From the Editor

Schizophrenia is arguably the most serious psychiatric brain syndrome. It disables teens and young adults and robs them of their potential and life dreams. It is widely regarded as a hopeless illness.

But it does not have to be. The reason most patients with schizophrenia do not return to their baseline is because obsolete clinical management approaches, a carryover from the last century, continue to be used.

Approximately 20 years ago, psychiatric researchers made a major discovery: psychosis is a neurotoxic state, and each psychotic episode is associated with significant brain damage in both gray and white matter.¹ Based on that discovery, a more rational management of schizophrenia has emerged, focused on protecting patients from experiencing psychotic recurrence after the first-episode psychosis (FEP). In the past century, this strategy did not exist because psychiatrists were in a state of scientific ignorance, completely unaware that the malignant component of schizophrenia that leads to disability is psychotic relapses, the primary cause of which is very poor medication adherence after hospital discharge following the FEP.

Based on the emerging scientific evidence, here are 3 essential principles to halt the deterioration and bend the curve of outcomes in schizophrenia:

1. Minimize the duration of untreated psychosis (DUP)

Numerous studies have shown that the longer the DUP, the worse the outcome in schizophrenia.^2,3 It is therefore vital to shorten the DUP spanning the emergence of psychotic symptoms at home, prior to the first hospital admission.⁴ The DUP is often prolonged from weeks to months by a combination of anosognosia by the patient, who fails to recognize how pathological their hallucinations and delusions are, plus the stigma of mental illness, which leads parents to delay bringing their son or daughter for psychiatric evaluation and treatment.

Another reason for a prolonged DUP is the legal system’s governing of the initiation of antipsychotic medications for an acutely psychotic patient who does not believe he/she is sick, and who adamantly refuses to receive medications. Laws passed decades ago have not kept up with scientific advances about brain damage during the DUP. Instead of delegating the rapid administration of an antipsychotic medication to the psychiatric physician who evaluated and diagnosed a patient with acute psychosis, the legal system further prolongs the DUP by requiring the psychiatrist to go to court and have a judge order the administration of antipsychotic medications. Such a legal requirement that delays urgently needed treatment has never been imposed on neurologists when administering medication to an obtunded stroke patient. Yet psychosis damages brain tissue and must be treated as urgently as stroke.⁵

Perhaps the most common reason for a long DUP is the recurrent relapses of psychosis, almost always caused by the high nonadherence rate among patients with schizophrenia due to multiple factors related to the illness itself.⁶ Ensuring uninterrupted delivery of an antipsychotic to a patient’s brain is as important to maintaining remission in schizophrenia as uninterrupted insulin treatment is for an individual with diabetes. The only way to guarantee ongoing daily pharmacotherapy in schizophrenia and avoid a longer DUP and more brain damage is to use long-acting injectable (LAI) formulations of antipsychotic medications, which are infrequently used despite making eminent sense to protect patients from the tragic consequences of psychotic relapse.⁷

Continue to: Start very early use of LAIs

2. Start very early use of LAIs

There is no doubt that switching from an oral to an LAI antipsychotic immediately after hospital discharge for the FEP is the single most important medical decision psychiatrists can make for patients with schizophrenia.⁸ This is because disability in schizophrenia begins after the second episode, not the first.^9-11 Therefore, psychiatrists must behave like cardiologists,¹² who strive to prevent a second destructive myocardial infarction. Regrettably, 99.9% of psychiatric practitioners never start an LAI after the FEP, and usually wait until the patient experiences multiple relapses, after extensive gray matter atrophy and white matter disintegration have occurred due to the neuro­inflammation and oxidative stress (free radicals) that occur with every psychotic episode.^13,14 This clearly does not make clinical sense, but remains the standard current practice.

In oncology, chemotherapy is far more effective in Stage 1 cancer, immediately after the diagnosis is made, rather than in Stage 4, when the prognosis is very poor. Similarly, LAIs are best used in Stage 1 schizophrenia, which is the first episode (schizophrenia researchers now regard the illness as having stages).¹⁵ Unfortunately, it is now rare for patients with schizophrenia to be switched to LAI pharmacotherapy right after recovery from the FEP. Instead, LAIs are more commonly used in Stage 3 or Stage 4, when the brains of patients with chronic schizophrenia have been already structurally damaged, and functional disability had set in. Bending the cure of outcome in schizophrenia is only possible when LAIs are used very early to prevent the second episode.

The prevention of relapse by using LAIs in FEP is truly remarkable. Subotnik et al¹⁶ reported that only 5% of FEP patients who received an LAI antipsychotic relapsed, compared to 33% of those who received an oral formulation of the same antipsychotic (a 650% difference). It is frankly inexplicable why psychiatrists do not exploit the relapse-preventing properties of LAIs at the time of discharge after the FEP, and instead continue to perpetuate the use of prescribing oral tablets to patients who are incapable of full adherence and doomed to “self-destruct.” This was the practice model in the previous century, when there was total ignorance about the brain-damaging effects of psychosis, and no sense of urgency about preventing psychotic relapses and DUP. Psychiatrists regarded LAIs as a last resort instead of a life-saving first resort.

In addition to relapse prevention,¹⁷ the benefits of second-generation LAIs include neuroprotection¹⁸ and lower all-cause mortality,¹⁹ a remarkable triad of benefits for patients with schizophrenia.²⁰

3. Implement comprehensive psychosocial treatment

Most patients with schizophrenia do not have access to the array of psychosocial treatments that have been shown to be vital for rehabilitation following the FEP, just as physical rehabilitation is indispensable after the first stroke. Studies such as RAISE,²¹ which was funded by the National Institute of Mental Health, have demonstrated the value of psychosocial therapies (Table^21-23). Collaborative care with primary care physicians is also essential due to the high prevalence of metabolic disorders (obesity, diabetics, dyslipidemia, hypertension), which tend to be undertreated in patients with schizophrenia.²⁴

Finally, when patients continue to experience delusions and hallucinations despite full adherence (with LAIs), clozapine must be used. Like LAIs, clozapine is woefully under­utilized²⁵ despite having been shown to restore mental health and full recovery to many (but not all) patients written off as hopeless due to persistent and refractory psychotic symptoms.²⁶

If clinicians who treat schizophrenia implement these 3 steps in their FEP patients, they will be gratified to witness a more benign trajectory of schizophrenia, which I have personally seen. The curve can indeed be bent in favor of better outcomes. By using the 3 evidence-based steps described here, clinicians will realize that schizophrenia does not have to carry the label of “the worst disease affecting mankind,” as an editorial in a top-tier journal pessimistically stated over 3 decades ago.²⁷

Schizophrenia is arguably the most serious psychiatric brain syndrome. It disables teens and young adults and robs them of their potential and life dreams. It is widely regarded as a hopeless illness.

But it does not have to be. The reason most patients with schizophrenia do not return to their baseline is because obsolete clinical management approaches, a carryover from the last century, continue to be used.

Approximately 20 years ago, psychiatric researchers made a major discovery: psychosis is a neurotoxic state, and each psychotic episode is associated with significant brain damage in both gray and white matter.¹ Based on that discovery, a more rational management of schizophrenia has emerged, focused on protecting patients from experiencing psychotic recurrence after the first-episode psychosis (FEP). In the past century, this strategy did not exist because psychiatrists were in a state of scientific ignorance, completely unaware that the malignant component of schizophrenia that leads to disability is psychotic relapses, the primary cause of which is very poor medication adherence after hospital discharge following the FEP.

Based on the emerging scientific evidence, here are 3 essential principles to halt the deterioration and bend the curve of outcomes in schizophrenia:

1. Minimize the duration of untreated psychosis (DUP)

Numerous studies have shown that the longer the DUP, the worse the outcome in schizophrenia.^2,3 It is therefore vital to shorten the DUP spanning the emergence of psychotic symptoms at home, prior to the first hospital admission.⁴ The DUP is often prolonged from weeks to months by a combination of anosognosia by the patient, who fails to recognize how pathological their hallucinations and delusions are, plus the stigma of mental illness, which leads parents to delay bringing their son or daughter for psychiatric evaluation and treatment.

Another reason for a prolonged DUP is the legal system’s governing of the initiation of antipsychotic medications for an acutely psychotic patient who does not believe he/she is sick, and who adamantly refuses to receive medications. Laws passed decades ago have not kept up with scientific advances about brain damage during the DUP. Instead of delegating the rapid administration of an antipsychotic medication to the psychiatric physician who evaluated and diagnosed a patient with acute psychosis, the legal system further prolongs the DUP by requiring the psychiatrist to go to court and have a judge order the administration of antipsychotic medications. Such a legal requirement that delays urgently needed treatment has never been imposed on neurologists when administering medication to an obtunded stroke patient. Yet psychosis damages brain tissue and must be treated as urgently as stroke.⁵

Perhaps the most common reason for a long DUP is the recurrent relapses of psychosis, almost always caused by the high nonadherence rate among patients with schizophrenia due to multiple factors related to the illness itself.⁶ Ensuring uninterrupted delivery of an antipsychotic to a patient’s brain is as important to maintaining remission in schizophrenia as uninterrupted insulin treatment is for an individual with diabetes. The only way to guarantee ongoing daily pharmacotherapy in schizophrenia and avoid a longer DUP and more brain damage is to use long-acting injectable (LAI) formulations of antipsychotic medications, which are infrequently used despite making eminent sense to protect patients from the tragic consequences of psychotic relapse.⁷

Continue to: Start very early use of LAIs

2. Start very early use of LAIs

There is no doubt that switching from an oral to an LAI antipsychotic immediately after hospital discharge for the FEP is the single most important medical decision psychiatrists can make for patients with schizophrenia.⁸ This is because disability in schizophrenia begins after the second episode, not the first.^9-11 Therefore, psychiatrists must behave like cardiologists,¹² who strive to prevent a second destructive myocardial infarction. Regrettably, 99.9% of psychiatric practitioners never start an LAI after the FEP, and usually wait until the patient experiences multiple relapses, after extensive gray matter atrophy and white matter disintegration have occurred due to the neuro­inflammation and oxidative stress (free radicals) that occur with every psychotic episode.^13,14 This clearly does not make clinical sense, but remains the standard current practice.

In oncology, chemotherapy is far more effective in Stage 1 cancer, immediately after the diagnosis is made, rather than in Stage 4, when the prognosis is very poor. Similarly, LAIs are best used in Stage 1 schizophrenia, which is the first episode (schizophrenia researchers now regard the illness as having stages).¹⁵ Unfortunately, it is now rare for patients with schizophrenia to be switched to LAI pharmacotherapy right after recovery from the FEP. Instead, LAIs are more commonly used in Stage 3 or Stage 4, when the brains of patients with chronic schizophrenia have been already structurally damaged, and functional disability had set in. Bending the cure of outcome in schizophrenia is only possible when LAIs are used very early to prevent the second episode.

The prevention of relapse by using LAIs in FEP is truly remarkable. Subotnik et al¹⁶ reported that only 5% of FEP patients who received an LAI antipsychotic relapsed, compared to 33% of those who received an oral formulation of the same antipsychotic (a 650% difference). It is frankly inexplicable why psychiatrists do not exploit the relapse-preventing properties of LAIs at the time of discharge after the FEP, and instead continue to perpetuate the use of prescribing oral tablets to patients who are incapable of full adherence and doomed to “self-destruct.” This was the practice model in the previous century, when there was total ignorance about the brain-damaging effects of psychosis, and no sense of urgency about preventing psychotic relapses and DUP. Psychiatrists regarded LAIs as a last resort instead of a life-saving first resort.

In addition to relapse prevention,¹⁷ the benefits of second-generation LAIs include neuroprotection¹⁸ and lower all-cause mortality,¹⁹ a remarkable triad of benefits for patients with schizophrenia.²⁰

3. Implement comprehensive psychosocial treatment

Most patients with schizophrenia do not have access to the array of psychosocial treatments that have been shown to be vital for rehabilitation following the FEP, just as physical rehabilitation is indispensable after the first stroke. Studies such as RAISE,²¹ which was funded by the National Institute of Mental Health, have demonstrated the value of psychosocial therapies (Table^21-23). Collaborative care with primary care physicians is also essential due to the high prevalence of metabolic disorders (obesity, diabetics, dyslipidemia, hypertension), which tend to be undertreated in patients with schizophrenia.²⁴

Finally, when patients continue to experience delusions and hallucinations despite full adherence (with LAIs), clozapine must be used. Like LAIs, clozapine is woefully under­utilized²⁵ despite having been shown to restore mental health and full recovery to many (but not all) patients written off as hopeless due to persistent and refractory psychotic symptoms.²⁶

If clinicians who treat schizophrenia implement these 3 steps in their FEP patients, they will be gratified to witness a more benign trajectory of schizophrenia, which I have personally seen. The curve can indeed be bent in favor of better outcomes. By using the 3 evidence-based steps described here, clinicians will realize that schizophrenia does not have to carry the label of “the worst disease affecting mankind,” as an editorial in a top-tier journal pessimistically stated over 3 decades ago.²⁷

Schizophrenia is arguably the most serious psychiatric brain syndrome. It disables teens and young adults and robs them of their potential and life dreams. It is widely regarded as a hopeless illness.

But it does not have to be. The reason most patients with schizophrenia do not return to their baseline is because obsolete clinical management approaches, a carryover from the last century, continue to be used.

Approximately 20 years ago, psychiatric researchers made a major discovery: psychosis is a neurotoxic state, and each psychotic episode is associated with significant brain damage in both gray and white matter.¹ Based on that discovery, a more rational management of schizophrenia has emerged, focused on protecting patients from experiencing psychotic recurrence after the first-episode psychosis (FEP). In the past century, this strategy did not exist because psychiatrists were in a state of scientific ignorance, completely unaware that the malignant component of schizophrenia that leads to disability is psychotic relapses, the primary cause of which is very poor medication adherence after hospital discharge following the FEP.

Based on the emerging scientific evidence, here are 3 essential principles to halt the deterioration and bend the curve of outcomes in schizophrenia:

1. Minimize the duration of untreated psychosis (DUP)

Numerous studies have shown that the longer the DUP, the worse the outcome in schizophrenia.^2,3 It is therefore vital to shorten the DUP spanning the emergence of psychotic symptoms at home, prior to the first hospital admission.⁴ The DUP is often prolonged from weeks to months by a combination of anosognosia by the patient, who fails to recognize how pathological their hallucinations and delusions are, plus the stigma of mental illness, which leads parents to delay bringing their son or daughter for psychiatric evaluation and treatment.

