Women's Health

Preeclampsia is one of the most significant medical complications in pregnancy because of the acute onset it can have in so many affected patients. This acute onset may then rapidly progress to eclampsia and to severe consequences, including maternal death. In addition, the disorder can occur as early as the late second trimester and can thus impact the timing of delivery and fetal age at birth.

It is an obstetrical syndrome with serious implications for the fetus, the infant at birth, and the mother, and it is one whose incidence has been increasing. A full knowledge of the disease state – its pathophysiology, clinical manifestations, and various therapeutic options, both medical and surgical – is critical for the health and well-being of both the mother and fetus.

A new classification system introduced in 2013 by the American College of Obstetricians and Gynecologists’ Task Force Report on Hypertension in Pregnancy has added further complexity to an already complicated disease. On one hand, attempting to precisely achieve a diagnosis with such an imprecise and insidious disease seems ill advised. On the other hand, it is important to achieve some level of clarity with respect to diagnosis and management. In doing so, we must lean toward overdiagnosis and maintain a low threshold for treatment and intervention in the interest of the mother and infant.

I have engaged Baha M. Sibai, MD, professor of obstetrics, gynecology, and reproductive sciences at the University of Texas McGovern Medical School, Houston, to introduce a practical approach for interpreting and utilizing the ACOG report. This installment is the first of a two-part series in which we hope to provide practical clinical strategies for this complex disease.

Dr. Reece, who specializes in maternal-fetal medicine, is vice president for medical affairs at the University of Maryland, Baltimore, as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. He said he had no relevant financial disclosures. He is the medical editor of this column. Contact him at obnews@MDedge.com.

Preeclampsia is one of the most significant medical complications in pregnancy because of the acute onset it can have in so many affected patients. This acute onset may then rapidly progress to eclampsia and to severe consequences, including maternal death. In addition, the disorder can occur as early as the late second trimester and can thus impact the timing of delivery and fetal age at birth.

It is an obstetrical syndrome with serious implications for the fetus, the infant at birth, and the mother, and it is one whose incidence has been increasing. A full knowledge of the disease state – its pathophysiology, clinical manifestations, and various therapeutic options, both medical and surgical – is critical for the health and well-being of both the mother and fetus.

A new classification system introduced in 2013 by the American College of Obstetricians and Gynecologists’ Task Force Report on Hypertension in Pregnancy has added further complexity to an already complicated disease. On one hand, attempting to precisely achieve a diagnosis with such an imprecise and insidious disease seems ill advised. On the other hand, it is important to achieve some level of clarity with respect to diagnosis and management. In doing so, we must lean toward overdiagnosis and maintain a low threshold for treatment and intervention in the interest of the mother and infant.

I have engaged Baha M. Sibai, MD, professor of obstetrics, gynecology, and reproductive sciences at the University of Texas McGovern Medical School, Houston, to introduce a practical approach for interpreting and utilizing the ACOG report. This installment is the first of a two-part series in which we hope to provide practical clinical strategies for this complex disease.

Dr. Reece, who specializes in maternal-fetal medicine, is vice president for medical affairs at the University of Maryland, Baltimore, as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. He said he had no relevant financial disclosures. He is the medical editor of this column. Contact him at obnews@MDedge.com.

Preeclampsia is one of the most significant medical complications in pregnancy because of the acute onset it can have in so many affected patients. This acute onset may then rapidly progress to eclampsia and to severe consequences, including maternal death. In addition, the disorder can occur as early as the late second trimester and can thus impact the timing of delivery and fetal age at birth.

It is an obstetrical syndrome with serious implications for the fetus, the infant at birth, and the mother, and it is one whose incidence has been increasing. A full knowledge of the disease state – its pathophysiology, clinical manifestations, and various therapeutic options, both medical and surgical – is critical for the health and well-being of both the mother and fetus.

A new classification system introduced in 2013 by the American College of Obstetricians and Gynecologists’ Task Force Report on Hypertension in Pregnancy has added further complexity to an already complicated disease. On one hand, attempting to precisely achieve a diagnosis with such an imprecise and insidious disease seems ill advised. On the other hand, it is important to achieve some level of clarity with respect to diagnosis and management. In doing so, we must lean toward overdiagnosis and maintain a low threshold for treatment and intervention in the interest of the mother and infant.

I have engaged Baha M. Sibai, MD, professor of obstetrics, gynecology, and reproductive sciences at the University of Texas McGovern Medical School, Houston, to introduce a practical approach for interpreting and utilizing the ACOG report. This installment is the first of a two-part series in which we hope to provide practical clinical strategies for this complex disease.

