether we need to get long-term EEG monitoring or not.

Dr. Wilner: As an epileptologist, I was going to say that we have smartphone EKG. All we need now is smartphone EEG, and then you’ll have all the information you need on day one. It may be a ways away.

As a bottom line, would it be fair to say that parents should not hesitate to take a video of any suspiciously abnormal behavior and bring it to their family doctor or pediatric neurologist?

Dr. Rao: Yes. I was happy to see the Tuberous Sclerosis Alliance put out a promotional video that had some steps for when parents see things that are suspicious for spasms, and they do recommend using smartphone video and promptly showing it to their doctors. I think the difference that we hope to provide in this study is that we can now quantify the effect of having that smartphone video when they first present.

My takeaway from this study that I would like to show is encouraging the use of smartphone video as an adjunct tool and for providers to ask for the videos, but also for these pediatric centers to develop an infrastructure – either a secure, monitored email address like we have at our center or a patient portal – where parents can submit video concerning for spasms.

Dr. Wilner: Save the trip to the doctor. Get that video out there first.

Dr. Rao: Especially in the pandemic world, right?

Dr. Wilner: Yes. I understand that you are a neurology resident. To wrap up, what’s the next step for you?

Dr. Rao: I’m finishing up my child neurology residency this year, and I’m moving out to Stanford for pediatric epilepsy fellowship. We’re preparing this project we’re talking about for submission soon, and we’re working on another project, which is a systematic review of genetic testing and the presurgical workup for pediatric drug-resistant focal epilepsy.

Dr. Wilner: Excellent. That’s pretty exciting. Good luck to you. I want to thank you very much for telling us about your research.

Dr. Rao: It was a pleasure speaking with you, and I look forward to the next time.

Dr. Wilner: I’m Dr Andrew Wilner, reporting for Medscape. Thanks for watching.

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

This video transcript has been edited for clarity.

Andrew N. Wilner, MD: Welcome to Medscape. I’m Dr Andrew Wilner, reporting from the American Epilepsy Society meeting.

Today, I have the pleasure of speaking with Dr. Chethan Rao, a child and adolescent neurology resident from the Mayo Clinic in Jacksonville, Fla. Dr. Rao has a particular interest in pediatric epilepsy. Welcome, Dr. Rao.

Chethan Rao, DO: Thank you, Dr. Wilner. It’s a pleasure to be here, and thanks for taking the time to highlight our work.

Dr. Wilner: You had a very interesting paper at the meeting that I wanted to talk about, focused on infantile spasms and smartphone video. Before we dive into the paper, tell us: What are infantile spasms, and why is it important to diagnose them early?

Dr. Rao: Infantile spasms, also known as epileptic spasms, are 1- to 2-second seizures, and they typically consist of sudden stiffening of the body with brief bending forward or backward of the arms, legs, and head. They usually happen around age 3-8 months, and they typically occur in clusters, most often after awakening from sleep.

The incidence is about 1 in 2,000-3,000 children. Many kids with spasms go on to develop seizures that are very difficult to treat, like Lennox-Gastaut epilepsy, and many go on to have developmental delays as well.

Dr. Wilner: Are these subtle? In other words, could a parent have a child like that and not really recognize that this is something abnormal? Or are they so dramatic that parents say: “We’re going to the emergency room?”

Dr. Rao: One of the problems that we encounter often is that in this age group of infants, they have benign sleep myoclonus; they have Sandifer syndrome related to reflux. Those can be very difficult mimics of spasms. They’re not the most clear-cut, but they look usually different enough from normal baby movements that they get parents to seek medical attention.

Dr. Wilner: You mentioned that the infantile spasms really are a type of epilepsy and symptomatic, usually, of some underlying neurologic condition. Why is it so important to diagnose them early?

Dr. Rao: Great question. Many studies have looked at developmental outcomes based on when spasms were diagnosed and treated, and all of them have replicated time over time that the earlier you get to treatment for the spasms, the better the outcomes are for seizure control and for development.

For this reason, infantile spasm is considered a neurologic urgency in our world. Like I said, accurate diagnosis is often complicated by these potential mimics. Prompt EEG is one of the most important things for confirmation of diagnosis.

Dr. Wilner: But to get that EEG, it has to get all the way to the neurologist, right? It’s not something they’re going to do in the ER. I saw a statistic: There are millions, if not billions, of smartphones out there. Where does the smartphone come in?

Dr. Rao: Absolutely. One of the things that we have on our side these days is that almost everyone has a smartphone at their disposal. One of the recent polls in 2021 showed that more than 95% of adults of childbearing age have smartphones with video access. As some other studies have shown in the adult world, we all really have an epilepsy monitoring unit minus the EEG in our own pockets.

It’s definitely a useful tool, as that first screening video can be used in adjunct to history and physical. There have been many of studies on the adult epilepsy side showing the predictive value of smartphone video for differentiating things like epileptic seizures and nonepileptic spells. What we wanted to do is use smartphone video to pin the diagnosis early of infantile spasms and get it treated as quickly as possible.

Dr. Wilner: I’m a fan. Every now and then, I do have a patient who brings in a video of some spell. I’m an adult neurologist. The patient had a spell, and you ask them – of course they don’t remember – and you ask the witness, who usually is not a trained observer. There have been one or two occasions where I thought: “Well, I don’t know if that was really a seizure.” Then they show me the video and it’s like, “Wow, that is definitely a convulsion.” A picture definitely can be worth a thousand words.