Another reason for a prolonged DUP is the legal system’s governing of the initiation of antipsychotic medications for an acutely psychotic patient who does not believe he/she is sick, and who adamantly refuses to receive medications. Laws passed decades ago have not kept up with scientific advances about brain damage during the DUP. Instead of delegating the rapid administration of an antipsychotic medication to the psychiatric physician who evaluated and diagnosed a patient with acute psychosis, the legal system further prolongs the DUP by requiring the psychiatrist to go to court and have a judge order the administration of antipsychotic medications. Such a legal requirement that delays urgently needed treatment has never been imposed on neurologists when administering medication to an obtunded stroke patient. Yet psychosis damages brain tissue and must be treated as urgently as stroke.⁵

Perhaps the most common reason for a long DUP is the recurrent relapses of psychosis, almost always caused by the high nonadherence rate among patients with schizophrenia due to multiple factors related to the illness itself.⁶ Ensuring uninterrupted delivery of an antipsychotic to a patient’s brain is as important to maintaining remission in schizophrenia as uninterrupted insulin treatment is for an individual with diabetes. The only way to guarantee ongoing daily pharmacotherapy in schizophrenia and avoid a longer DUP and more brain damage is to use long-acting injectable (LAI) formulations of antipsychotic medications, which are infrequently used despite making eminent sense to protect patients from the tragic consequences of psychotic relapse.⁷

Continue to: Start very early use of LAIs

2. Start very early use of LAIs

There is no doubt that switching from an oral to an LAI antipsychotic immediately after hospital discharge for the FEP is the single most important medical decision psychiatrists can make for patients with schizophrenia.⁸ This is because disability in schizophrenia begins after the second episode, not the first.^9-11 Therefore, psychiatrists must behave like cardiologists,¹² who strive to prevent a second destructive myocardial infarction. Regrettably, 99.9% of psychiatric practitioners never start an LAI after the FEP, and usually wait until the patient experiences multiple relapses, after extensive gray matter atrophy and white matter disintegration have occurred due to the neuro­inflammation and oxidative stress (free radicals) that occur with every psychotic episode.^13,14 This clearly does not make clinical sense, but remains the standard current practice.

In oncology, chemotherapy is far more effective in Stage 1 cancer, immediately after the diagnosis is made, rather than in Stage 4, when the prognosis is very poor. Similarly, LAIs are best used in Stage 1 schizophrenia, which is the first episode (schizophrenia researchers now regard the illness as having stages).¹⁵ Unfortunately, it is now rare for patients with schizophrenia to be switched to LAI pharmacotherapy right after recovery from the FEP. Instead, LAIs are more commonly used in Stage 3 or Stage 4, when the brains of patients with chronic schizophrenia have been already structurally damaged, and functional disability had set in. Bending the cure of outcome in schizophrenia is only possible when LAIs are used very early to prevent the second episode.

The prevention of relapse by using LAIs in FEP is truly remarkable. Subotnik et al¹⁶ reported that only 5% of FEP patients who received an LAI antipsychotic relapsed, compared to 33% of those who received an oral formulation of the same antipsychotic (a 650% difference). It is frankly inexplicable why psychiatrists do not exploit the relapse-preventing properties of LAIs at the time of discharge after the FEP, and instead continue to perpetuate the use of prescribing oral tablets to patients who are incapable of full adherence and doomed to “self-destruct.” This was the practice model in the previous century, when there was total ignorance about the brain-damaging effects of psychosis, and no sense of urgency about preventing psychotic relapses and DUP. Psychiatrists regarded LAIs as a last resort instead of a life-saving first resort.

In addition to relapse prevention,¹⁷ the benefits of second-generation LAIs include neuroprotection¹⁸ and lower all-cause mortality,¹⁹ a remarkable triad of benefits for patients with schizophrenia.²⁰

3. Implement comprehensive psychosocial treatment

Most patients with schizophrenia do not have access to the array of psychosocial treatments that have been shown to be vital for rehabilitation following the FEP, just as physical rehabilitation is indispensable after the first stroke. Studies such as RAISE,²¹ which was funded by the National Institute of Mental Health, have demonstrated the value of psychosocial therapies (Table^21-23). Collaborative care with primary care physicians is also essential due to the high prevalence of metabolic disorders (obesity, diabetics, dyslipidemia, hypertension), which tend to be undertreated in patients with schizophrenia.²⁴

Finally, when patients continue to experience delusions and hallucinations despite full adherence (with LAIs), clozapine must be used. Like LAIs, clozapine is woefully under­utilized²⁵ despite having been shown to restore mental health and full recovery to many (but not all) patients written off as hopeless due to persistent and refractory psychotic symptoms.²⁶

If clinicians who treat schizophrenia implement these 3 steps in their FEP patients, they will be gratified to witness a more benign trajectory of schizophrenia, which I have personally seen. The curve can indeed be bent in favor of better outcomes. By using the 3 evidence-based steps described here, clinicians will realize that schizophrenia does not have to carry the label of “the worst disease affecting mankind,” as an editorial in a top-tier journal pessimistically stated over 3 decades ago.²⁷

Having witnessed the devastating impact of stigma on patients with mental illness throughout my psychiatric career, I am fed up and disgusted with this malevolent scourge.

I regard the stigma that engulfs neuropsychiatric disorders as a malignancy that mutilates patients’ souls and hastens their mortality.

Stigma is hate speech

How would you feel if you had a serious medical illness, a disabling brain disorder such as schizophrenia, depression, or anxiety, and people refer to you with pejorative and insulting terms such as crazy, deranged, lunatic, unhinged, nutty, insane, wacky, berserk, cuckoo, bonkers, flaky, screwball, or unglued? This is hate speech generated by stigma against people with mental illness. Individuals with heart disease, cancer, or diabetes never get called such disgraceful and stigmatizing terms that shame, stain, besmirch, and scar them, which happens daily to persons with psychiatric brain disorders.

The damage and harm of the discriminatory stigma on our patients is multifaceted. It is painful, detrimental, pernicious, and deleterious. It is corrosive to their spirits, crippling to their self-image, and subversive to their self-confidence. Hate speech is not simply words, but a menacing weapon that assaults the core humanity of medically ill psychiatric patients.

Although hate speech is punishable by law, there are rarely any legal actions against those who hurl hate speech at psychiatric patients every day. Society has institutionalized the stigma of mental illness and takes it in stride instead of recognizing it as an illegal, harmful act.

Long before the stresses of the COVID-19 pandemic, 43% of the population had been shown to experience a diagnosable psychiatric disorder over the course of their life.¹ Thus, tens of millions of people are burdened by stigma and the hate speech associated with it. This is directly related to massive ignorance about mental illness being the result of a neurobiological condition due to either genetic or intrauterine adverse events that disrupt brain development. Delusions and hallucinations are symptoms of a malfunctioning brain, depression is not a sign of personal weakness, anxiety is the most prevalent mental disorder in the world, and obsessive-compulsive disorder (OCD) is not odd behavior but the result of dysfunction of neural circuits. Correcting public misperceptions about psychiatric brain disorders can mitigate stigma, but it has yet to happen.

Stigma is a hate crime

Stigma can accelerate physical death and premature mortality. Many studies have confirmed that persons with schizophrenia do not receive basic primary care treatments for the life-shortening medical conditions that often afflict them, such as diabetes, dyslipidemia, and hypertension.² Stigma is responsible for a significant disparity of medical^3-5 and intensive care⁶ among individuals with mental illness compared to the general population. It’s no wonder most psychiatric disorders are associated with accelerated mortality.⁷ A recent study during the pandemic by Balasuriya et al⁸ reported that patients with depression had poor access to care. Stigma interferes with or delays necessary medical care, leading to clinical deterioration and unnecessary, preventable death. Stigma shortens life and is a hate crime.

Continue to: The extremely high suicide rates...

The extremely high suicide rates among individuals with serious mental illness, who live under the oppressiveness of stigma, is another example of how stigma is a hate crime that can cause patients with psychiatric disorders to give up and end their lives. Zaheer et al⁹ found that young patients with schizophrenia had an astronomical suicide rate compared to the general population (1 in 52 in individuals with schizophrenia, compared to 12 in 100,000 in the general population, roughly a 200-fold increase!). This is clearly a consequence of stigma and discrimination,¹⁰ which leads to demoralization, shame, loneliness, distress, and hopelessness. Stigma can be fatal, and that makes it a hate crime.

Stigma also limits vocational opportunities for individuals with mental illness. They are either not hired, or quickly fired. Even highly educated professionals such as physicians, nurses, lawyers, or teachers can lose their jobs if they divulge a history of a psychiatric disorder or alcohol or substance abuse, regardless of whether they are receiving treatment and are medically in remission. Even highly qualified politicians have been deemed “ineligible” for higher office if they disclose a history of psychiatric treatment. Stigma is loaded with outrageous discrimination that deprives our patients of “the pursuit of happiness,” a fundamental constitutional right.

Stigma surrounding the mental health professions

Stigma also engulfs mental health professionals, simply because they deal with psychiatric patients every day. In a classic article titled “The Enigma of Stigma,”¹¹ Dr. Paul Fink, past president of the American Psychiatric Association (1988-1989), described how psychiatrists are perceived as “different” from other physicians by the public and by the media. He said psychiatrists are tarred by the same brush as their patients as “undesirables” in society. And movies such as Psycho and One Flew Over the Cuckoo’s Nest reinforce the stigma against both psychiatric patients and the psychiatrists and nurses who treat them. The health care system that carves out “behavioral health” from the umbrella of “medical care” further accentuates the stigma by portraying the “separateness” of psychiatry, a genuine medical specialty, from its fellow medical disciplines. This becomes fodder for the antipsychiatry movement at every turn and can even lead to questioning the existence of mental illness, as Thomas Szasz¹² did by declaring that mental illness is a myth and describing psychiatry as “the science of lies.” No other medical specialty endures abuse and insults like psychiatry, and that’s a direct result of stigma.

Extinguishing stigma is a societal imperative

So what can be done to squelch stigma and defeat it once and for all, so that psychiatric patients can be treated with dignity and compassion, like people with cancer, heart attacks, diabetes, or brain tumors? The pandemic, terrible as it has been for the entire world, did have the silver lining of raising awareness about the ubiquity of psychiatric symptoms, such as anxiety and depression, across all ages, genders, educational and religious backgrounds, and socioeconomic classes. But there should also be a robust legal battle against the damaging effects of stigma. There are laws to sanction and penalize hate speech and hate crimes that must be implemented when stigma is documented. There are also parity laws, but they have no teeth and have not ameliorated the insurance discrepancies and economic burden of psychiatric disorders. A bold step would be to reclassify serious psychiatric brain disorders (schizophrenia, bipolar disorder, major depressive disorder, OCD, attention-deficit/hyperactivity disorder, generalized anxiety disorder/panic attacks, and borderline personality disorder) as neurologic disorders, which would automatically give patients with these disorders broad access to medical care, which happened when autism was reclassified as a neurologic disorder. Finally, a much more intensive public education must be disseminated about the neurobiological etiologies, brain structure, and function in psychiatric disorders, and the psychiatric symptoms associated with all neurologic disorders. Regrettably, empathy can be difficult to teach.

Stigma is hate speech and a hate crime. It must be permanently eliminated by effective laws and by erasing the widespread ignorance about the medical and neurologic roots of mental disorders, and by emphasizing the fact that they are as treatable as other general medical conditions.

Having witnessed the devastating impact of stigma on patients with mental illness throughout my psychiatric career, I am fed up and disgusted with this malevolent scourge.

I regard the stigma that engulfs neuropsychiatric disorders as a malignancy that mutilates patients’ souls and hastens their mortality.

Stigma is hate speech

How would you feel if you had a serious medical illness, a disabling brain disorder such as schizophrenia, depression, or anxiety, and people refer to you with pejorative and insulting terms such as crazy, deranged, lunatic, unhinged, nutty, insane, wacky, berserk, cuckoo, bonkers, flaky, screwball, or unglued? This is hate speech generated by stigma against people with mental illness. Individuals with heart disease, cancer, or diabetes never get called such disgraceful and stigmatizing terms that shame, stain, besmirch, and scar them, which happens daily to persons with psychiatric brain disorders.

The damage and harm of the discriminatory stigma on our patients is multifaceted. It is painful, detrimental, pernicious, and deleterious. It is corrosive to their spirits, crippling to their self-image, and subversive to their self-confidence. Hate speech is not simply words, but a menacing weapon that assaults the core humanity of medically ill psychiatric patients.

Although hate speech is punishable by law, there are rarely any legal actions against those who hurl hate speech at psychiatric patients every day. Society has institutionalized the stigma of mental illness and takes it in stride instead of recognizing it as an illegal, harmful act.

Long before the stresses of the COVID-19 pandemic, 43% of the population had been shown to experience a diagnosable psychiatric disorder over the course of their life.¹ Thus, tens of millions of people are burdened by stigma and the hate speech associated with it. This is directly related to massive ignorance about mental illness being the result of a neurobiological condition due to either genetic or intrauterine adverse events that disrupt brain development. Delusions and hallucinations are symptoms of a malfunctioning brain, depression is not a sign of personal weakness, anxiety is the most prevalent mental disorder in the world, and obsessive-compulsive disorder (OCD) is not odd behavior but the result of dysfunction of neural circuits. Correcting public misperceptions about psychiatric brain disorders can mitigate stigma, but it has yet to happen.

Stigma is a hate crime

Stigma can accelerate physical death and premature mortality. Many studies have confirmed that persons with schizophrenia do not receive basic primary care treatments for the life-shortening medical conditions that often afflict them, such as diabetes, dyslipidemia, and hypertension.² Stigma is responsible for a significant disparity of medical^3-5 and intensive care⁶ among individuals with mental illness compared to the general population. It’s no wonder most psychiatric disorders are associated with accelerated mortality.⁷ A recent study during the pandemic by Balasuriya et al⁸ reported that patients with depression had poor access to care. Stigma interferes with or delays necessary medical care, leading to clinical deterioration and unnecessary, preventable death. Stigma shortens life and is a hate crime.

Continue to: The extremely high suicide rates...

The extremely high suicide rates among individuals with serious mental illness, who live under the oppressiveness of stigma, is another example of how stigma is a hate crime that can cause patients with psychiatric disorders to give up and end their lives. Zaheer et al⁹ found that young patients with schizophrenia had an astronomical suicide rate compared to the general population (1 in 52 in individuals with schizophrenia, compared to 12 in 100,000 in the general population, roughly a 200-fold increase!). This is clearly a consequence of stigma and discrimination,¹⁰ which leads to demoralization, shame, loneliness, distress, and hopelessness. Stigma can be fatal, and that makes it a hate crime.

Stigma also limits vocational opportunities for individuals with mental illness. They are either not hired, or quickly fired. Even highly educated professionals such as physicians, nurses, lawyers, or teachers can lose their jobs if they divulge a history of a psychiatric disorder or alcohol or substance abuse, regardless of whether they are receiving treatment and are medically in remission. Even highly qualified politicians have been deemed “ineligible” for higher office if they disclose a history of psychiatric treatment. Stigma is loaded with outrageous discrimination that deprives our patients of “the pursuit of happiness,” a fundamental constitutional right.

Stigma surrounding the mental health professions

Stigma also engulfs mental health professionals, simply because they deal with psychiatric patients every day. In a classic article titled “The Enigma of Stigma,”¹¹ Dr. Paul Fink, past president of the American Psychiatric Association (1988-1989), described how psychiatrists are perceived as “different” from other physicians by the public and by the media. He said psychiatrists are tarred by the same brush as their patients as “undesirables” in society. And movies such as Psycho and One Flew Over the Cuckoo’s Nest reinforce the stigma against both psychiatric patients and the psychiatrists and nurses who treat them. The health care system that carves out “behavioral health” from the umbrella of “medical care” further accentuates the stigma by portraying the “separateness” of psychiatry, a genuine medical specialty, from its fellow medical disciplines. This becomes fodder for the antipsychiatry movement at every turn and can even lead to questioning the existence of mental illness, as Thomas Szasz¹² did by declaring that mental illness is a myth and describing psychiatry as “the science of lies.” No other medical specialty endures abuse and insults like psychiatry, and that’s a direct result of stigma.

Extinguishing stigma is a societal imperative

So what can be done to squelch stigma and defeat it once and for all, so that psychiatric patients can be treated with dignity and compassion, like people with cancer, heart attacks, diabetes, or brain tumors? The pandemic, terrible as it has been for the entire world, did have the silver lining of raising awareness about the ubiquity of psychiatric symptoms, such as anxiety and depression, across all ages, genders, educational and religious backgrounds, and socioeconomic classes. But there should also be a robust legal battle against the damaging effects of stigma. There are laws to sanction and penalize hate speech and hate crimes that must be implemented when stigma is documented. There are also parity laws, but they have no teeth and have not ameliorated the insurance discrepancies and economic burden of psychiatric disorders. A bold step would be to reclassify serious psychiatric brain disorders (schizophrenia, bipolar disorder, major depressive disorder, OCD, attention-deficit/hyperactivity disorder, generalized anxiety disorder/panic attacks, and borderline personality disorder) as neurologic disorders, which would automatically give patients with these disorders broad access to medical care, which happened when autism was reclassified as a neurologic disorder. Finally, a much more intensive public education must be disseminated about the neurobiological etiologies, brain structure, and function in psychiatric disorders, and the psychiatric symptoms associated with all neurologic disorders. Regrettably, empathy can be difficult to teach.

Stigma is hate speech and a hate crime. It must be permanently eliminated by effective laws and by erasing the widespread ignorance about the medical and neurologic roots of mental disorders, and by emphasizing the fact that they are as treatable as other general medical conditions.

Having witnessed the devastating impact of stigma on patients with mental illness throughout my psychiatric career, I am fed up and disgusted with this malevolent scourge.

I regard the stigma that engulfs neuropsychiatric disorders as a malignancy that mutilates patients’ souls and hastens their mortality.

Stigma is hate speech

How would you feel if you had a serious medical illness, a disabling brain disorder such as schizophrenia, depression, or anxiety, and people refer to you with pejorative and insulting terms such as crazy, deranged, lunatic, unhinged, nutty, insane, wacky, berserk, cuckoo, bonkers, flaky, screwball, or unglued? This is hate speech generated by stigma against people with mental illness. Individuals with heart disease, cancer, or diabetes never get called such disgraceful and stigmatizing terms that shame, stain, besmirch, and scar them, which happens daily to persons with psychiatric brain disorders.

The damage and harm of the discriminatory stigma on our patients is multifaceted. It is painful, detrimental, pernicious, and deleterious. It is corrosive to their spirits, crippling to their self-image, and subversive to their self-confidence. Hate speech is not simply words, but a menacing weapon that assaults the core humanity of medically ill psychiatric patients.

Although hate speech is punishable by law, there are rarely any legal actions against those who hurl hate speech at psychiatric patients every day. Society has institutionalized the stigma of mental illness and takes it in stride instead of recognizing it as an illegal, harmful act.

Long before the stresses of the COVID-19 pandemic, 43% of the population had been shown to experience a diagnosable psychiatric disorder over the course of their life.¹ Thus, tens of millions of people are burdened by stigma and the hate speech associated with it. This is directly related to massive ignorance about mental illness being the result of a neurobiological condition due to either genetic or intrauterine adverse events that disrupt brain development. Delusions and hallucinations are symptoms of a malfunctioning brain, depression is not a sign of personal weakness, anxiety is the most prevalent mental disorder in the world, and obsessive-compulsive disorder (OCD) is not odd behavior but the result of dysfunction of neural circuits. Correcting public misperceptions about psychiatric brain disorders can mitigate stigma, but it has yet to happen.

Stigma is a hate crime

Stigma can accelerate physical death and premature mortality. Many studies have confirmed that persons with schizophrenia do not receive basic primary care treatments for the life-shortening medical conditions that often afflict them, such as diabetes, dyslipidemia, and hypertension.² Stigma is responsible for a significant disparity of medical^3-5 and intensive care⁶ among individuals with mental illness compared to the general population. It’s no wonder most psychiatric disorders are associated with accelerated mortality.⁷ A recent study during the pandemic by Balasuriya et al⁸ reported that patients with depression had poor access to care. Stigma interferes with or delays necessary medical care, leading to clinical deterioration and unnecessary, preventable death. Stigma shortens life and is a hate crime.

Continue to: The extremely high suicide rates...

The extremely high suicide rates among individuals with serious mental illness, who live under the oppressiveness of stigma, is another example of how stigma is a hate crime that can cause patients with psychiatric disorders to give up and end their lives. Zaheer et al⁹ found that young patients with schizophrenia had an astronomical suicide rate compared to the general population (1 in 52 in individuals with schizophrenia, compared to 12 in 100,000 in the general population, roughly a 200-fold increase!). This is clearly a consequence of stigma and discrimination,¹⁰ which leads to demoralization, shame, loneliness, distress, and hopelessness. Stigma can be fatal, and that makes it a hate crime.

Stigma also limits vocational opportunities for individuals with mental illness. They are either not hired, or quickly fired. Even highly educated professionals such as physicians, nurses, lawyers, or teachers can lose their jobs if they divulge a history of a psychiatric disorder or alcohol or substance abuse, regardless of whether they are receiving treatment and are medically in remission. Even highly qualified politicians have been deemed “ineligible” for higher office if they disclose a history of psychiatric treatment. Stigma is loaded with outrageous discrimination that deprives our patients of “the pursuit of happiness,” a fundamental constitutional right.

Stigma surrounding the mental health professions

Stigma also engulfs mental health professionals, simply because they deal with psychiatric patients every day. In a classic article titled “The Enigma of Stigma,”¹¹ Dr. Paul Fink, past president of the American Psychiatric Association (1988-1989), described how psychiatrists are perceived as “different” from other physicians by the public and by the media. He said psychiatrists are tarred by the same brush as their patients as “undesirables” in society. And movies such as Psycho and One Flew Over the Cuckoo’s Nest reinforce the stigma against both psychiatric patients and the psychiatrists and nurses who treat them. The health care system that carves out “behavioral health” from the umbrella of “medical care” further accentuates the stigma by portraying the “separateness” of psychiatry, a genuine medical specialty, from its fellow medical disciplines. This becomes fodder for the antipsychiatry movement at every turn and can even lead to questioning the existence of mental illness, as Thomas Szasz¹² did by declaring that mental illness is a myth and describing psychiatry as “the science of lies.” No other medical specialty endures abuse and insults like psychiatry, and that’s a direct result of stigma.

Extinguishing stigma is a societal imperative

So what can be done to squelch stigma and defeat it once and for all, so that psychiatric patients can be treated with dignity and compassion, like people with cancer, heart attacks, diabetes, or brain tumors? The pandemic, terrible as it has been for the entire world, did have the silver lining of raising awareness about the ubiquity of psychiatric symptoms, such as anxiety and depression, across all ages, genders, educational and religious backgrounds, and socioeconomic classes. But there should also be a robust legal battle against the damaging effects of stigma. There are laws to sanction and penalize hate speech and hate crimes that must be implemented when stigma is documented. There are also parity laws, but they have no teeth and have not ameliorated the insurance discrepancies and economic burden of psychiatric disorders. A bold step would be to reclassify serious psychiatric brain disorders (schizophrenia, bipolar disorder, major depressive disorder, OCD, attention-deficit/hyperactivity disorder, generalized anxiety disorder/panic attacks, and borderline personality disorder) as neurologic disorders, which would automatically give patients with these disorders broad access to medical care, which happened when autism was reclassified as a neurologic disorder. Finally, a much more intensive public education must be disseminated about the neurobiological etiologies, brain structure, and function in psychiatric disorders, and the psychiatric symptoms associated with all neurologic disorders. Regrettably, empathy can be difficult to teach.

Stigma is hate speech and a hate crime. It must be permanently eliminated by effective laws and by erasing the widespread ignorance about the medical and neurologic roots of mental disorders, and by emphasizing the fact that they are as treatable as other general medical conditions.

During pregnancy, anemia and iron deficiency are prevalent because the fetus depletes maternal iron stores. Iron deficiency and iron deficiency anemia are not synonymous. Effective screening for iron deficiency in the first trimester of pregnancy requires the measurement of a sensitive and specific biomarker of iron deficiency, such as ferritin. Limiting the measurement of ferritin to the subset of patients with anemia will result in missing many cases of iron deficiency. By the time iron deficiency causes anemia, a severe deficiency is present. Detecting iron deficiency in pregnancy and promptly treating the deficiency will reduce the number of women with anemia in the third trimester and at birth.

Diagnosis of anemia

Anemia in pregnancy is diagnosed by a hemoglobin level and hematocrit concentration below 11 g/dL and 33%, respectively, in the first and third trimesters and below 10.5 g/dL and 32%, respectively, in the second trimester.¹ The prevalence of anemia in the first, second, and third trimesters is approximately 3%, 2%, and 11%, respectively.² At a hemoglobin concentration <11 g/dL, severe maternal morbidity rises significantly.³ The laboratory evaluation of pregnant women with anemia may require assessment of iron stores, measurement of folate and cobalamin (vitamin B12), and hemoglobin electrophoresis, if indicated.

Diagnosis of iron deficiency

Iron deficiency anemia is diagnosed by a ferritin level below 30 ng/mL.^4,5 Normal iron stores and iron insufficiency are indicated by ferritin levels 45 to 150 ng/mL and 30 to 44 ng/mL, respectively.^4,5 Ferritin is an acute phase reactant, and patients with inflammation or chronic illnesses may have iron deficiency and a normal ferritin level. For these patients, a transferrin saturation (TSAT) <16% would support a diagnosis of iron deficiency.⁶ TSAT is calculated from measurement of serum iron and total iron binding capacity. TSAT saturation may be elevated by iron supplements, which increase serum iron. If measurement of TSAT is necessary, interference with the measurement accuracy can be minimized by not taking an iron supplement on the day of testing.

Iron deficiency is present in approximately 50% of pregnant women.^7,8 The greatest prevalence of iron deficiency in pregnancy is observed in non-Hispanic Black females, followed by Hispanic females. Non-Hispanic White females had the lowest prevalence of iron deficiency.²

Fetal needs for iron often cause the depletion of maternal iron stores. Many pregnant women who have a normal ferritin level in the first trimester will develop iron deficiency in the third trimester, even with the usual recommended daily oral iron supplementation. We recommend measuring ferritin and hemoglobin at the first prenatal visit and again between 24 and 28 weeks’ gestation.

Impact of maternal anemia on maternal and newborn health

Iron plays a critical role in maternal health and fetal development independent of its role in red blood cell formation. Many proteins critical to maternal health and fetal development contain iron, including hemoglobin, myoglobin, cytochromes, ribonucleotide reductase, peroxidases, lipoxygenases, and cyclooxygenases. In the fetus, iron plays an important role in myelination of nerves, dendrite arborization, and synthesis of monoamine neurotransmitters.⁹

Many studies report that maternal anemia is associated with severe maternal morbidity and adverse newborn outcomes. The current literature must be interpreted with caution because socioeconomic factors influence iron stores. Iron deficiency and anemia is more common among economically and socially disadvantaged populations.^10-12 It is possible that repleting iron stores, alone, without addressing social determinants of health, including food and housing insecurity, may be insufficient to improve maternal and newborn health.

Maternal anemia is a risk factor for severe maternal morbidity and adverse newborn outcomes.^3,13-18 In a study of 515,270 live births in British Columbia between 2004 and 2016, maternal anemia was diagnosed in 12.8% of mothers.¹⁵ Maternal morbidity at birth was increased among patients with mild anemia (hemoglobin concentration of 9 to 10.9 g/dL), including higher rates of intrapartum transfusion (adjusted odds ratio [OR], 2.45; 95% confidence interval [CI], 1.74-3.45), cesarean birth (aOR, 1.17; 95% CI, 1.14-1.19), and chorioamnionitis (aOR, 1.35; 95% CI, 1.27-1.44). Newborn morbidity was also increased among newborns of mothers with mild anemia (hemoglobin concentrations of 9 to 10.9 g/dL), including birth before 37 weeks’ gestation (aOR, 1.09; 95% CI, 1.05-1.12), birth before 32 weeks’ gestation (aOR, 1.30; 95% CI, 1.21-1.39), admission to the intensive care unit (aOR, 1.21; 95% CI, 1.17-1.25), and respiratory distress syndrome (aOR, 1.35; 95% CI, 1.24-1.46).¹⁵ Adverse maternal and newborn outcomes were more prevalent among mothers with moderate (hemoglobin concentrations of 7 to 8.9 g/dL) or severe anemia (hemoglobin concentrations of <7 g/dL), compared with mild anemia. For example, compared with mothers with no anemia, mothers with moderate anemia had an increased risk of birth <37 weeks (aOR, 2.26) and birth <32 weeks (aOR, 3.95).¹⁵

In a study of 166,566 US pregnant patients, 6.1% were diagnosed with anemia.¹⁸ Patients with anemia were more likely to have antepartum thrombosis, preeclampsia, eclampsia, a cesarean birth, postpartum hemorrhage, a blood transfusion, and postpartum thrombosis.¹⁸ In this study, the newborns of mothers with anemia were more likely to have a diagnosis of antenatal or intrapartum fetal distress, a 5-minute Apgar score <7, and an admission to the neonatal intensive care unit.

Continue to: Maternal anemia and neurodevelopmental disorders in children...

Some experts, but not all, believe that iron deficiency during pregnancy may adversely impact fetal neurodevelopment and result in childhood behavior issues. All experts agree that more research is needed to understand if maternal anemia causes mental health issues in newborns. In one meta-analysis, among 20 studies of the association of maternal iron deficiency and newborn neurodevelopment, approximately half the studies reported that low maternal ferritin levels were associated with lower childhood performance on standardized tests of cognitive, motor, verbal, and memory function.¹⁹ Another systematic review concluded that the evidence linking maternal iron deficiency and child neurodevelopment is equivocal.²⁰

In a study of 532,232 nonadoptive children born in Sweden from 1987 to 2010, maternal anemia was associated with an increased risk of autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), and intellectual disability (ID).²¹ In Sweden maternal hemoglobin concentration is measured at 10, 25, and 37 weeks of gestation, permitting comparisons of anemia diagnosed early and late in pregnancy with neurodevelopmental outcomes. The association between anemia and neurodevelopmental disorders was greatest if anemia was diagnosed within the first 30 weeks of pregnancy. Compared with mothers without anemia, maternal anemia diagnosed within the first 30 weeks of pregnancy was associated with higher childhood rates of ASD (4.9% vs 3.5%), ADHD (9.3% vs 7.1%), and ID (3.1% vs 1.3%).²¹ The differences persisted in analyses that controlled for socioeconomic, maternal, and pregnancy-related factors. In a matched sibling comparison, the diagnosis of maternal anemia within the first 30 weeks of gestation was associated with an increased risk of ASD (OR, 2.25; 95% CI, 1.24-4.11) and ID (OR, 2.59; 95% CI, 1.08-6.22) but not ADHD.²¹ Other studies have also reported a relationship between maternal anemia and intellectual disability.^22,23

Measurement of hemoglobin will identify anemia, but hemoglobin measurement is not sufficiently sensitive to identify most cases of iron deficiency. Measuring ferritin can help to identify cases of iron deficiency before the onset of anemia, permitting early treatment of the nutrient deficiency. In pregnancy, iron deficiency is the prelude to developing anemia. Waiting until anemia occurs to diagnose and treat iron deficiency is suboptimal and may miss a critical window of fetal development that is dependent on maternal iron stores. During pregnancy, ferritin levels decrease as much as 80% between the first and third trimesters, as the fetus utilizes maternal iron stores for its growth.²⁴ We recommend the measurement of ferritin and hemoglobin at the first prenatal visit and again at 24 to 28 weeks’ gestation to optimize early detection and treatment of iron deficiency and reduce the frequency of anemia prior to birth. ●

During pregnancy, anemia and iron deficiency are prevalent because the fetus depletes maternal iron stores. Iron deficiency and iron deficiency anemia are not synonymous. Effective screening for iron deficiency in the first trimester of pregnancy requires the measurement of a sensitive and specific biomarker of iron deficiency, such as ferritin. Limiting the measurement of ferritin to the subset of patients with anemia will result in missing many cases of iron deficiency. By the time iron deficiency causes anemia, a severe deficiency is present. Detecting iron deficiency in pregnancy and promptly treating the deficiency will reduce the number of women with anemia in the third trimester and at birth.