You studied this systematically for your poster. Tell me about what you did.

Dr. Rao: Since the poster, we’ve actually expanded the study, so I’ll give you the updated version. We looked at 101 infants retrospectively at two large children’s health care centers: Nemours Children’s, associated with Mayo Clinic in Jacksonville, Fla., and Texas Children’s Hospital in Houston. We narrowed it down to 80 patients whom we included. Of these, 43 had smartphone video capture when they first presented and 37 had no video when they first presented.

We found a 17-day difference by median in the time to diagnosis and treatment. In other words, the video group was diagnosed and treated 17 days by median, compared with the no-video group. Although 17 days may not sound like a big number, in this context it can make a huge difference. That’s been shown by one of these key studies in our field called the UK Infantile Spasms Study. The 2-week difference made about a 10-point difference on the developmental scale that they use – so pretty significant.

Dr. Wilner: Let me think about this for a minute. Was that because the parents brought the child in with their video and the doctor said, “Hey, that’s infantile spasms. Here’s your shot of ACTH [or whatever they’re using these days].” Or was it because the parents who were attentive enough to use video brought their kids in sooner?

Or was this the time from when they brought the child in to treatment? Is that the time you looked at? So it wasn’t just that these were more attentive parents and more likely to use the video – you’re looking at the time from presentation with or without video until treatment, is that right?

Dr. Rao: We looked to the time from the start of the spasms, as reported by the parents, to the time of diagnosis and then the start of spasms to the time of treatment. What you asked was a fantastic question. We wanted to know who these parents are who are taking videos versus the ones that are not.

We looked at the race/ethnicity data and socioeconomic status data. There were no significant differences between the video and nonvideo group. That would not explain the difference in our results here.

Dr. Wilner: Do you have plans to follow these approximately 40 children 5 years from now and see who’s riding a bicycle and who’s still stuck in the stroller? Is there going to be a difference?

Dr. Rao: Because time to diagnosis and time to treatment were our primary outcomes, long-term follow-up may not really help as much in this study. We did have a couple of other ideas for future studies. One that we wanted to look at was kids who have risk factors for developing spasms, such as trisomy 21, tuberous sclerosis, and congenital cortical malformations; those kids are at a much higher risk for developing spasms around 3-8 months of life.

In giving targeted counseling to those families about how they can use smartphone video to minimize the time to diagnosis and treatment, we think we may be able to learn more and maybe do that prospectively.

The other interesting idea is using artificial intelligence technology for spasm detection in some of these smartphone videos. They’re already using it for different seizure types. It could be an efficient first pass when we get a whole bunch of smartphone videos to determine which ones we need to pursue further steps – to see whether we need to get long-term EEG monitoring or not.

Dr. Wilner: As an epileptologist, I was going to say that we have smartphone EKG. All we need now is smartphone EEG, and then you’ll have all the information you need on day one. It may be a ways away.

As a bottom line, would it be fair to say that parents should not hesitate to take a video of any suspiciously abnormal behavior and bring it to their family doctor or pediatric neurologist?

Dr. Rao: Yes. I was happy to see the Tuberous Sclerosis Alliance put out a promotional video that had some steps for when parents see things that are suspicious for spasms, and they do recommend using smartphone video and promptly showing it to their doctors. I think the difference that we hope to provide in this study is that we can now quantify the effect of having that smartphone video when they first present.

My takeaway from this study that I would like to show is encouraging the use of smartphone video as an adjunct tool and for providers to ask for the videos, but also for these pediatric centers to develop an infrastructure – either a secure, monitored email address like we have at our center or a patient portal – where parents can submit video concerning for spasms.

Dr. Wilner: Save the trip to the doctor. Get that video out there first.

Dr. Rao: Especially in the pandemic world, right?

Dr. Wilner: Yes. I understand that you are a neurology resident. To wrap up, what’s the next step for you?

Dr. Rao: I’m finishing up my child neurology residency this year, and I’m moving out to Stanford for pediatric epilepsy fellowship. We’re preparing this project we’re talking about for submission soon, and we’re working on another project, which is a systematic review of genetic testing and the presurgical workup for pediatric drug-resistant focal epilepsy.

Dr. Wilner: Excellent. That’s pretty exciting. Good luck to you. I want to thank you very much for telling us about your research.

Dr. Rao: It was a pleasure speaking with you, and I look forward to the next time.

Dr. Wilner: I’m Dr Andrew Wilner, reporting for Medscape. Thanks for watching.

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

This video transcript has been edited for clarity.

Andrew N. Wilner, MD: Welcome to Medscape. I’m Dr Andrew Wilner, reporting from the American Epilepsy Society meeting.

Today, I have the pleasure of speaking with Dr. Chethan Rao, a child and adolescent neurology resident from the Mayo Clinic in Jacksonville, Fla. Dr. Rao has a particular interest in pediatric epilepsy. Welcome, Dr. Rao.

Chethan Rao, DO: Thank you, Dr. Wilner. It’s a pleasure to be here, and thanks for taking the time to highlight our work.

Dr. Wilner: You had a very interesting paper at the meeting that I wanted to talk about, focused on infantile spasms and smartphone video. Before we dive into the paper, tell us: What are infantile spasms, and why is it important to diagnose them early?