Diagnosis of anemia

Anemia in pregnancy is diagnosed by a hemoglobin level and hematocrit concentration below 11 g/dL and 33%, respectively, in the first and third trimesters and below 10.5 g/dL and 32%, respectively, in the second trimester.¹ The prevalence of anemia in the first, second, and third trimesters is approximately 3%, 2%, and 11%, respectively.² At a hemoglobin concentration <11 g/dL, severe maternal morbidity rises significantly.³ The laboratory evaluation of pregnant women with anemia may require assessment of iron stores, measurement of folate and cobalamin (vitamin B12), and hemoglobin electrophoresis, if indicated.

Diagnosis of iron deficiency

Iron deficiency anemia is diagnosed by a ferritin level below 30 ng/mL.^4,5 Normal iron stores and iron insufficiency are indicated by ferritin levels 45 to 150 ng/mL and 30 to 44 ng/mL, respectively.^4,5 Ferritin is an acute phase reactant, and patients with inflammation or chronic illnesses may have iron deficiency and a normal ferritin level. For these patients, a transferrin saturation (TSAT) <16% would support a diagnosis of iron deficiency.⁶ TSAT is calculated from measurement of serum iron and total iron binding capacity. TSAT saturation may be elevated by iron supplements, which increase serum iron. If measurement of TSAT is necessary, interference with the measurement accuracy can be minimized by not taking an iron supplement on the day of testing.

Iron deficiency is present in approximately 50% of pregnant women.^7,8 The greatest prevalence of iron deficiency in pregnancy is observed in non-Hispanic Black females, followed by Hispanic females. Non-Hispanic White females had the lowest prevalence of iron deficiency.²

Fetal needs for iron often cause the depletion of maternal iron stores. Many pregnant women who have a normal ferritin level in the first trimester will develop iron deficiency in the third trimester, even with the usual recommended daily oral iron supplementation. We recommend measuring ferritin and hemoglobin at the first prenatal visit and again between 24 and 28 weeks’ gestation.

Impact of maternal anemia on maternal and newborn health

Iron plays a critical role in maternal health and fetal development independent of its role in red blood cell formation. Many proteins critical to maternal health and fetal development contain iron, including hemoglobin, myoglobin, cytochromes, ribonucleotide reductase, peroxidases, lipoxygenases, and cyclooxygenases. In the fetus, iron plays an important role in myelination of nerves, dendrite arborization, and synthesis of monoamine neurotransmitters.⁹

Many studies report that maternal anemia is associated with severe maternal morbidity and adverse newborn outcomes. The current literature must be interpreted with caution because socioeconomic factors influence iron stores. Iron deficiency and anemia is more common among economically and socially disadvantaged populations.^10-12 It is possible that repleting iron stores, alone, without addressing social determinants of health, including food and housing insecurity, may be insufficient to improve maternal and newborn health.

Maternal anemia is a risk factor for severe maternal morbidity and adverse newborn outcomes.^3,13-18 In a study of 515,270 live births in British Columbia between 2004 and 2016, maternal anemia was diagnosed in 12.8% of mothers.¹⁵ Maternal morbidity at birth was increased among patients with mild anemia (hemoglobin concentration of 9 to 10.9 g/dL), including higher rates of intrapartum transfusion (adjusted odds ratio [OR], 2.45; 95% confidence interval [CI], 1.74-3.45), cesarean birth (aOR, 1.17; 95% CI, 1.14-1.19), and chorioamnionitis (aOR, 1.35; 95% CI, 1.27-1.44). Newborn morbidity was also increased among newborns of mothers with mild anemia (hemoglobin concentrations of 9 to 10.9 g/dL), including birth before 37 weeks’ gestation (aOR, 1.09; 95% CI, 1.05-1.12), birth before 32 weeks’ gestation (aOR, 1.30; 95% CI, 1.21-1.39), admission to the intensive care unit (aOR, 1.21; 95% CI, 1.17-1.25), and respiratory distress syndrome (aOR, 1.35; 95% CI, 1.24-1.46).¹⁵ Adverse maternal and newborn outcomes were more prevalent among mothers with moderate (hemoglobin concentrations of 7 to 8.9 g/dL) or severe anemia (hemoglobin concentrations of <7 g/dL), compared with mild anemia. For example, compared with mothers with no anemia, mothers with moderate anemia had an increased risk of birth <37 weeks (aOR, 2.26) and birth <32 weeks (aOR, 3.95).¹⁵

In a study of 166,566 US pregnant patients, 6.1% were diagnosed with anemia.¹⁸ Patients with anemia were more likely to have antepartum thrombosis, preeclampsia, eclampsia, a cesarean birth, postpartum hemorrhage, a blood transfusion, and postpartum thrombosis.¹⁸ In this study, the newborns of mothers with anemia were more likely to have a diagnosis of antenatal or intrapartum fetal distress, a 5-minute Apgar score <7, and an admission to the neonatal intensive care unit.

Continue to: Maternal anemia and neurodevelopmental disorders in children...

Some experts, but not all, believe that iron deficiency during pregnancy may adversely impact fetal neurodevelopment and result in childhood behavior issues. All experts agree that more research is needed to understand if maternal anemia causes mental health issues in newborns. In one meta-analysis, among 20 studies of the association of maternal iron deficiency and newborn neurodevelopment, approximately half the studies reported that low maternal ferritin levels were associated with lower childhood performance on standardized tests of cognitive, motor, verbal, and memory function.¹⁹ Another systematic review concluded that the evidence linking maternal iron deficiency and child neurodevelopment is equivocal.²⁰

In a study of 532,232 nonadoptive children born in Sweden from 1987 to 2010, maternal anemia was associated with an increased risk of autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), and intellectual disability (ID).²¹ In Sweden maternal hemoglobin concentration is measured at 10, 25, and 37 weeks of gestation, permitting comparisons of anemia diagnosed early and late in pregnancy with neurodevelopmental outcomes. The association between anemia and neurodevelopmental disorders was greatest if anemia was diagnosed within the first 30 weeks of pregnancy. Compared with mothers without anemia, maternal anemia diagnosed within the first 30 weeks of pregnancy was associated with higher childhood rates of ASD (4.9% vs 3.5%), ADHD (9.3% vs 7.1%), and ID (3.1% vs 1.3%).²¹ The differences persisted in analyses that controlled for socioeconomic, maternal, and pregnancy-related factors. In a matched sibling comparison, the diagnosis of maternal anemia within the first 30 weeks of gestation was associated with an increased risk of ASD (OR, 2.25; 95% CI, 1.24-4.11) and ID (OR, 2.59; 95% CI, 1.08-6.22) but not ADHD.²¹ Other studies have also reported a relationship between maternal anemia and intellectual disability.^22,23

Measurement of hemoglobin will identify anemia, but hemoglobin measurement is not sufficiently sensitive to identify most cases of iron deficiency. Measuring ferritin can help to identify cases of iron deficiency before the onset of anemia, permitting early treatment of the nutrient deficiency. In pregnancy, iron deficiency is the prelude to developing anemia. Waiting until anemia occurs to diagnose and treat iron deficiency is suboptimal and may miss a critical window of fetal development that is dependent on maternal iron stores. During pregnancy, ferritin levels decrease as much as 80% between the first and third trimesters, as the fetus utilizes maternal iron stores for its growth.²⁴ We recommend the measurement of ferritin and hemoglobin at the first prenatal visit and again at 24 to 28 weeks’ gestation to optimize early detection and treatment of iron deficiency and reduce the frequency of anemia prior to birth. ●

During pregnancy, anemia and iron deficiency are prevalent because the fetus depletes maternal iron stores. Iron deficiency and iron deficiency anemia are not synonymous. Effective screening for iron deficiency in the first trimester of pregnancy requires the measurement of a sensitive and specific biomarker of iron deficiency, such as ferritin. Limiting the measurement of ferritin to the subset of patients with anemia will result in missing many cases of iron deficiency. By the time iron deficiency causes anemia, a severe deficiency is present. Detecting iron deficiency in pregnancy and promptly treating the deficiency will reduce the number of women with anemia in the third trimester and at birth.

Diagnosis of anemia

Anemia in pregnancy is diagnosed by a hemoglobin level and hematocrit concentration below 11 g/dL and 33%, respectively, in the first and third trimesters and below 10.5 g/dL and 32%, respectively, in the second trimester.¹ The prevalence of anemia in the first, second, and third trimesters is approximately 3%, 2%, and 11%, respectively.² At a hemoglobin concentration <11 g/dL, severe maternal morbidity rises significantly.³ The laboratory evaluation of pregnant women with anemia may require assessment of iron stores, measurement of folate and cobalamin (vitamin B12), and hemoglobin electrophoresis, if indicated.

Diagnosis of iron deficiency

Iron deficiency anemia is diagnosed by a ferritin level below 30 ng/mL.^4,5 Normal iron stores and iron insufficiency are indicated by ferritin levels 45 to 150 ng/mL and 30 to 44 ng/mL, respectively.^4,5 Ferritin is an acute phase reactant, and patients with inflammation or chronic illnesses may have iron deficiency and a normal ferritin level. For these patients, a transferrin saturation (TSAT) <16% would support a diagnosis of iron deficiency.⁶ TSAT is calculated from measurement of serum iron and total iron binding capacity. TSAT saturation may be elevated by iron supplements, which increase serum iron. If measurement of TSAT is necessary, interference with the measurement accuracy can be minimized by not taking an iron supplement on the day of testing.

Iron deficiency is present in approximately 50% of pregnant women.^7,8 The greatest prevalence of iron deficiency in pregnancy is observed in non-Hispanic Black females, followed by Hispanic females. Non-Hispanic White females had the lowest prevalence of iron deficiency.²

Fetal needs for iron often cause the depletion of maternal iron stores. Many pregnant women who have a normal ferritin level in the first trimester will develop iron deficiency in the third trimester, even with the usual recommended daily oral iron supplementation. We recommend measuring ferritin and hemoglobin at the first prenatal visit and again between 24 and 28 weeks’ gestation.

Impact of maternal anemia on maternal and newborn health

Iron plays a critical role in maternal health and fetal development independent of its role in red blood cell formation. Many proteins critical to maternal health and fetal development contain iron, including hemoglobin, myoglobin, cytochromes, ribonucleotide reductase, peroxidases, lipoxygenases, and cyclooxygenases. In the fetus, iron plays an important role in myelination of nerves, dendrite arborization, and synthesis of monoamine neurotransmitters.⁹

Many studies report that maternal anemia is associated with severe maternal morbidity and adverse newborn outcomes. The current literature must be interpreted with caution because socioeconomic factors influence iron stores. Iron deficiency and anemia is more common among economically and socially disadvantaged populations.^10-12 It is possible that repleting iron stores, alone, without addressing social determinants of health, including food and housing insecurity, may be insufficient to improve maternal and newborn health.

Maternal anemia is a risk factor for severe maternal morbidity and adverse newborn outcomes.^3,13-18 In a study of 515,270 live births in British Columbia between 2004 and 2016, maternal anemia was diagnosed in 12.8% of mothers.¹⁵ Maternal morbidity at birth was increased among patients with mild anemia (hemoglobin concentration of 9 to 10.9 g/dL), including higher rates of intrapartum transfusion (adjusted odds ratio [OR], 2.45; 95% confidence interval [CI], 1.74-3.45), cesarean birth (aOR, 1.17; 95% CI, 1.14-1.19), and chorioamnionitis (aOR, 1.35; 95% CI, 1.27-1.44). Newborn morbidity was also increased among newborns of mothers with mild anemia (hemoglobin concentrations of 9 to 10.9 g/dL), including birth before 37 weeks’ gestation (aOR, 1.09; 95% CI, 1.05-1.12), birth before 32 weeks’ gestation (aOR, 1.30; 95% CI, 1.21-1.39), admission to the intensive care unit (aOR, 1.21; 95% CI, 1.17-1.25), and respiratory distress syndrome (aOR, 1.35; 95% CI, 1.24-1.46).¹⁵ Adverse maternal and newborn outcomes were more prevalent among mothers with moderate (hemoglobin concentrations of 7 to 8.9 g/dL) or severe anemia (hemoglobin concentrations of <7 g/dL), compared with mild anemia. For example, compared with mothers with no anemia, mothers with moderate anemia had an increased risk of birth <37 weeks (aOR, 2.26) and birth <32 weeks (aOR, 3.95).¹⁵

In a study of 166,566 US pregnant patients, 6.1% were diagnosed with anemia.¹⁸ Patients with anemia were more likely to have antepartum thrombosis, preeclampsia, eclampsia, a cesarean birth, postpartum hemorrhage, a blood transfusion, and postpartum thrombosis.¹⁸ In this study, the newborns of mothers with anemia were more likely to have a diagnosis of antenatal or intrapartum fetal distress, a 5-minute Apgar score <7, and an admission to the neonatal intensive care unit.

Continue to: Maternal anemia and neurodevelopmental disorders in children...

Some experts, but not all, believe that iron deficiency during pregnancy may adversely impact fetal neurodevelopment and result in childhood behavior issues. All experts agree that more research is needed to understand if maternal anemia causes mental health issues in newborns. In one meta-analysis, among 20 studies of the association of maternal iron deficiency and newborn neurodevelopment, approximately half the studies reported that low maternal ferritin levels were associated with lower childhood performance on standardized tests of cognitive, motor, verbal, and memory function.¹⁹ Another systematic review concluded that the evidence linking maternal iron deficiency and child neurodevelopment is equivocal.²⁰

In a study of 532,232 nonadoptive children born in Sweden from 1987 to 2010, maternal anemia was associated with an increased risk of autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), and intellectual disability (ID).²¹ In Sweden maternal hemoglobin concentration is measured at 10, 25, and 37 weeks of gestation, permitting comparisons of anemia diagnosed early and late in pregnancy with neurodevelopmental outcomes. The association between anemia and neurodevelopmental disorders was greatest if anemia was diagnosed within the first 30 weeks of pregnancy. Compared with mothers without anemia, maternal anemia diagnosed within the first 30 weeks of pregnancy was associated with higher childhood rates of ASD (4.9% vs 3.5%), ADHD (9.3% vs 7.1%), and ID (3.1% vs 1.3%).²¹ The differences persisted in analyses that controlled for socioeconomic, maternal, and pregnancy-related factors. In a matched sibling comparison, the diagnosis of maternal anemia within the first 30 weeks of gestation was associated with an increased risk of ASD (OR, 2.25; 95% CI, 1.24-4.11) and ID (OR, 2.59; 95% CI, 1.08-6.22) but not ADHD.²¹ Other studies have also reported a relationship between maternal anemia and intellectual disability.^22,23

Measurement of hemoglobin will identify anemia, but hemoglobin measurement is not sufficiently sensitive to identify most cases of iron deficiency. Measuring ferritin can help to identify cases of iron deficiency before the onset of anemia, permitting early treatment of the nutrient deficiency. In pregnancy, iron deficiency is the prelude to developing anemia. Waiting until anemia occurs to diagnose and treat iron deficiency is suboptimal and may miss a critical window of fetal development that is dependent on maternal iron stores. During pregnancy, ferritin levels decrease as much as 80% between the first and third trimesters, as the fetus utilizes maternal iron stores for its growth.²⁴ We recommend the measurement of ferritin and hemoglobin at the first prenatal visit and again at 24 to 28 weeks’ gestation to optimize early detection and treatment of iron deficiency and reduce the frequency of anemia prior to birth. ●

As a regular viewer of Jeopardy! I find it both interesting and educational. But the psychiatric neuroscientist in me marvels at the splendid cerebral attributes embedded in the brains of Jeopardy! champions.

Back in my college days, I participated in what were then called “general knowledge contests” and won a couple of trophies, the most gratifying of which was when our team of medical students beat the faculty team! Later, when my wife and I had children, Trivial Pursuit was a game frequently played in our household. So it is no wonder I have often thought of the remarkable, sometimes stunning intellectual performances of Jeopardy! champions.

What does it take to excel at Jeopardy!?

Watching contestants successfully answer a bewildering array of questions across an extensive spectrum of topics is simply dazzling and prompts me to ask: Which neurologic structures play a central role in the brains of Jeopardy! champions? So I channeled my inner neurobiologist and came up with the following prerequisites to excel at Jeopardy!:

• A hippocampus on steroids! Memory is obviously a core ingredient for responding to Jeopardy! questions. Unlike ordinary mortals, Jeopardy! champions appear to retain and instantaneously, accurately recall everything they have read, saw, or heard.
• A sublime network of dendritic spines, where learning is immediately transduced to biological memories, thanks to the wonders of experiential neuroplasticity in homo sapiens.
• A superlative frontal lobe, which provides the champion with an ultra-rapid abstraction ability in the dorsolateral prefrontal cortex, along with razor-sharp concentration and attention.
• An extremely well-myelinated network of the 137,000 miles of white mat­ter fibers in the human brain. This is what leads to fabulous processing speed. Rapid neurotransmission is impossible without very well-myelinated axons and dendrites. It is not enough for a Jeopardy! champion to know the answer and retrieve it from the hippocampus—they also must transmit the answer at lightning speed to the speech area, and then activate the motor area to enunciate the answer. Processing speed is the foundation of overall cognitive functioning.
• A first-rate Broca’s area, referred to as “the brain’s scriptwriter,” which shapes human speech. It receives the flow of sensory information from the temporal cortex, devises a plan for speaking, and passes that plan seamlessly to the motor cortex, which controls the movements of the mouth.
• Blistering speed reflexes to click the handheld response buzzer within a fraction of a millisecond after the host finishes reading the clue (not before, or a penalty is incurred). Jeopardy! champions always click the buzzer faster than their competitors, who may know the answer but have ordinary motor reflexes (also related to the degree of myelination and a motoric component of processing speed).
• A thick corpus callosum, the largest interhemispheric commissure, a bundle of 200 million white matter fibers connecting analogous regions in the right and left hemispheres, is vital for the rapid bidirectional transfer of bits of information from the intuitive/nonverbal right hemisphere to the mathematical/verbal left hemisphere, when the answer requires right hemispheric input.
• A bright occipital cortex and exceptional optic nerve and retina, so that champions can recognize faces or locations and read the questions before the host finishes reading them, which gives them an awesome edge on other contestants.

Obviously, the brains of Jeopardy! champions are a breed of their own, with exceptional performances by multiple regions converging to produce a winning performance. But during their childhood and youthful years, such brains also generate motivation, curiosity, and interest in a wide range of topics, from cultures, regions, music genres, and word games to history, geography, sports, science, medicine, astronomy, and Greek mythology.

Jeopardy! champions may appear to have regular jobs and ordinary lives, but they have resplendent “renaissance” brains. I wonder how they spent their childhood, who mentored them, what type of family lives they had, and what they dream of accomplishing other than winning on Jeopardy!. Will their awe-inspiring performance in Jeopardy! translate to overall success in life? That’s a story that remains to be told.

As a regular viewer of Jeopardy! I find it both interesting and educational. But the psychiatric neuroscientist in me marvels at the splendid cerebral attributes embedded in the brains of Jeopardy! champions.

Back in my college days, I participated in what were then called “general knowledge contests” and won a couple of trophies, the most gratifying of which was when our team of medical students beat the faculty team! Later, when my wife and I had children, Trivial Pursuit was a game frequently played in our household. So it is no wonder I have often thought of the remarkable, sometimes stunning intellectual performances of Jeopardy! champions.

What does it take to excel at Jeopardy!?

Watching contestants successfully answer a bewildering array of questions across an extensive spectrum of topics is simply dazzling and prompts me to ask: Which neurologic structures play a central role in the brains of Jeopardy! champions? So I channeled my inner neurobiologist and came up with the following prerequisites to excel at Jeopardy!:

• A hippocampus on steroids! Memory is obviously a core ingredient for responding to Jeopardy! questions. Unlike ordinary mortals, Jeopardy! champions appear to retain and instantaneously, accurately recall everything they have read, saw, or heard.
• A sublime network of dendritic spines, where learning is immediately transduced to biological memories, thanks to the wonders of experiential neuroplasticity in homo sapiens.
• A superlative frontal lobe, which provides the champion with an ultra-rapid abstraction ability in the dorsolateral prefrontal cortex, along with razor-sharp concentration and attention.
• An extremely well-myelinated network of the 137,000 miles of white mat­ter fibers in the human brain. This is what leads to fabulous processing speed. Rapid neurotransmission is impossible without very well-myelinated axons and dendrites. It is not enough for a Jeopardy! champion to know the answer and retrieve it from the hippocampus—they also must transmit the answer at lightning speed to the speech area, and then activate the motor area to enunciate the answer. Processing speed is the foundation of overall cognitive functioning.
• A first-rate Broca’s area, referred to as “the brain’s scriptwriter,” which shapes human speech. It receives the flow of sensory information from the temporal cortex, devises a plan for speaking, and passes that plan seamlessly to the motor cortex, which controls the movements of the mouth.
• Blistering speed reflexes to click the handheld response buzzer within a fraction of a millisecond after the host finishes reading the clue (not before, or a penalty is incurred). Jeopardy! champions always click the buzzer faster than their competitors, who may know the answer but have ordinary motor reflexes (also related to the degree of myelination and a motoric component of processing speed).
• A thick corpus callosum, the largest interhemispheric commissure, a bundle of 200 million white matter fibers connecting analogous regions in the right and left hemispheres, is vital for the rapid bidirectional transfer of bits of information from the intuitive/nonverbal right hemisphere to the mathematical/verbal left hemisphere, when the answer requires right hemispheric input.
• A bright occipital cortex and exceptional optic nerve and retina, so that champions can recognize faces or locations and read the questions before the host finishes reading them, which gives them an awesome edge on other contestants.

Obviously, the brains of Jeopardy! champions are a breed of their own, with exceptional performances by multiple regions converging to produce a winning performance. But during their childhood and youthful years, such brains also generate motivation, curiosity, and interest in a wide range of topics, from cultures, regions, music genres, and word games to history, geography, sports, science, medicine, astronomy, and Greek mythology.

Jeopardy! champions may appear to have regular jobs and ordinary lives, but they have resplendent “renaissance” brains. I wonder how they spent their childhood, who mentored them, what type of family lives they had, and what they dream of accomplishing other than winning on Jeopardy!. Will their awe-inspiring performance in Jeopardy! translate to overall success in life? That’s a story that remains to be told.

As a regular viewer of Jeopardy! I find it both interesting and educational. But the psychiatric neuroscientist in me marvels at the splendid cerebral attributes embedded in the brains of Jeopardy! champions.

Back in my college days, I participated in what were then called “general knowledge contests” and won a couple of trophies, the most gratifying of which was when our team of medical students beat the faculty team! Later, when my wife and I had children, Trivial Pursuit was a game frequently played in our household. So it is no wonder I have often thought of the remarkable, sometimes stunning intellectual performances of Jeopardy! champions.

What does it take to excel at Jeopardy!?

Watching contestants successfully answer a bewildering array of questions across an extensive spectrum of topics is simply dazzling and prompts me to ask: Which neurologic structures play a central role in the brains of Jeopardy! champions? So I channeled my inner neurobiologist and came up with the following prerequisites to excel at Jeopardy!:

• A hippocampus on steroids! Memory is obviously a core ingredient for responding to Jeopardy! questions. Unlike ordinary mortals, Jeopardy! champions appear to retain and instantaneously, accurately recall everything they have read, saw, or heard.
• A sublime network of dendritic spines, where learning is immediately transduced to biological memories, thanks to the wonders of experiential neuroplasticity in homo sapiens.
• A superlative frontal lobe, which provides the champion with an ultra-rapid abstraction ability in the dorsolateral prefrontal cortex, along with razor-sharp concentration and attention.
• An extremely well-myelinated network of the 137,000 miles of white mat­ter fibers in the human brain. This is what leads to fabulous processing speed. Rapid neurotransmission is impossible without very well-myelinated axons and dendrites. It is not enough for a Jeopardy! champion to know the answer and retrieve it from the hippocampus—they also must transmit the answer at lightning speed to the speech area, and then activate the motor area to enunciate the answer. Processing speed is the foundation of overall cognitive functioning.
• A first-rate Broca’s area, referred to as “the brain’s scriptwriter,” which shapes human speech. It receives the flow of sensory information from the temporal cortex, devises a plan for speaking, and passes that plan seamlessly to the motor cortex, which controls the movements of the mouth.
• Blistering speed reflexes to click the handheld response buzzer within a fraction of a millisecond after the host finishes reading the clue (not before, or a penalty is incurred). Jeopardy! champions always click the buzzer faster than their competitors, who may know the answer but have ordinary motor reflexes (also related to the degree of myelination and a motoric component of processing speed).
• A thick corpus callosum, the largest interhemispheric commissure, a bundle of 200 million white matter fibers connecting analogous regions in the right and left hemispheres, is vital for the rapid bidirectional transfer of bits of information from the intuitive/nonverbal right hemisphere to the mathematical/verbal left hemisphere, when the answer requires right hemispheric input.
• A bright occipital cortex and exceptional optic nerve and retina, so that champions can recognize faces or locations and read the questions before the host finishes reading them, which gives them an awesome edge on other contestants.

Obviously, the brains of Jeopardy! champions are a breed of their own, with exceptional performances by multiple regions converging to produce a winning performance. But during their childhood and youthful years, such brains also generate motivation, curiosity, and interest in a wide range of topics, from cultures, regions, music genres, and word games to history, geography, sports, science, medicine, astronomy, and Greek mythology.

Jeopardy! champions may appear to have regular jobs and ordinary lives, but they have resplendent “renaissance” brains. I wonder how they spent their childhood, who mentored them, what type of family lives they had, and what they dream of accomplishing other than winning on Jeopardy!. Will their awe-inspiring performance in Jeopardy! translate to overall success in life? That’s a story that remains to be told.

The medicated intrauterine devices (IUDs), including the levonorgestrel-releasing IUD (LNG-IUD) (Mirena, Kyleena, Skyla, and Liletta) and the copper IUD (Cu-IUD; Paragard), are remarkably effective contraceptives. For the 52-mg LNG-IUD (Mirena, Liletta) the pregnancy rate over 6 years of use averaged less than 0.2% per year.^1,2 For the Cu-IUD, the pregnancy rate over 10 years of use averaged 0.5% per year for the first 3 years of use and 0.2% per year over the following 7 years of use.³ IUD perforation of the uterus, expulsion, and malposition are recognized complications of IUD use. Our understanding of the prevalence and management of malpositioned IUDs is evolving and the main focus of this editorial.

Complete and partial uterus perforation

A complete uterine perforation occurs when the entire IUD is outside the walls of the uterus. A partial uterine perforation occurs when the IUD is outside the uterine cavity, but a portion of the IUD remains in the myometrium. When uterine perforation is suspected, ultrasound can determine if the IUD is properly sited within the uterus. If ultrasonography does not detect the IUD within the uterus, an x-ray of the pelvis and abdomen should be obtained to determine if the IUD is in the peritoneal cavity. If both an ultrasound and a pelvic-abdominal x-ray do not detect the IUD, the IUD was probably expelled from the patient.

Uterine perforation is uncommon and occurs once in every 500 to 1,000 insertions in non-breastfeeding women.^4-8 The most common symptoms reported by patients with a perforated IUD are pain and/or bleeding.⁸ Investigators in the European Active Surveillance Study on Intrauterine Devices (EURAS) enrolled more than 60,000 patients who had an IUD insertion and followed them for 12 months with more than 39,000 followed for up to 60 months.^7,8 The uterine perforation rate per 1,000 IUD insertions in non-breastfeeding women with 60 months of follow-up was 1.6 for the LNG-IUD and 0.8 for the Cu-IUD.⁸ The rate of uterine perforation was much higher in women who are breastfeeding or recently postpartum. In the EURAS study after 60 months of follow-up, the perforation rate per 1,000 insertions among breastfeeding women was 7.9 for the LNG-IUS and 4.7 for the Cu-IUD.⁸

Remarkably very few IUD perforations were detected at the time of insertion, including only 2% of the LNG-IUD insertions and 17% of the Cu-IUD insertions.⁸ Many perforations were not detected until more than 12 months following insertion, including 32% of the LNG-IUD insertions and 22% of the Cu-IUD insertions.⁸ Obviously, an IUD that has completely perforated the uterus and resides in the peritoneal cavity is not an effective contraceptive. For some patients, the IUD perforation was initially diagnosed after they became pregnant, and imaging studies to locate the IUD and assess the pregnancy were initiated. Complete perforation is usually treated with laparoscopy to remove the IUD and reduce the risk of injury to intra-abdominal organs.

Patients with an IUD partial perforation may present with pelvic pain or abnormal uterine bleeding.⁹ An ultrasound study to explore the cause of the presenting symptom may detect the partial perforation. It is estimated that approximately 20% of cases of IUD perforation are partial perforation.⁹ Over time, a partial perforation may progress to a complete perforation. In some cases of partial perforation, the IUD string may still be visible in the cervix, and the IUD may be removed by pulling on the strings.⁸ Hysteroscopy and/or laparoscopy may be needed to remove a partially perforated IUD. Following a partial or complete IUD perforation, if the patient desires to continue with IUD contraception, it would be wise to insert a new IUD under ultrasound guidance or assess proper placement with a postplacement ultrasound.

Continue to: Expulsion...