Dr. Rao: Infantile spasms, also known as epileptic spasms, are 1- to 2-second seizures, and they typically consist of sudden stiffening of the body with brief bending forward or backward of the arms, legs, and head. They usually happen around age 3-8 months, and they typically occur in clusters, most often after awakening from sleep.

The incidence is about 1 in 2,000-3,000 children. Many kids with spasms go on to develop seizures that are very difficult to treat, like Lennox-Gastaut epilepsy, and many go on to have developmental delays as well.

Dr. Wilner: Are these subtle? In other words, could a parent have a child like that and not really recognize that this is something abnormal? Or are they so dramatic that parents say: “We’re going to the emergency room?”

Dr. Rao: One of the problems that we encounter often is that in this age group of infants, they have benign sleep myoclonus; they have Sandifer syndrome related to reflux. Those can be very difficult mimics of spasms. They’re not the most clear-cut, but they look usually different enough from normal baby movements that they get parents to seek medical attention.

Dr. Wilner: You mentioned that the infantile spasms really are a type of epilepsy and symptomatic, usually, of some underlying neurologic condition. Why is it so important to diagnose them early?

Dr. Rao: Great question. Many studies have looked at developmental outcomes based on when spasms were diagnosed and treated, and all of them have replicated time over time that the earlier you get to treatment for the spasms, the better the outcomes are for seizure control and for development.

For this reason, infantile spasm is considered a neurologic urgency in our world. Like I said, accurate diagnosis is often complicated by these potential mimics. Prompt EEG is one of the most important things for confirmation of diagnosis.

Dr. Wilner: But to get that EEG, it has to get all the way to the neurologist, right? It’s not something they’re going to do in the ER. I saw a statistic: There are millions, if not billions, of smartphones out there. Where does the smartphone come in?

Dr. Rao: Absolutely. One of the things that we have on our side these days is that almost everyone has a smartphone at their disposal. One of the recent polls in 2021 showed that more than 95% of adults of childbearing age have smartphones with video access. As some other studies have shown in the adult world, we all really have an epilepsy monitoring unit minus the EEG in our own pockets.

It’s definitely a useful tool, as that first screening video can be used in adjunct to history and physical. There have been many of studies on the adult epilepsy side showing the predictive value of smartphone video for differentiating things like epileptic seizures and nonepileptic spells. What we wanted to do is use smartphone video to pin the diagnosis early of infantile spasms and get it treated as quickly as possible.

Dr. Wilner: I’m a fan. Every now and then, I do have a patient who brings in a video of some spell. I’m an adult neurologist. The patient had a spell, and you ask them – of course they don’t remember – and you ask the witness, who usually is not a trained observer. There have been one or two occasions where I thought: “Well, I don’t know if that was really a seizure.” Then they show me the video and it’s like, “Wow, that is definitely a convulsion.” A picture definitely can be worth a thousand words.

You studied this systematically for your poster. Tell me about what you did.

Dr. Rao: Since the poster, we’ve actually expanded the study, so I’ll give you the updated version. We looked at 101 infants retrospectively at two large children’s health care centers: Nemours Children’s, associated with Mayo Clinic in Jacksonville, Fla., and Texas Children’s Hospital in Houston. We narrowed it down to 80 patients whom we included. Of these, 43 had smartphone video capture when they first presented and 37 had no video when they first presented.

We found a 17-day difference by median in the time to diagnosis and treatment. In other words, the video group was diagnosed and treated 17 days by median, compared with the no-video group. Although 17 days may not sound like a big number, in this context it can make a huge difference. That’s been shown by one of these key studies in our field called the UK Infantile Spasms Study. The 2-week difference made about a 10-point difference on the developmental scale that they use – so pretty significant.

Dr. Wilner: Let me think about this for a minute. Was that because the parents brought the child in with their video and the doctor said, “Hey, that’s infantile spasms. Here’s your shot of ACTH [or whatever they’re using these days].” Or was it because the parents who were attentive enough to use video brought their kids in sooner?

Or was this the time from when they brought the child in to treatment? Is that the time you looked at? So it wasn’t just that these were more attentive parents and more likely to use the video – you’re looking at the time from presentation with or without video until treatment, is that right?

Dr. Rao: We looked to the time from the start of the spasms, as reported by the parents, to the time of diagnosis and then the start of spasms to the time of treatment. What you asked was a fantastic question. We wanted to know who these parents are who are taking videos versus the ones that are not.

We looked at the race/ethnicity data and socioeconomic status data. There were no significant differences between the video and nonvideo group. That would not explain the difference in our results here.

Dr. Wilner: Do you have plans to follow these approximately 40 children 5 years from now and see who’s riding a bicycle and who’s still stuck in the stroller? Is there going to be a difference?

Dr. Rao: Because time to diagnosis and time to treatment were our primary outcomes, long-term follow-up may not really help as much in this study. We did have a couple of other ideas for future studies. One that we wanted to look at was kids who have risk factors for developing spasms, such as trisomy 21, tuberous sclerosis, and congenital cortical malformations; those kids are at a much higher risk for developing spasms around 3-8 months of life.

In giving targeted counseling to those families about how they can use smartphone video to minimize the time to diagnosis and treatment, we think we may be able to learn more and maybe do that prospectively.