IUD expulsion occurs in approximately 3% to 11% of patients.^10-13 The age of the patient influences the rate of expulsion. In a study of 2,748 patients with a Cu-IUD, the rate of expulsion by age for patients <20 years, 20–24 years, 25–29 years, 30–34 years, and ≥35 years was 8.2%, 3.2%, 3.0%, 2.3%, and 1.8%, respectively.¹⁰ In this study, age did not influence the rate of IUD removal for pelvic pain or abnormal bleeding, which was 4% to 5% across all age groups.¹⁰ In a study of 5,403 patients with an IUD, the rate of IUD expulsion by age for patients <20 years, 20–29 years, and 30–45 years was 14.6%, 7.3%, and 7.2%, respectively.¹² In this study, the 3-year cumulative rate of expulsion was 10.2%.¹² There was no statistically significant difference in the 3-year cumulative rate of expulsion for the 52-mg LNG-IUD (10.1%) and Cu-IUD (10.7%).¹²

The majority of patients who have an IUD expulsion recognize the event and seek additional contraception care. A few patients first recognize the IUD expulsion when they become pregnant, and imaging studies detect no IUD in the uterus or the peritoneal cavity. In a study of more than 17,000 patients using an LNG-IUD, 108 pregnancies were reported. Seven pregnancies occurred in patients who did not realize their IUD was expelled.¹⁴ Patients who have had an IUD expulsion and receive a new IUD are at increased risk for re-expulsion. For these patients, reinsertion of an IUD could be performed under ultrasound guidance to ensure and document optimal initial IUD position within the uterus, or ultrasound can be obtained postinsertion to document appropriate IUD position.

Malposition—prevalence and management

Our understanding of the prevalence and management of a malpositioned IUD is evolving. For the purposes of this discussion a malpositioned IUD is defined as being in the uterus, but not properly positioned within the uterine cavity. Perforation into the peritoneal cavity and complete expulsion of an IUD are considered separate entities. However, a malpositioned IUD within the uterus may eventually perforate the uterus or be expelled from the body. For example, an IUD embedded in the uterine wall may eventually work its way through the wall and become perforated, residing in the peritoneal cavity. An IUD with the stem in the cervix below the internal os may eventually be expelled from the uterus and leave the body through the vagina.

High-quality ultrasonography, including 2-dimensional (2-D) ultrasound with videoclips or 3-dimensional (3-D) ultrasound with coronal views, has greatly advanced our understanding of the prevalence and characteristics of a malpositioned IUD.^15-18 Ultrasound features of an IUD correctly placed within the uterus include:

• the IUD is in the uterus
• the shaft is in the midline of the uterine cavity
• the shaft of the IUD is not in the endocervix
• the IUD arms are at a 90-degree angle from the shaft
• the top of the IUD is within 2 cm of the fundus
• the IUD is not rotated outside of the cornual plane, inverted or transverse.

Ultrasound imaging has identified multiple types of malpositioned IUDs, including:

• IUD embedded in the myometrium—a portion of the IUD is embedded in the uterine wall
• low-lying IUD—the IUD is low in the uterine cavity but not in the endocervix
• IUD in the endocervix—the stem is in the endocervical canal
• rotated—the IUD is rotated outside the cornual plane
• malpositioned arms—the arms are not at a 90-degree angle to the stem
• the IUD is inverted, transverse, or laterally displaced.

IUD malposition is highly prevalent and has been identified in 10% to 20% of convenience cohorts in which an ultrasound study was performed.^15-18

Benacerraf, Shipp, and Bromley were among the first experts to use ultrasound to detect the high prevalence of malpositioned IUDs among a convenience sample of 167 patients with an IUD undergoing ultrasound for a variety of indications. Using 3-D ultrasound, including reconstructed coronal views, they identified 28 patients (17%) with a malpositioned IUD based on the detection of the IUD “poking into the substance of the uterus or cervix.” Among the patients with a malpositioned IUD, the principal indication for the ultrasound study was pelvic pain (39%) or abnormal uterine bleeding (36%). Among women with a normally sited IUD, pelvic pain (19%) or abnormal uterine bleeding (15%) were less often the principal indication for the ultrasound.¹⁵ The malpositioned IUD was removed in 21 of the 28 cases and the symptoms of pelvic pain or abnormal bleeding resolved in 20 of the 21 patients.¹⁵

Other investigators have confirmed the observation that IUD malposition is common.^16-18 In a retrospective study of 1,748 pelvic ultrasounds performed for any indication where an IUD was present, after excluding 13 patients who were determined to have expelled their IUD (13) and 13 patients with a perforated IUD, 156 patients (8.9%) were diagnosed as having a malpositioned IUD.¹⁶ IUD malposition was diagnosed when the IUD was in the uterus but positioned in the lower uterine segment, cervix, rotated or embedded in the uterus. An IUD in the lower uterine segment or cervix was detected in 133 patients, representing 85% of cases. Among these cases, 29 IUDs were also embedded and/or rotated, indicating that some IUDs have multiple causes of the malposition. Twenty-one IUDs were near the fundus but embedded and/or rotated. Controls with a normally-sited IUD were selected for comparison to the case group. Among IUD users, the identification of suspected adenomyosis on the ultrasound was associated with an increased risk of IUD malposition (odds ratio [OR], 3.04; 95% confidence interval [CI], 1.08-8.52).¹⁶ In this study, removal of a malpositioned LNG-IUD, without initiating a highly reliable contraceptive was associated with an increased risk of pregnancy. It is important to initiate a highly reliable form of contraception if the plan is to remove a malpositioned IUD.^16,19

In a study of 1,253 pelvic ultrasounds performed for any indication where an IUD was identified in the uterus, 263 IUDs (19%) were determined to be malpositioned.¹⁷ In this study the location of the malpositioned IUDs included¹⁷:

• the lower uterine segment not extending into the cervix (38%)
• in the lower uterine segment extending into the cervix (22%)
• in the cervix (26%)
• rotated axis of the IUD (12%)
• other (2%).

Among the 236 malpositioned IUDs, 24% appeared to be embedded in the uterine wall.¹⁷ Compared with patients with a normally-sited IUD on ultrasound, patients with a malpositioned IUD more frequently reported vaginal bleeding (30% vs 19%; P<.005) and pelvic pain (43% vs 30%; P<.002), similar to the findings in the Benacerraf et al. study.¹⁴

Connolly and Fox¹⁸ designed an innovative study to determine the rate of malpositioned IUDs using 2-D ultrasound to ensure proper IUD placement at the time of insertion with a follow-up 3-D ultrasound 8 weeks after insertion to assess IUD position within the uterus. At the 8-week 3-D ultrasound, among 763 women, 16.6% of the IUDs were malpositioned.¹⁸ In this study, IUD position was determined to be correct if all the following features were identified:

• the IUD shaft was in the midline of the uterine cavity
• the IUD arms were at 90 degrees from the stem
• the top of the IUD was within 3 to 4 mm of the fundus
• the IUD was not rotated, inverted or transverse.

IUD malpositions were categorized as:

• embedded in the uterine wall
• low in the uterine cavity
• in the endocervical canal
• misaligned
• perforated
• expulsed.

At the 8-week follow-up, 636 patients (83.4%) had an IUD that was correctly positioned.¹⁸ In 127 patients (16.6%) IUD malposition was identified, with some patients having more than one type of malposition. The types of malposition identified were:

• embedded in the myometrium (54%)
• misaligned, including rotated, laterally displaced, inverted, transverse or arms not deployed (47%)
• low in the uterine cavity (39%)
• in the endocervical canal (14%)
• perforated (3%)
• expulsion (0%).

Recall that all of these patients had a 2-D ultrasound at the time of insertion that identified the IUD as correctly placed. This suggests that during the 8 weeks following IUD placement there were changes in the location of the IUD or that 2-D ultrasound has lower sensitivity than 3-D ultrasound to detect malposition. Of note, at the 8-week follow-up, bleeding or pain was reported by 36% of the patients with a malpositioned IUD and 20% of patients with a correctly positioned IUD.¹⁷ Sixty-seven of the 127 malpositioned IUDs “required” removal, but the precise reasons for the removals were not delineated. The investigators concluded that 3-D ultrasonography is useful for the detection of IUD malposition and could be considered as part of ongoing IUD care, if symptoms of pain or bleeding occur.¹⁸

Continue to: IUD malposition following postplacental insertion...

IUD malposition following postplacental insertion

IUD malposition is common in patients who have had a postplacental insertion. Ultrasound imaging plays an important role in detecting IUD expulsion and malposition in these cases. Postplacental IUD insertion is defined as the placement of an IUD within 10 minutes following delivery of the placenta. Postplacental IUD insertion can be performed following a vaginal or cesarean birth and with a Cu-IUD or LNG-IUD. The good news is that postplacental IUD insertion reduces the risk of unplanned pregnancy in the years following birth. However, postplacental IUD insertion is associated with a high rate of IUD malposition.

In a study of 162 patients who had postplacental insertion of a Cu-IUD following a vaginal birth, ultrasound and physical examination at 6 months demonstrated complete IUD expulsion in 8%, partial expulsion in 16%, and malposition in 15%.²⁰ The IUD was correctly sited in 56% of patients. Seven patients (4%) had the IUD removed, and 1 patient had a perforated IUD. Among the 25 malpositioned IUDs, 14 were not within 1 cm of the fundus, and 11 were rotated outside of the axis of the cornuas. In this study partial expulsion was defined as an IUD protruding from the external cervical os on physical exam or demonstration of the distal tip of the IUD below the internal os of the cervix on ultrasound. Malposition was defined as an IUD that was >1 cm from the fundus or in an abnormal location or axis, but not partially expelled.

In a study of 69 patients who had postplacental insertion of a Cu-IUD following a cesarean birth, ultrasound and physical examination at 6 months demonstrated complete IUD expulsion in 3%, partial expulsion (stem in the cervix below the internal os) in 4% and malposition in 30%.²⁰ The IUD was correctly positioned in 59% of the patients.²¹ The IUD had been electively removed in 3%. Among the 21 patients with a malpositioned IUD, 10 were rotated within the uterine cavity, 6 were inverted (upside down), 3 were low-lying, and 2 were transverse.²¹ Given the relatively high rate of IUD malposition following postplacental insertion, it may be useful to perform a pelvic ultrasound at a postpartum visit to assess the location of the IUD, if ultrasonography is available.

Management of the malpositioned IUD

There are no consensus guidelines on how to care for a patient with a malpositioned IUD. Clinicians need to use their best judgment and engage the patient in joint decision making when managing a malpositioned IUD. When an IUD is malpositioned and the patient has bothersome symptoms of pelvic pain or abnormal bleeding that have not responded to standard interventions, consideration may be given to a remove and replace strategy. When the stem of the IUD is below the level of the internal os on ultrasound or visible at the external os on physical examination, consideration should be given to removing and replacing the IUD. However, if the IUD is removed without replacement or the initiation of a highly reliable contraceptive, the risk of unplanned pregnancy is considerable.^16,19

IUD totally or partially within the cervix or low-lying. When an IUD is in the cervix, the contraceptive efficacy of the IUD may be diminished, especially with a Cu-IUD.²² In these cases, removing and replacing the IUD is an option. In a survey of 20 expert clinicians, >80% recommended replacing an IUD that was totally or partially in the cervical canal.²³ But most of the experts would not replace an IUD that was incidentally noted on ultrasound to be low-lying, being positioned more than 2 cm below the fundus, with no portion of the IUD in the cervical canal. In the same survey, for patients with a low-lying IUD and pelvic pain or bleeding, the majority of experts reported that they would explore other causes of bleeding and pelvic pain not related to the IUD itself and not replace the IUD, but 30% of the experts reported that they would remove and replace the device.²³

IUD embedded in the myometrium with pelvic pain. Based on my clinical experience, when a patient has persistent pelvic pain following the insertion of an IUD and the pain does not resolve with standard measures including medication, an ultrasound study is warranted to assess the position of the IUD. If the ultrasound demonstrates that an arm of the IUD is embedded in the myometrium, removal of the IUD may be associated with resolution of the pain. Reinsertion of an IUD under ultrasound guidance may result in a correctly-sited IUD with no recurrence of pelvic pain.

IUD rotated within the uterus with no pain or abnormal bleeding. For an IUD that is near the fundus and rotated on its axis within the uterus, if the patient has no symptoms of pain or abnormal bleeding, my recommendation to the patient would be to leave the device in situ.

Without available guidelines, engage in clinician-patient discussion

It is clear that IUD malposition is common, occurring in 10% to 20% of patients with an IUD. High-quality ultrasound imaging is helpful in detecting IUD malposition, including 2-D ultrasound with videoclips and/or 3-D ultrasound with coronal reconstruction. More data are needed to identify the best options for managing various types of malpositioned IUDs in patients with and without bothersome symptoms such as pain and bleeding. Until consensus guidelines are developed, clinicians need to engage the patient in a discussion of how to best manage the malpositioned IUD. Medicated IUDs and progestin subdermal implants are our two most effective reversible contraceptives. They are among the most important advances in health care over the past half-century. ●

The medicated intrauterine devices (IUDs), including the levonorgestrel-releasing IUD (LNG-IUD) (Mirena, Kyleena, Skyla, and Liletta) and the copper IUD (Cu-IUD; Paragard), are remarkably effective contraceptives. For the 52-mg LNG-IUD (Mirena, Liletta) the pregnancy rate over 6 years of use averaged less than 0.2% per year.^1,2 For the Cu-IUD, the pregnancy rate over 10 years of use averaged 0.5% per year for the first 3 years of use and 0.2% per year over the following 7 years of use.³ IUD perforation of the uterus, expulsion, and malposition are recognized complications of IUD use. Our understanding of the prevalence and management of malpositioned IUDs is evolving and the main focus of this editorial.

Complete and partial uterus perforation

A complete uterine perforation occurs when the entire IUD is outside the walls of the uterus. A partial uterine perforation occurs when the IUD is outside the uterine cavity, but a portion of the IUD remains in the myometrium. When uterine perforation is suspected, ultrasound can determine if the IUD is properly sited within the uterus. If ultrasonography does not detect the IUD within the uterus, an x-ray of the pelvis and abdomen should be obtained to determine if the IUD is in the peritoneal cavity. If both an ultrasound and a pelvic-abdominal x-ray do not detect the IUD, the IUD was probably expelled from the patient.

Uterine perforation is uncommon and occurs once in every 500 to 1,000 insertions in non-breastfeeding women.^4-8 The most common symptoms reported by patients with a perforated IUD are pain and/or bleeding.⁸ Investigators in the European Active Surveillance Study on Intrauterine Devices (EURAS) enrolled more than 60,000 patients who had an IUD insertion and followed them for 12 months with more than 39,000 followed for up to 60 months.^7,8 The uterine perforation rate per 1,000 IUD insertions in non-breastfeeding women with 60 months of follow-up was 1.6 for the LNG-IUD and 0.8 for the Cu-IUD.⁸ The rate of uterine perforation was much higher in women who are breastfeeding or recently postpartum. In the EURAS study after 60 months of follow-up, the perforation rate per 1,000 insertions among breastfeeding women was 7.9 for the LNG-IUS and 4.7 for the Cu-IUD.⁸

Remarkably very few IUD perforations were detected at the time of insertion, including only 2% of the LNG-IUD insertions and 17% of the Cu-IUD insertions.⁸ Many perforations were not detected until more than 12 months following insertion, including 32% of the LNG-IUD insertions and 22% of the Cu-IUD insertions.⁸ Obviously, an IUD that has completely perforated the uterus and resides in the peritoneal cavity is not an effective contraceptive. For some patients, the IUD perforation was initially diagnosed after they became pregnant, and imaging studies to locate the IUD and assess the pregnancy were initiated. Complete perforation is usually treated with laparoscopy to remove the IUD and reduce the risk of injury to intra-abdominal organs.

Patients with an IUD partial perforation may present with pelvic pain or abnormal uterine bleeding.⁹ An ultrasound study to explore the cause of the presenting symptom may detect the partial perforation. It is estimated that approximately 20% of cases of IUD perforation are partial perforation.⁹ Over time, a partial perforation may progress to a complete perforation. In some cases of partial perforation, the IUD string may still be visible in the cervix, and the IUD may be removed by pulling on the strings.⁸ Hysteroscopy and/or laparoscopy may be needed to remove a partially perforated IUD. Following a partial or complete IUD perforation, if the patient desires to continue with IUD contraception, it would be wise to insert a new IUD under ultrasound guidance or assess proper placement with a postplacement ultrasound.

Continue to: Expulsion...

IUD expulsion occurs in approximately 3% to 11% of patients.^10-13 The age of the patient influences the rate of expulsion. In a study of 2,748 patients with a Cu-IUD, the rate of expulsion by age for patients <20 years, 20–24 years, 25–29 years, 30–34 years, and ≥35 years was 8.2%, 3.2%, 3.0%, 2.3%, and 1.8%, respectively.¹⁰ In this study, age did not influence the rate of IUD removal for pelvic pain or abnormal bleeding, which was 4% to 5% across all age groups.¹⁰ In a study of 5,403 patients with an IUD, the rate of IUD expulsion by age for patients <20 years, 20–29 years, and 30–45 years was 14.6%, 7.3%, and 7.2%, respectively.¹² In this study, the 3-year cumulative rate of expulsion was 10.2%.¹² There was no statistically significant difference in the 3-year cumulative rate of expulsion for the 52-mg LNG-IUD (10.1%) and Cu-IUD (10.7%).¹²

The majority of patients who have an IUD expulsion recognize the event and seek additional contraception care. A few patients first recognize the IUD expulsion when they become pregnant, and imaging studies detect no IUD in the uterus or the peritoneal cavity. In a study of more than 17,000 patients using an LNG-IUD, 108 pregnancies were reported. Seven pregnancies occurred in patients who did not realize their IUD was expelled.¹⁴ Patients who have had an IUD expulsion and receive a new IUD are at increased risk for re-expulsion. For these patients, reinsertion of an IUD could be performed under ultrasound guidance to ensure and document optimal initial IUD position within the uterus, or ultrasound can be obtained postinsertion to document appropriate IUD position.

Malposition—prevalence and management

Our understanding of the prevalence and management of a malpositioned IUD is evolving. For the purposes of this discussion a malpositioned IUD is defined as being in the uterus, but not properly positioned within the uterine cavity. Perforation into the peritoneal cavity and complete expulsion of an IUD are considered separate entities. However, a malpositioned IUD within the uterus may eventually perforate the uterus or be expelled from the body. For example, an IUD embedded in the uterine wall may eventually work its way through the wall and become perforated, residing in the peritoneal cavity. An IUD with the stem in the cervix below the internal os may eventually be expelled from the uterus and leave the body through the vagina.

High-quality ultrasonography, including 2-dimensional (2-D) ultrasound with videoclips or 3-dimensional (3-D) ultrasound with coronal views, has greatly advanced our understanding of the prevalence and characteristics of a malpositioned IUD.^15-18 Ultrasound features of an IUD correctly placed within the uterus include:

• the IUD is in the uterus
• the shaft is in the midline of the uterine cavity
• the shaft of the IUD is not in the endocervix
• the IUD arms are at a 90-degree angle from the shaft
• the top of the IUD is within 2 cm of the fundus
• the IUD is not rotated outside of the cornual plane, inverted or transverse.

Ultrasound imaging has identified multiple types of malpositioned IUDs, including:

• IUD embedded in the myometrium—a portion of the IUD is embedded in the uterine wall
• low-lying IUD—the IUD is low in the uterine cavity but not in the endocervix
• IUD in the endocervix—the stem is in the endocervical canal
• rotated—the IUD is rotated outside the cornual plane
• malpositioned arms—the arms are not at a 90-degree angle to the stem
• the IUD is inverted, transverse, or laterally displaced.

IUD malposition is highly prevalent and has been identified in 10% to 20% of convenience cohorts in which an ultrasound study was performed.^15-18

Benacerraf, Shipp, and Bromley were among the first experts to use ultrasound to detect the high prevalence of malpositioned IUDs among a convenience sample of 167 patients with an IUD undergoing ultrasound for a variety of indications. Using 3-D ultrasound, including reconstructed coronal views, they identified 28 patients (17%) with a malpositioned IUD based on the detection of the IUD “poking into the substance of the uterus or cervix.” Among the patients with a malpositioned IUD, the principal indication for the ultrasound study was pelvic pain (39%) or abnormal uterine bleeding (36%). Among women with a normally sited IUD, pelvic pain (19%) or abnormal uterine bleeding (15%) were less often the principal indication for the ultrasound.¹⁵ The malpositioned IUD was removed in 21 of the 28 cases and the symptoms of pelvic pain or abnormal bleeding resolved in 20 of the 21 patients.¹⁵

Other investigators have confirmed the observation that IUD malposition is common.^16-18 In a retrospective study of 1,748 pelvic ultrasounds performed for any indication where an IUD was present, after excluding 13 patients who were determined to have expelled their IUD (13) and 13 patients with a perforated IUD, 156 patients (8.9%) were diagnosed as having a malpositioned IUD.¹⁶ IUD malposition was diagnosed when the IUD was in the uterus but positioned in the lower uterine segment, cervix, rotated or embedded in the uterus. An IUD in the lower uterine segment or cervix was detected in 133 patients, representing 85% of cases. Among these cases, 29 IUDs were also embedded and/or rotated, indicating that some IUDs have multiple causes of the malposition. Twenty-one IUDs were near the fundus but embedded and/or rotated. Controls with a normally-sited IUD were selected for comparison to the case group. Among IUD users, the identification of suspected adenomyosis on the ultrasound was associated with an increased risk of IUD malposition (odds ratio [OR], 3.04; 95% confidence interval [CI], 1.08-8.52).¹⁶ In this study, removal of a malpositioned LNG-IUD, without initiating a highly reliable contraceptive was associated with an increased risk of pregnancy. It is important to initiate a highly reliable form of contraception if the plan is to remove a malpositioned IUD.^16,19

In a study of 1,253 pelvic ultrasounds performed for any indication where an IUD was identified in the uterus, 263 IUDs (19%) were determined to be malpositioned.¹⁷ In this study the location of the malpositioned IUDs included¹⁷:

• the lower uterine segment not extending into the cervix (38%)
• in the lower uterine segment extending into the cervix (22%)
• in the cervix (26%)
• rotated axis of the IUD (12%)
• other (2%).

Among the 236 malpositioned IUDs, 24% appeared to be embedded in the uterine wall.¹⁷ Compared with patients with a normally-sited IUD on ultrasound, patients with a malpositioned IUD more frequently reported vaginal bleeding (30% vs 19%; P<.005) and pelvic pain (43% vs 30%; P<.002), similar to the findings in the Benacerraf et al. study.¹⁴

Connolly and Fox¹⁸ designed an innovative study to determine the rate of malpositioned IUDs using 2-D ultrasound to ensure proper IUD placement at the time of insertion with a follow-up 3-D ultrasound 8 weeks after insertion to assess IUD position within the uterus. At the 8-week 3-D ultrasound, among 763 women, 16.6% of the IUDs were malpositioned.¹⁸ In this study, IUD position was determined to be correct if all the following features were identified:

• the IUD shaft was in the midline of the uterine cavity
• the IUD arms were at 90 degrees from the stem
• the top of the IUD was within 3 to 4 mm of the fundus
• the IUD was not rotated, inverted or transverse.

IUD malpositions were categorized as:

• embedded in the uterine wall
• low in the uterine cavity
• in the endocervical canal
• misaligned
• perforated
• expulsed.

At the 8-week follow-up, 636 patients (83.4%) had an IUD that was correctly positioned.¹⁸ In 127 patients (16.6%) IUD malposition was identified, with some patients having more than one type of malposition. The types of malposition identified were:

• embedded in the myometrium (54%)
• misaligned, including rotated, laterally displaced, inverted, transverse or arms not deployed (47%)
• low in the uterine cavity (39%)
• in the endocervical canal (14%)
• perforated (3%)
• expulsion (0%).

Recall that all of these patients had a 2-D ultrasound at the time of insertion that identified the IUD as correctly placed. This suggests that during the 8 weeks following IUD placement there were changes in the location of the IUD or that 2-D ultrasound has lower sensitivity than 3-D ultrasound to detect malposition. Of note, at the 8-week follow-up, bleeding or pain was reported by 36% of the patients with a malpositioned IUD and 20% of patients with a correctly positioned IUD.¹⁷ Sixty-seven of the 127 malpositioned IUDs “required” removal, but the precise reasons for the removals were not delineated. The investigators concluded that 3-D ultrasonography is useful for the detection of IUD malposition and could be considered as part of ongoing IUD care, if symptoms of pain or bleeding occur.¹⁸

Continue to: IUD malposition following postplacental insertion...

IUD malposition following postplacental insertion

IUD malposition is common in patients who have had a postplacental insertion. Ultrasound imaging plays an important role in detecting IUD expulsion and malposition in these cases. Postplacental IUD insertion is defined as the placement of an IUD within 10 minutes following delivery of the placenta. Postplacental IUD insertion can be performed following a vaginal or cesarean birth and with a Cu-IUD or LNG-IUD. The good news is that postplacental IUD insertion reduces the risk of unplanned pregnancy in the years following birth. However, postplacental IUD insertion is associated with a high rate of IUD malposition.

In a study of 162 patients who had postplacental insertion of a Cu-IUD following a vaginal birth, ultrasound and physical examination at 6 months demonstrated complete IUD expulsion in 8%, partial expulsion in 16%, and malposition in 15%.²⁰ The IUD was correctly sited in 56% of patients. Seven patients (4%) had the IUD removed, and 1 patient had a perforated IUD. Among the 25 malpositioned IUDs, 14 were not within 1 cm of the fundus, and 11 were rotated outside of the axis of the cornuas. In this study partial expulsion was defined as an IUD protruding from the external cervical os on physical exam or demonstration of the distal tip of the IUD below the internal os of the cervix on ultrasound. Malposition was defined as an IUD that was >1 cm from the fundus or in an abnormal location or axis, but not partially expelled.

In a study of 69 patients who had postplacental insertion of a Cu-IUD following a cesarean birth, ultrasound and physical examination at 6 months demonstrated complete IUD expulsion in 3%, partial expulsion (stem in the cervix below the internal os) in 4% and malposition in 30%.²⁰ The IUD was correctly positioned in 59% of the patients.²¹ The IUD had been electively removed in 3%. Among the 21 patients with a malpositioned IUD, 10 were rotated within the uterine cavity, 6 were inverted (upside down), 3 were low-lying, and 2 were transverse.²¹ Given the relatively high rate of IUD malposition following postplacental insertion, it may be useful to perform a pelvic ultrasound at a postpartum visit to assess the location of the IUD, if ultrasonography is available.

Management of the malpositioned IUD

There are no consensus guidelines on how to care for a patient with a malpositioned IUD. Clinicians need to use their best judgment and engage the patient in joint decision making when managing a malpositioned IUD. When an IUD is malpositioned and the patient has bothersome symptoms of pelvic pain or abnormal bleeding that have not responded to standard interventions, consideration may be given to a remove and replace strategy. When the stem of the IUD is below the level of the internal os on ultrasound or visible at the external os on physical examination, consideration should be given to removing and replacing the IUD. However, if the IUD is removed without replacement or the initiation of a highly reliable contraceptive, the risk of unplanned pregnancy is considerable.^16,19

IUD totally or partially within the cervix or low-lying. When an IUD is in the cervix, the contraceptive efficacy of the IUD may be diminished, especially with a Cu-IUD.²² In these cases, removing and replacing the IUD is an option. In a survey of 20 expert clinicians, >80% recommended replacing an IUD that was totally or partially in the cervical canal.²³ But most of the experts would not replace an IUD that was incidentally noted on ultrasound to be low-lying, being positioned more than 2 cm below the fundus, with no portion of the IUD in the cervical canal. In the same survey, for patients with a low-lying IUD and pelvic pain or bleeding, the majority of experts reported that they would explore other causes of bleeding and pelvic pain not related to the IUD itself and not replace the IUD, but 30% of the experts reported that they would remove and replace the device.²³

IUD embedded in the myometrium with pelvic pain. Based on my clinical experience, when a patient has persistent pelvic pain following the insertion of an IUD and the pain does not resolve with standard measures including medication, an ultrasound study is warranted to assess the position of the IUD. If the ultrasound demonstrates that an arm of the IUD is embedded in the myometrium, removal of the IUD may be associated with resolution of the pain. Reinsertion of an IUD under ultrasound guidance may result in a correctly-sited IUD with no recurrence of pelvic pain.

IUD rotated within the uterus with no pain or abnormal bleeding. For an IUD that is near the fundus and rotated on its axis within the uterus, if the patient has no symptoms of pain or abnormal bleeding, my recommendation to the patient would be to leave the device in situ.

Without available guidelines, engage in clinician-patient discussion

It is clear that IUD malposition is common, occurring in 10% to 20% of patients with an IUD. High-quality ultrasound imaging is helpful in detecting IUD malposition, including 2-D ultrasound with videoclips and/or 3-D ultrasound with coronal reconstruction. More data are needed to identify the best options for managing various types of malpositioned IUDs in patients with and without bothersome symptoms such as pain and bleeding. Until consensus guidelines are developed, clinicians need to engage the patient in a discussion of how to best manage the malpositioned IUD. Medicated IUDs and progestin subdermal implants are our two most effective reversible contraceptives. They are among the most important advances in health care over the past half-century. ●

The medicated intrauterine devices (IUDs), including the levonorgestrel-releasing IUD (LNG-IUD) (Mirena, Kyleena, Skyla, and Liletta) and the copper IUD (Cu-IUD; Paragard), are remarkably effective contraceptives. For the 52-mg LNG-IUD (Mirena, Liletta) the pregnancy rate over 6 years of use averaged less than 0.2% per year.^1,2 For the Cu-IUD, the pregnancy rate over 10 years of use averaged 0.5% per year for the first 3 years of use and 0.2% per year over the following 7 years of use.³ IUD perforation of the uterus, expulsion, and malposition are recognized complications of IUD use. Our understanding of the prevalence and management of malpositioned IUDs is evolving and the main focus of this editorial.

Complete and partial uterus perforation

A complete uterine perforation occurs when the entire IUD is outside the walls of the uterus. A partial uterine perforation occurs when the IUD is outside the uterine cavity, but a portion of the IUD remains in the myometrium. When uterine perforation is suspected, ultrasound can determine if the IUD is properly sited within the uterus. If ultrasonography does not detect the IUD within the uterus, an x-ray of the pelvis and abdomen should be obtained to determine if the IUD is in the peritoneal cavity. If both an ultrasound and a pelvic-abdominal x-ray do not detect the IUD, the IUD was probably expelled from the patient.