The other interesting idea is using artificial intelligence technology for spasm detection in some of these smartphone videos. They’re already using it for different seizure types. It could be an efficient first pass when we get a whole bunch of smartphone videos to determine which ones we need to pursue further steps – to see whether we need to get long-term EEG monitoring or not.

Dr. Wilner: As an epileptologist, I was going to say that we have smartphone EKG. All we need now is smartphone EEG, and then you’ll have all the information you need on day one. It may be a ways away.

As a bottom line, would it be fair to say that parents should not hesitate to take a video of any suspiciously abnormal behavior and bring it to their family doctor or pediatric neurologist?

Dr. Rao: Yes. I was happy to see the Tuberous Sclerosis Alliance put out a promotional video that had some steps for when parents see things that are suspicious for spasms, and they do recommend using smartphone video and promptly showing it to their doctors. I think the difference that we hope to provide in this study is that we can now quantify the effect of having that smartphone video when they first present.

My takeaway from this study that I would like to show is encouraging the use of smartphone video as an adjunct tool and for providers to ask for the videos, but also for these pediatric centers to develop an infrastructure – either a secure, monitored email address like we have at our center or a patient portal – where parents can submit video concerning for spasms.

Dr. Wilner: Save the trip to the doctor. Get that video out there first.

Dr. Rao: Especially in the pandemic world, right?

Dr. Wilner: Yes. I understand that you are a neurology resident. To wrap up, what’s the next step for you?

Dr. Rao: I’m finishing up my child neurology residency this year, and I’m moving out to Stanford for pediatric epilepsy fellowship. We’re preparing this project we’re talking about for submission soon, and we’re working on another project, which is a systematic review of genetic testing and the presurgical workup for pediatric drug-resistant focal epilepsy.

Dr. Wilner: Excellent. That’s pretty exciting. Good luck to you. I want to thank you very much for telling us about your research.

Dr. Rao: It was a pleasure speaking with you, and I look forward to the next time.

Dr. Wilner: I’m Dr Andrew Wilner, reporting for Medscape. Thanks for watching.

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

In 2021, the Food and Drug Administration approved 50 new drugs, but 24 will not be described here because they would probably not be used in pregnancy. The 24 are Aduhelm (aducanumab) to treat Alzheimer’s disease; Azstarys (serdexmethylphenidate and dexmethylphenidate), a combination CNS stimulant indicated for the treatment of ADHD; Cabenuva (cabotegravir and rilpivirine) to treat HIV; Voxzogo (vosoritide) for children with achondroplasia and open epiphyses; Qelbree (viloxazine) used in children aged 6-17 years to treat ADHD; and Pylarify (piflufolastat) for prostate cancer. Other anticancer drugs that will not be covered are Cosela (trilaciclib), Cytalux (pafolacianine), Exkivity (mobocertinib); Fotivda (tivozanib), Jemperli (dostarlimab-gxly), Lumakras (sotorasib), Pepaxto (melphalan flufenamide), Rybrevant (amivantamab-vmjw), Rylaze (asparaginase erwinia chrysanthemi), Scemblix (asciminib), Tepmetko (tepotinib), Tivdak (tisotumab vedotin-tftv), Truseltiq (infigratinib), Ukoniq (umbralisib), and Zynlonta (loncastuximab tesirine-lpyl).

Skytrofa (lonapegsomatropin-tcgd) will not be described below because it is indicated to treat short stature and is unlikely to be used in pregnancy. Nextstellis (drospirenone and estetrol) is used to prevent pregnancy.

Typically, for new drugs there will be no published reports describing their use in pregnant women. That information will come much later. In the sections below, the indications, effects on pregnant animals, and the potential for harm of a fetus/embryo are described. However, the relevance of animal data to human pregnancies is not great.

Adbry (tralokinumab) (molecular weight [MW], 147 kilodaltons), is indicated for the treatment of moderate to severe atopic dermatitis in adult patients whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable. The drug did not harm fetal monkeys at doses that were 10 times the maximum recommended human dose.

Besremi (ropeginterferon alfa-2b-njft) (MW, 60 kDa) is an interferon alfa-2b indicated for the treatment of adults with polycythemia vera. It is given by subcutaneous injection every 2 weeks. Animal studies assessing reproductive toxicity have not been conducted. The manufacturer states that the drug may cause fetal harm and should be assumed to have abortifacient potential.

Brexafemme (ibrexafungerp) (MW, 922) is indicated for the treatment of vulvovaginal candidiasis. The drug was teratogenic in pregnant rabbits but not in pregnant rats. The manufacturer recommends females with reproductive potential should use effective contraception during treatment and for 4 days after the final dose.

Bylvay (odevixibat) (MW unknown) is indicated for the treatment of pruritus in patients aged 3 months and older. There are no human data regarding its use in pregnant women. The drug was teratogenic in pregnant rabbits. Although there are no data, the drug has low absorption following oral administration and breastfeeding is not expected to result in exposure of the infant.

Empaveli (pegcetacoplan) (MW, 44 kDa) is used to treat paroxysmal nocturnal hemoglobinuria. When the drug was given to pregnant cynomolgus monkeys there was an increase in abortions and stillbirths.

Evkeeza (evinacumab-dgnb) (MW, 146k) is used to treat homozygous familial hypercholesterolemia. The drug was teratogenic in rabbits but not rats.

Fexinidazole (MW not specified) is indicated to treat human African trypanosomiasis caused by the parasite Trypanosoma brucei gambiense. Additional information not available.

Kerendia (finerenone) (MW, 378), is indicated to reduce the risk of kidney and heart complications in chronic kidney disease associated with type 2 diabetes. The drug was teratogenic in rats.

Korsuva (difelikefalin) (MW, 679) is a kappa opioid–receptor agonist indicated for the treatment of moderate to severe pruritus associated with chronic kidney disease in adults undergoing hemodialysis. No adverse effects were observed in pregnant rats and rabbits. The limited human data on use of Korsuva in pregnant women are not sufficient to evaluate a drug associated risk for major birth defects or miscarriage.

Leqvio (inclisiran) (MW, 17,285) is indicated to treat heterozygous familial hypercholesterolemia or clinical atherosclerotic cardiovascular disease as an add-on therapy. The drug was not teratogenic in rats and rabbits.

Livmarli (maralixibat) (MW, 710) is indicated for the treatment of cholestatic pruritus associated with Alagille syndrome. Because systemic absorption is low, the recommended clinical dose is not expected to result in measurable fetal exposure. No effects on fetal rats were observed.

Livtencity (maribavir) (MW, 376) is used to treat posttransplant cytomegalovirus infection that has not responded to other treatment. Embryo/fetal survival was reduced in rats but not in rabbits at doses less then the human dose.

Lupkynis (voclosporin) (MW, 1,215) is used to treat nephritis. Avoid use of Lupkynis in pregnant women because of the alcohol content of the drug formulation. The drug was embryocidal and feticidal in rats and rabbits but with no treatment-related fetal malformations or variations.

Lybalvi (olanzapine and samidorphan) (MW, 312 and 505) is a combination drug used to treat schizophrenia and bipolar disorder. It was fetal toxic in pregnant rats and rabbits but with no evidence of malformations. There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to atypical antipsychotics, including this drug, during pregnancy. Health care providers are encouraged to register patients by contacting the National Pregnancy Registry for Atypical Antipsychotics at 1-866-961-2388 or visit the Reproductive Psychiatry Resource and Information Center of the MGH Center for Women’s Mental Health.

Nexviazyme (avalglucosidase alfa-ngpt) (MW, 124k) is a hydrolytic lysosomal glycogen-specific enzyme indicated for the treatment of patients aged 1 year and older with late-onset Pompe disease. The drug was not teratogenic in mice and rabbits.

Nulibry (fosdenopterin) (MW, 480) is used to reduce the risk of mortality in molybdenum cofactor deficiency type A. Studies have not been conducted in pregnant animals.

Ponvory (ponesimod) (MW, 461) is used to treat relapsing forms of multiple sclerosis. The drug caused severe adverse effects in pregnant rats and rabbits.

Qulipta (atogepant) (MW, 604) is indicated to prevent episodic migraines. It is embryo/fetal toxic in rats and rabbits.

Saphnelo (anifrolumab-fnia) (MW, 148k) is used to treat moderate to severe systemic lupus erythematosus along with standard therapy. In pregnant cynomolgus monkeys, there was no evidence of embryotoxicity or fetal malformations with exposures up to approximately 28 times the exposure at the maximum recommended human dose.

Tavneos (avacopan) (MW, 582) is indicated to treat severe active antineutrophil cytoplasmic autoantibody–associated vasculitis in combination with standard therapy including glucocorticoids. There appears to be an increased risk for hepatotoxicity. The drug caused no defects in hamsters and rabbits, but in rabbits there was an increase in abortions.

Tezspire (tezepelumab-ekko) (MW, 147k) is indicated to treat severe asthma as an add-on maintenance therapy. No adverse fetal effects were observed in pregnant cynomolgus monkeys.

Verquvo (vericiguat) (MW, 426) is used to mitigate the risk of cardiovascular death and hospitalization for chronic heart failure. The drug was teratogenic in pregnant rabbits but not rats.

Vyvgart (efgartigimod alfa-fcab) (MW, 54k) is indicated to treat generalized myasthenia gravis. The drug did not cause birth defects in rats and rabbits.

Welireg (belzutifan) (MW, 383) is used to treat von Hippel–Lindau disease. In pregnant rats, the drug caused embryo-fetal lethality, reduced fetal body weight, and caused fetal skeletal malformations at maternal exposures of at least 0.2 times the human exposures.

Zegalogue (dasiglucagon) (MW, 3,382) is used to treat severe hypoglycemia. The drug did not cause birth defects in pregnant rats and rabbits.
 

Breastfeeding

It is not known if the above drugs will be in breast milk, but the safest course for an infant is to not breast feed if the mother is taking any of the above drugs.

Mr. Briggs is clinical professor of pharmacy at the University of California, San Francisco, and adjunct professor of pharmacy at the University of Southern California, Los Angeles, as well as at Washington State University, Spokane. Mr. Briggs said he had no relevant financial disclosures. Email him at [email protected].