Uterine perforation is uncommon and occurs once in every 500 to 1,000 insertions in non-breastfeeding women.^4-8 The most common symptoms reported by patients with a perforated IUD are pain and/or bleeding.⁸ Investigators in the European Active Surveillance Study on Intrauterine Devices (EURAS) enrolled more than 60,000 patients who had an IUD insertion and followed them for 12 months with more than 39,000 followed for up to 60 months.^7,8 The uterine perforation rate per 1,000 IUD insertions in non-breastfeeding women with 60 months of follow-up was 1.6 for the LNG-IUD and 0.8 for the Cu-IUD.⁸ The rate of uterine perforation was much higher in women who are breastfeeding or recently postpartum. In the EURAS study after 60 months of follow-up, the perforation rate per 1,000 insertions among breastfeeding women was 7.9 for the LNG-IUS and 4.7 for the Cu-IUD.⁸

Remarkably very few IUD perforations were detected at the time of insertion, including only 2% of the LNG-IUD insertions and 17% of the Cu-IUD insertions.⁸ Many perforations were not detected until more than 12 months following insertion, including 32% of the LNG-IUD insertions and 22% of the Cu-IUD insertions.⁸ Obviously, an IUD that has completely perforated the uterus and resides in the peritoneal cavity is not an effective contraceptive. For some patients, the IUD perforation was initially diagnosed after they became pregnant, and imaging studies to locate the IUD and assess the pregnancy were initiated. Complete perforation is usually treated with laparoscopy to remove the IUD and reduce the risk of injury to intra-abdominal organs.

Patients with an IUD partial perforation may present with pelvic pain or abnormal uterine bleeding.⁹ An ultrasound study to explore the cause of the presenting symptom may detect the partial perforation. It is estimated that approximately 20% of cases of IUD perforation are partial perforation.⁹ Over time, a partial perforation may progress to a complete perforation. In some cases of partial perforation, the IUD string may still be visible in the cervix, and the IUD may be removed by pulling on the strings.⁸ Hysteroscopy and/or laparoscopy may be needed to remove a partially perforated IUD. Following a partial or complete IUD perforation, if the patient desires to continue with IUD contraception, it would be wise to insert a new IUD under ultrasound guidance or assess proper placement with a postplacement ultrasound.

Continue to: Expulsion...

IUD expulsion occurs in approximately 3% to 11% of patients.^10-13 The age of the patient influences the rate of expulsion. In a study of 2,748 patients with a Cu-IUD, the rate of expulsion by age for patients <20 years, 20–24 years, 25–29 years, 30–34 years, and ≥35 years was 8.2%, 3.2%, 3.0%, 2.3%, and 1.8%, respectively.¹⁰ In this study, age did not influence the rate of IUD removal for pelvic pain or abnormal bleeding, which was 4% to 5% across all age groups.¹⁰ In a study of 5,403 patients with an IUD, the rate of IUD expulsion by age for patients <20 years, 20–29 years, and 30–45 years was 14.6%, 7.3%, and 7.2%, respectively.¹² In this study, the 3-year cumulative rate of expulsion was 10.2%.¹² There was no statistically significant difference in the 3-year cumulative rate of expulsion for the 52-mg LNG-IUD (10.1%) and Cu-IUD (10.7%).¹²

The majority of patients who have an IUD expulsion recognize the event and seek additional contraception care. A few patients first recognize the IUD expulsion when they become pregnant, and imaging studies detect no IUD in the uterus or the peritoneal cavity. In a study of more than 17,000 patients using an LNG-IUD, 108 pregnancies were reported. Seven pregnancies occurred in patients who did not realize their IUD was expelled.¹⁴ Patients who have had an IUD expulsion and receive a new IUD are at increased risk for re-expulsion. For these patients, reinsertion of an IUD could be performed under ultrasound guidance to ensure and document optimal initial IUD position within the uterus, or ultrasound can be obtained postinsertion to document appropriate IUD position.

Malposition—prevalence and management

Our understanding of the prevalence and management of a malpositioned IUD is evolving. For the purposes of this discussion a malpositioned IUD is defined as being in the uterus, but not properly positioned within the uterine cavity. Perforation into the peritoneal cavity and complete expulsion of an IUD are considered separate entities. However, a malpositioned IUD within the uterus may eventually perforate the uterus or be expelled from the body. For example, an IUD embedded in the uterine wall may eventually work its way through the wall and become perforated, residing in the peritoneal cavity. An IUD with the stem in the cervix below the internal os may eventually be expelled from the uterus and leave the body through the vagina.

High-quality ultrasonography, including 2-dimensional (2-D) ultrasound with videoclips or 3-dimensional (3-D) ultrasound with coronal views, has greatly advanced our understanding of the prevalence and characteristics of a malpositioned IUD.^15-18 Ultrasound features of an IUD correctly placed within the uterus include:

• the IUD is in the uterus
• the shaft is in the midline of the uterine cavity
• the shaft of the IUD is not in the endocervix
• the IUD arms are at a 90-degree angle from the shaft
• the top of the IUD is within 2 cm of the fundus
• the IUD is not rotated outside of the cornual plane, inverted or transverse.

Ultrasound imaging has identified multiple types of malpositioned IUDs, including:

• IUD embedded in the myometrium—a portion of the IUD is embedded in the uterine wall
• low-lying IUD—the IUD is low in the uterine cavity but not in the endocervix
• IUD in the endocervix—the stem is in the endocervical canal
• rotated—the IUD is rotated outside the cornual plane
• malpositioned arms—the arms are not at a 90-degree angle to the stem
• the IUD is inverted, transverse, or laterally displaced.

IUD malposition is highly prevalent and has been identified in 10% to 20% of convenience cohorts in which an ultrasound study was performed.^15-18

Benacerraf, Shipp, and Bromley were among the first experts to use ultrasound to detect the high prevalence of malpositioned IUDs among a convenience sample of 167 patients with an IUD undergoing ultrasound for a variety of indications. Using 3-D ultrasound, including reconstructed coronal views, they identified 28 patients (17%) with a malpositioned IUD based on the detection of the IUD “poking into the substance of the uterus or cervix.” Among the patients with a malpositioned IUD, the principal indication for the ultrasound study was pelvic pain (39%) or abnormal uterine bleeding (36%). Among women with a normally sited IUD, pelvic pain (19%) or abnormal uterine bleeding (15%) were less often the principal indication for the ultrasound.¹⁵ The malpositioned IUD was removed in 21 of the 28 cases and the symptoms of pelvic pain or abnormal bleeding resolved in 20 of the 21 patients.¹⁵

Other investigators have confirmed the observation that IUD malposition is common.^16-18 In a retrospective study of 1,748 pelvic ultrasounds performed for any indication where an IUD was present, after excluding 13 patients who were determined to have expelled their IUD (13) and 13 patients with a perforated IUD, 156 patients (8.9%) were diagnosed as having a malpositioned IUD.¹⁶ IUD malposition was diagnosed when the IUD was in the uterus but positioned in the lower uterine segment, cervix, rotated or embedded in the uterus. An IUD in the lower uterine segment or cervix was detected in 133 patients, representing 85% of cases. Among these cases, 29 IUDs were also embedded and/or rotated, indicating that some IUDs have multiple causes of the malposition. Twenty-one IUDs were near the fundus but embedded and/or rotated. Controls with a normally-sited IUD were selected for comparison to the case group. Among IUD users, the identification of suspected adenomyosis on the ultrasound was associated with an increased risk of IUD malposition (odds ratio [OR], 3.04; 95% confidence interval [CI], 1.08-8.52).¹⁶ In this study, removal of a malpositioned LNG-IUD, without initiating a highly reliable contraceptive was associated with an increased risk of pregnancy. It is important to initiate a highly reliable form of contraception if the plan is to remove a malpositioned IUD.^16,19

In a study of 1,253 pelvic ultrasounds performed for any indication where an IUD was identified in the uterus, 263 IUDs (19%) were determined to be malpositioned.¹⁷ In this study the location of the malpositioned IUDs included¹⁷:

• the lower uterine segment not extending into the cervix (38%)
• in the lower uterine segment extending into the cervix (22%)
• in the cervix (26%)
• rotated axis of the IUD (12%)
• other (2%).

Among the 236 malpositioned IUDs, 24% appeared to be embedded in the uterine wall.¹⁷ Compared with patients with a normally-sited IUD on ultrasound, patients with a malpositioned IUD more frequently reported vaginal bleeding (30% vs 19%; P<.005) and pelvic pain (43% vs 30%; P<.002), similar to the findings in the Benacerraf et al. study.¹⁴

Connolly and Fox¹⁸ designed an innovative study to determine the rate of malpositioned IUDs using 2-D ultrasound to ensure proper IUD placement at the time of insertion with a follow-up 3-D ultrasound 8 weeks after insertion to assess IUD position within the uterus. At the 8-week 3-D ultrasound, among 763 women, 16.6% of the IUDs were malpositioned.¹⁸ In this study, IUD position was determined to be correct if all the following features were identified:

• the IUD shaft was in the midline of the uterine cavity
• the IUD arms were at 90 degrees from the stem
• the top of the IUD was within 3 to 4 mm of the fundus
• the IUD was not rotated, inverted or transverse.

IUD malpositions were categorized as:

• embedded in the uterine wall
• low in the uterine cavity
• in the endocervical canal
• misaligned
• perforated
• expulsed.

At the 8-week follow-up, 636 patients (83.4%) had an IUD that was correctly positioned.¹⁸ In 127 patients (16.6%) IUD malposition was identified, with some patients having more than one type of malposition. The types of malposition identified were:

• embedded in the myometrium (54%)
• misaligned, including rotated, laterally displaced, inverted, transverse or arms not deployed (47%)
• low in the uterine cavity (39%)
• in the endocervical canal (14%)
• perforated (3%)
• expulsion (0%).

Recall that all of these patients had a 2-D ultrasound at the time of insertion that identified the IUD as correctly placed. This suggests that during the 8 weeks following IUD placement there were changes in the location of the IUD or that 2-D ultrasound has lower sensitivity than 3-D ultrasound to detect malposition. Of note, at the 8-week follow-up, bleeding or pain was reported by 36% of the patients with a malpositioned IUD and 20% of patients with a correctly positioned IUD.¹⁷ Sixty-seven of the 127 malpositioned IUDs “required” removal, but the precise reasons for the removals were not delineated. The investigators concluded that 3-D ultrasonography is useful for the detection of IUD malposition and could be considered as part of ongoing IUD care, if symptoms of pain or bleeding occur.¹⁸

Continue to: IUD malposition following postplacental insertion...

IUD malposition following postplacental insertion

IUD malposition is common in patients who have had a postplacental insertion. Ultrasound imaging plays an important role in detecting IUD expulsion and malposition in these cases. Postplacental IUD insertion is defined as the placement of an IUD within 10 minutes following delivery of the placenta. Postplacental IUD insertion can be performed following a vaginal or cesarean birth and with a Cu-IUD or LNG-IUD. The good news is that postplacental IUD insertion reduces the risk of unplanned pregnancy in the years following birth. However, postplacental IUD insertion is associated with a high rate of IUD malposition.

In a study of 162 patients who had postplacental insertion of a Cu-IUD following a vaginal birth, ultrasound and physical examination at 6 months demonstrated complete IUD expulsion in 8%, partial expulsion in 16%, and malposition in 15%.²⁰ The IUD was correctly sited in 56% of patients. Seven patients (4%) had the IUD removed, and 1 patient had a perforated IUD. Among the 25 malpositioned IUDs, 14 were not within 1 cm of the fundus, and 11 were rotated outside of the axis of the cornuas. In this study partial expulsion was defined as an IUD protruding from the external cervical os on physical exam or demonstration of the distal tip of the IUD below the internal os of the cervix on ultrasound. Malposition was defined as an IUD that was >1 cm from the fundus or in an abnormal location or axis, but not partially expelled.

In a study of 69 patients who had postplacental insertion of a Cu-IUD following a cesarean birth, ultrasound and physical examination at 6 months demonstrated complete IUD expulsion in 3%, partial expulsion (stem in the cervix below the internal os) in 4% and malposition in 30%.²⁰ The IUD was correctly positioned in 59% of the patients.²¹ The IUD had been electively removed in 3%. Among the 21 patients with a malpositioned IUD, 10 were rotated within the uterine cavity, 6 were inverted (upside down), 3 were low-lying, and 2 were transverse.²¹ Given the relatively high rate of IUD malposition following postplacental insertion, it may be useful to perform a pelvic ultrasound at a postpartum visit to assess the location of the IUD, if ultrasonography is available.

Management of the malpositioned IUD

There are no consensus guidelines on how to care for a patient with a malpositioned IUD. Clinicians need to use their best judgment and engage the patient in joint decision making when managing a malpositioned IUD. When an IUD is malpositioned and the patient has bothersome symptoms of pelvic pain or abnormal bleeding that have not responded to standard interventions, consideration may be given to a remove and replace strategy. When the stem of the IUD is below the level of the internal os on ultrasound or visible at the external os on physical examination, consideration should be given to removing and replacing the IUD. However, if the IUD is removed without replacement or the initiation of a highly reliable contraceptive, the risk of unplanned pregnancy is considerable.^16,19

IUD totally or partially within the cervix or low-lying. When an IUD is in the cervix, the contraceptive efficacy of the IUD may be diminished, especially with a Cu-IUD.²² In these cases, removing and replacing the IUD is an option. In a survey of 20 expert clinicians, >80% recommended replacing an IUD that was totally or partially in the cervical canal.²³ But most of the experts would not replace an IUD that was incidentally noted on ultrasound to be low-lying, being positioned more than 2 cm below the fundus, with no portion of the IUD in the cervical canal. In the same survey, for patients with a low-lying IUD and pelvic pain or bleeding, the majority of experts reported that they would explore other causes of bleeding and pelvic pain not related to the IUD itself and not replace the IUD, but 30% of the experts reported that they would remove and replace the device.²³

IUD embedded in the myometrium with pelvic pain. Based on my clinical experience, when a patient has persistent pelvic pain following the insertion of an IUD and the pain does not resolve with standard measures including medication, an ultrasound study is warranted to assess the position of the IUD. If the ultrasound demonstrates that an arm of the IUD is embedded in the myometrium, removal of the IUD may be associated with resolution of the pain. Reinsertion of an IUD under ultrasound guidance may result in a correctly-sited IUD with no recurrence of pelvic pain.

IUD rotated within the uterus with no pain or abnormal bleeding. For an IUD that is near the fundus and rotated on its axis within the uterus, if the patient has no symptoms of pain or abnormal bleeding, my recommendation to the patient would be to leave the device in situ.

Without available guidelines, engage in clinician-patient discussion

It is clear that IUD malposition is common, occurring in 10% to 20% of patients with an IUD. High-quality ultrasound imaging is helpful in detecting IUD malposition, including 2-D ultrasound with videoclips and/or 3-D ultrasound with coronal reconstruction. More data are needed to identify the best options for managing various types of malpositioned IUDs in patients with and without bothersome symptoms such as pain and bleeding. Until consensus guidelines are developed, clinicians need to engage the patient in a discussion of how to best manage the malpositioned IUD. Medicated IUDs and progestin subdermal implants are our two most effective reversible contraceptives. They are among the most important advances in health care over the past half-century. ●