In 2021, the Food and Drug Administration approved 50 new drugs, but 24 will not be described here because they would probably not be used in pregnancy. The 24 are Aduhelm (aducanumab) to treat Alzheimer’s disease; Azstarys (serdexmethylphenidate and dexmethylphenidate), a combination CNS stimulant indicated for the treatment of ADHD; Cabenuva (cabotegravir and rilpivirine) to treat HIV; Voxzogo (vosoritide) for children with achondroplasia and open epiphyses; Qelbree (viloxazine) used in children aged 6-17 years to treat ADHD; and Pylarify (piflufolastat) for prostate cancer. Other anticancer drugs that will not be covered are Cosela (trilaciclib), Cytalux (pafolacianine), Exkivity (mobocertinib); Fotivda (tivozanib), Jemperli (dostarlimab-gxly), Lumakras (sotorasib), Pepaxto (melphalan flufenamide), Rybrevant (amivantamab-vmjw), Rylaze (asparaginase erwinia chrysanthemi), Scemblix (asciminib), Tepmetko (tepotinib), Tivdak (tisotumab vedotin-tftv), Truseltiq (infigratinib), Ukoniq (umbralisib), and Zynlonta (loncastuximab tesirine-lpyl).

Skytrofa (lonapegsomatropin-tcgd) will not be described below because it is indicated to treat short stature and is unlikely to be used in pregnancy. Nextstellis (drospirenone and estetrol) is used to prevent pregnancy.

Typically, for new drugs there will be no published reports describing their use in pregnant women. That information will come much later. In the sections below, the indications, effects on pregnant animals, and the potential for harm of a fetus/embryo are described. However, the relevance of animal data to human pregnancies is not great.

Adbry (tralokinumab) (molecular weight [MW], 147 kilodaltons), is indicated for the treatment of moderate to severe atopic dermatitis in adult patients whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable. The drug did not harm fetal monkeys at doses that were 10 times the maximum recommended human dose.

Besremi (ropeginterferon alfa-2b-njft) (MW, 60 kDa) is an interferon alfa-2b indicated for the treatment of adults with polycythemia vera. It is given by subcutaneous injection every 2 weeks. Animal studies assessing reproductive toxicity have not been conducted. The manufacturer states that the drug may cause fetal harm and should be assumed to have abortifacient potential.

Brexafemme (ibrexafungerp) (MW, 922) is indicated for the treatment of vulvovaginal candidiasis. The drug was teratogenic in pregnant rabbits but not in pregnant rats. The manufacturer recommends females with reproductive potential should use effective contraception during treatment and for 4 days after the final dose.

Bylvay (odevixibat) (MW unknown) is indicated for the treatment of pruritus in patients aged 3 months and older. There are no human data regarding its use in pregnant women. The drug was teratogenic in pregnant rabbits. Although there are no data, the drug has low absorption following oral administration and breastfeeding is not expected to result in exposure of the infant.

Empaveli (pegcetacoplan) (MW, 44 kDa) is used to treat paroxysmal nocturnal hemoglobinuria. When the drug was given to pregnant cynomolgus monkeys there was an increase in abortions and stillbirths.

Evkeeza (evinacumab-dgnb) (MW, 146k) is used to treat homozygous familial hypercholesterolemia. The drug was teratogenic in rabbits but not rats.

Fexinidazole (MW not specified) is indicated to treat human African trypanosomiasis caused by the parasite Trypanosoma brucei gambiense. Additional information not available.

Kerendia (finerenone) (MW, 378), is indicated to reduce the risk of kidney and heart complications in chronic kidney disease associated with type 2 diabetes. The drug was teratogenic in rats.

Korsuva (difelikefalin) (MW, 679) is a kappa opioid–receptor agonist indicated for the treatment of moderate to severe pruritus associated with chronic kidney disease in adults undergoing hemodialysis. No adverse effects were observed in pregnant rats and rabbits. The limited human data on use of Korsuva in pregnant women are not sufficient to evaluate a drug associated risk for major birth defects or miscarriage.

Leqvio (inclisiran) (MW, 17,285) is indicated to treat heterozygous familial hypercholesterolemia or clinical atherosclerotic cardiovascular disease as an add-on therapy. The drug was not teratogenic in rats and rabbits.

Livmarli (maralixibat) (MW, 710) is indicated for the treatment of cholestatic pruritus associated with Alagille syndrome. Because systemic absorption is low, the recommended clinical dose is not expected to result in measurable fetal exposure. No effects on fetal rats were observed.

Livtencity (maribavir) (MW, 376) is used to treat posttransplant cytomegalovirus infection that has not responded to other treatment. Embryo/fetal survival was reduced in rats but not in rabbits at doses less then the human dose.

Lupkynis (voclosporin) (MW, 1,215) is used to treat nephritis. Avoid use of Lupkynis in pregnant women because of the alcohol content of the drug formulation. The drug was embryocidal and feticidal in rats and rabbits but with no treatment-related fetal malformations or variations.

Lybalvi (olanzapine and samidorphan) (MW, 312 and 505) is a combination drug used to treat schizophrenia and bipolar disorder. It was fetal toxic in pregnant rats and rabbits but with no evidence of malformations. There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to atypical antipsychotics, including this drug, during pregnancy. Health care providers are encouraged to register patients by contacting the National Pregnancy Registry for Atypical Antipsychotics at 1-866-961-2388 or visit the Reproductive Psychiatry Resource and Information Center of the MGH Center for Women’s Mental Health.

Nexviazyme (avalglucosidase alfa-ngpt) (MW, 124k) is a hydrolytic lysosomal glycogen-specific enzyme indicated for the treatment of patients aged 1 year and older with late-onset Pompe disease. The drug was not teratogenic in mice and rabbits.

Nulibry (fosdenopterin) (MW, 480) is used to reduce the risk of mortality in molybdenum cofactor deficiency type A. Studies have not been conducted in pregnant animals.

Ponvory (ponesimod) (MW, 461) is used to treat relapsing forms of multiple sclerosis. The drug caused severe adverse effects in pregnant rats and rabbits.

Qulipta (atogepant) (MW, 604) is indicated to prevent episodic migraines. It is embryo/fetal toxic in rats and rabbits.

Saphnelo (anifrolumab-fnia) (MW, 148k) is used to treat moderate to severe systemic lupus erythematosus along with standard therapy. In pregnant cynomolgus monkeys, there was no evidence of embryotoxicity or fetal malformations with exposures up to approximately 28 times the exposure at the maximum recommended human dose.

Tavneos (avacopan) (MW, 582) is indicated to treat severe active antineutrophil cytoplasmic autoantibody–associated vasculitis in combination with standard therapy including glucocorticoids. There appears to be an increased risk for hepatotoxicity. The drug caused no defects in hamsters and rabbits, but in rabbits there was an increase in abortions.

Tezspire (tezepelumab-ekko) (MW, 147k) is indicated to treat severe asthma as an add-on maintenance therapy. No adverse fetal effects were observed in pregnant cynomolgus monkeys.

Verquvo (vericiguat) (MW, 426) is used to mitigate the risk of cardiovascular death and hospitalization for chronic heart failure. The drug was teratogenic in pregnant rabbits but not rats.

Vyvgart (efgartigimod alfa-fcab) (MW, 54k) is indicated to treat generalized myasthenia gravis. The drug did not cause birth defects in rats and rabbits.

Welireg (belzutifan) (MW, 383) is used to treat von Hippel–Lindau disease. In pregnant rats, the drug caused embryo-fetal lethality, reduced fetal body weight, and caused fetal skeletal malformations at maternal exposures of at least 0.2 times the human exposures.

Zegalogue (dasiglucagon) (MW, 3,382) is used to treat severe hypoglycemia. The drug did not cause birth defects in pregnant rats and rabbits.
 

Breastfeeding

It is not known if the above drugs will be in breast milk, but the safest course for an infant is to not breast feed if the mother is taking any of the above drugs.

Mr. Briggs is clinical professor of pharmacy at the University of California, San Francisco, and adjunct professor of pharmacy at the University of Southern California, Los Angeles, as well as at Washington State University, Spokane. Mr. Briggs said he had no relevant financial disclosures. Email him at [email protected].

In 2021, the Food and Drug Administration approved 50 new drugs, but 24 will not be described here because they would probably not be used in pregnancy. The 24 are Aduhelm (aducanumab) to treat Alzheimer’s disease; Azstarys (serdexmethylphenidate and dexmethylphenidate), a combination CNS stimulant indicated for the treatment of ADHD; Cabenuva (cabotegravir and rilpivirine) to treat HIV; Voxzogo (vosoritide) for children with achondroplasia and open epiphyses; Qelbree (viloxazine) used in children aged 6-17 years to treat ADHD; and Pylarify (piflufolastat) for prostate cancer. Other anticancer drugs that will not be covered are Cosela (trilaciclib), Cytalux (pafolacianine), Exkivity (mobocertinib); Fotivda (tivozanib), Jemperli (dostarlimab-gxly), Lumakras (sotorasib), Pepaxto (melphalan flufenamide), Rybrevant (amivantamab-vmjw), Rylaze (asparaginase erwinia chrysanthemi), Scemblix (asciminib), Tepmetko (tepotinib), Tivdak (tisotumab vedotin-tftv), Truseltiq (infigratinib), Ukoniq (umbralisib), and Zynlonta (loncastuximab tesirine-lpyl).

Skytrofa (lonapegsomatropin-tcgd) will not be described below because it is indicated to treat short stature and is unlikely to be used in pregnancy. Nextstellis (drospirenone and estetrol) is used to prevent pregnancy.

Typically, for new drugs there will be no published reports describing their use in pregnant women. That information will come much later. In the sections below, the indications, effects on pregnant animals, and the potential for harm of a fetus/embryo are described. However, the relevance of animal data to human pregnancies is not great.

Adbry (tralokinumab) (molecular weight [MW], 147 kilodaltons), is indicated for the treatment of moderate to severe atopic dermatitis in adult patients whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable. The drug did not harm fetal monkeys at doses that were 10 times the maximum recommended human dose.

Besremi (ropeginterferon alfa-2b-njft) (MW, 60 kDa) is an interferon alfa-2b indicated for the treatment of adults with polycythemia vera. It is given by subcutaneous injection every 2 weeks. Animal studies assessing reproductive toxicity have not been conducted. The manufacturer states that the drug may cause fetal harm and should be assumed to have abortifacient potential.

Brexafemme (ibrexafungerp) (MW, 922) is indicated for the treatment of vulvovaginal candidiasis. The drug was teratogenic in pregnant rabbits but not in pregnant rats. The manufacturer recommends females with reproductive potential should use effective contraception during treatment and for 4 days after the final dose.

Bylvay (odevixibat) (MW unknown) is indicated for the treatment of pruritus in patients aged 3 months and older. There are no human data regarding its use in pregnant women. The drug was teratogenic in pregnant rabbits. Although there are no data, the drug has low absorption following oral administration and breastfeeding is not expected to result in exposure of the infant.

Empaveli (pegcetacoplan) (MW, 44 kDa) is used to treat paroxysmal nocturnal hemoglobinuria. When the drug was given to pregnant cynomolgus monkeys there was an increase in abortions and stillbirths.

Evkeeza (evinacumab-dgnb) (MW, 146k) is used to treat homozygous familial hypercholesterolemia. The drug was teratogenic in rabbits but not rats.

Fexinidazole (MW not specified) is indicated to treat human African trypanosomiasis caused by the parasite Trypanosoma brucei gambiense. Additional information not available.

Kerendia (finerenone) (MW, 378), is indicated to reduce the risk of kidney and heart complications in chronic kidney disease associated with type 2 diabetes. The drug was teratogenic in rats.

Korsuva (difelikefalin) (MW, 679) is a kappa opioid–receptor agonist indicated for the treatment of moderate to severe pruritus associated with chronic kidney disease in adults undergoing hemodialysis. No adverse effects were observed in pregnant rats and rabbits. The limited human data on use of Korsuva in pregnant women are not sufficient to evaluate a drug associated risk for major birth defects or miscarriage.

Leqvio (inclisiran) (MW, 17,285) is indicated to treat heterozygous familial hypercholesterolemia or clinical atherosclerotic cardiovascular disease as an add-on therapy. The drug was not teratogenic in rats and rabbits.

Livmarli (maralixibat) (MW, 710) is indicated for the treatment of cholestatic pruritus associated with Alagille syndrome. Because systemic absorption is low, the recommended clinical dose is not expected to result in measurable fetal exposure. No effects on fetal rats were observed.

Livtencity (maribavir) (MW, 376) is used to treat posttransplant cytomegalovirus infection that has not responded to other treatment. Embryo/fetal survival was reduced in rats but not in rabbits at doses less then the human dose.

Lupkynis (voclosporin) (MW, 1,215) is used to treat nephritis. Avoid use of Lupkynis in pregnant women because of the alcohol content of the drug formulation. The drug was embryocidal and feticidal in rats and rabbits but with no treatment-related fetal malformations or variations.

Lybalvi (olanzapine and samidorphan) (MW, 312 and 505) is a combination drug used to treat schizophrenia and bipolar disorder. It was fetal toxic in pregnant rats and rabbits but with no evidence of malformations. There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to atypical antipsychotics, including this drug, during pregnancy. Health care providers are encouraged to register patients by contacting the National Pregnancy Registry for Atypical Antipsychotics at 1-866-961-2388 or visit the Reproductive Psychiatry Resource and Information Center of the MGH Center for Women’s Mental Health.

Nexviazyme (avalglucosidase alfa-ngpt) (MW, 124k) is a hydrolytic lysosomal glycogen-specific enzyme indicated for the treatment of patients aged 1 year and older with late-onset Pompe disease. The drug was not teratogenic in mice and rabbits.

Nulibry (fosdenopterin) (MW, 480) is used to reduce the risk of mortality in molybdenum cofactor deficiency type A. Studies have not been conducted in pregnant animals.

Ponvory (ponesimod) (MW, 461) is used to treat relapsing forms of multiple sclerosis. The drug caused severe adverse effects in pregnant rats and rabbits.

Qulipta (atogepant) (MW, 604) is indicated to prevent episodic migraines. It is embryo/fetal toxic in rats and rabbits.

Saphnelo (anifrolumab-fnia) (MW, 148k) is used to treat moderate to severe systemic lupus erythematosus along with standard therapy. In pregnant cynomolgus monkeys, there was no evidence of embryotoxicity or fetal malformations with exposures up to approximately 28 times the exposure at the maximum recommended human dose.

Tavneos (avacopan) (MW, 582) is indicated to treat severe active antineutrophil cytoplasmic autoantibody–associated vasculitis in combination with standard therapy including glucocorticoids. There appears to be an increased risk for hepatotoxicity. The drug caused no defects in hamsters and rabbits, but in rabbits there was an increase in abortions.

Tezspire (tezepelumab-ekko) (MW, 147k) is indicated to treat severe asthma as an add-on maintenance therapy. No adverse fetal effects were observed in pregnant cynomolgus monkeys.

Verquvo (vericiguat) (MW, 426) is used to mitigate the risk of cardiovascular death and hospitalization for chronic heart failure. The drug was teratogenic in pregnant rabbits but not rats.

Vyvgart (efgartigimod alfa-fcab) (MW, 54k) is indicated to treat generalized myasthenia gravis. The drug did not cause birth defects in rats and rabbits.

Welireg (belzutifan) (MW, 383) is used to treat von Hippel–Lindau disease. In pregnant rats, the drug caused embryo-fetal lethality, reduced fetal body weight, and caused fetal skeletal malformations at maternal exposures of at least 0.2 times the human exposures.

Zegalogue (dasiglucagon) (MW, 3,382) is used to treat severe hypoglycemia. The drug did not cause birth defects in pregnant rats and rabbits.
 

Breastfeeding

It is not known if the above drugs will be in breast milk, but the safest course for an infant is to not breast feed if the mother is taking any of the above drugs.

Mr. Briggs is clinical professor of pharmacy at the University of California, San Francisco, and adjunct professor of pharmacy at the University of Southern California, Los Angeles, as well as at Washington State University, Spokane. Mr. Briggs said he had no relevant financial disclosures. Email him at [email protected].