Dr. Reece, who specializes in maternal-fetal medicine, is vice president for medical affairs at the University of Maryland, Baltimore, as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. He said he had no relevant financial disclosures. He is the medical editor of this column. Contact him at obnews@MDedge.com.

Prenatal care always has been in part about identifying women with medical complications including preeclampsia. We have long measured blood pressure, checked the urine for high levels of protein, and monitored weight gain. We still do.

However, over the years, the diagnostic criteria for preeclampsia have evolved, first with the exclusion of edema and more recently with the exclusion of proteinuria as a necessary element of the diagnosis. The American College of Obstetricians and Gynecologists’ Task Force Report, Hypertension in Pregnancy, published in 2013, concluded that while preeclampsia may still be defined by the occurrence of hypertension with proteinuria, it also may be diagnosed when hypertension occurs in association with other multisystemic signs indicative of disease severity. The change came based on evidence that some women develop eclampsia, HELLP syndrome, and other serious complications in the absence of proteinuria.

The 2013 document also attempted to review and clarify various issues relating to the classifications, diagnosis, prediction and prevention, and management of hypertension during pregnancy, including the postpartum period. In many respects, it was successful in doing so. However, there is still much confusion regarding the diagnosis of certain categories of hypertensive disorders – particularly preeclampsia with severe features and superimposed preeclampsia with or without severe features.

While it is difficult to establish precise definitions given the often insidious nature of preeclampsia, it still is important to achieve a higher level of clarity with respect to these categories. Overdiagnosis may be preferable. However, improper classification also may influence management decisions that could prove detrimental to the fetus.
 

Severe gestational hypertension

ACOG’s 2013 Report on Hypertension in Pregnancy classifies hypertensive disorders of pregnancy into these categories: Gestational hypertension (GHTN), preeclampsia, preeclampsia with severe features (this includes HELLP), chronic hypertension (CHTN), superimposed preeclampsia with or without severe features, and eclampsia.

Some of the definitions and diagnostic criteria are clear. For instance, GHTN is defined as the new onset of hypertension after 20 weeks’ gestation in the absence of proteinuria or systemic findings such as thrombocytopenia or impaired liver function. CHTN is defined as hypertension that predates conception or is detected before 20 weeks’ gestation. In both cases there should be elevated blood pressure on two occasions at least 4 hours apart.

A major omission is the lack of a definition for severe GHTN. Removal of this previously well-understood classification category combined with unclear statements regarding preeclampsia with or without severe features has made it difficult for physicians to know in some cases of severe hypertension only what diagnosis a woman should receive and how she should be managed.

I recommend that we maintain the category of severe GHTN, and that it be defined as a systolic blood pressure (BP) greater than or equal to 160 mm Hg and/or diastolic BP greater than or equal to 110 mm Hg on at least two occasions at least 4 hours apart when antihypertensive medications have not been initiated. There should be no proteinuria or severe features such as thrombocytopenia or impaired liver function.

The physician may elect in these cases to administer antihypertensive medication and observe the patient in the hospital. An individualized decision can then be made regarding how the patient should be managed, including whether she should be admitted and whether the pregnancy should continue beyond 34 weeks. Blood pressure, gestational age at diagnosis, the presence or absence of symptoms, and laboratory tests all should be taken into consideration.
 

Preeclampsia with or without severe features

We need to clarify and simplify how we think about GHTN and preeclampsia with or without severe features.

Most cases of preeclampsia will involve new-onset proteinuria, with proteinuria being defined as greater than or equal to 300 mg/day or a protein-creatinine ratio of greater than or equal to 0.3 mg/dL. In cases in which a dipstick test must be used, proteinuria is suggested by a urine protein reading of 1+. (It is important to note that dipstick readings should be taken on two separate occasions.) According to the report, preeclampsia also may be established by the presence of GHTN in association with any one of a list of features that are generally referred to as “severe features.”

Various boxes and textual descriptions in the report offer a sometimes confusing picture, however, of the terms preeclampsia and preeclampsia with severe features and their differences. For clarification, I recommend that we define preeclampsia with severe features as GHTN (mild or severe) in association with any one of the severe features.
 

Severe features of preeclampsia

• Platelet count less than 100,000/microliter.
• Elevated hepatic transaminases greater than two times the upper limit of normal for specific laboratory adult reference ranges.
• Severe persistent right upper quadrant abdominal pain or epigastric pain unresponsive to analgesics and unexplained by other etiology.
• Serum creatinine greater than 1.1 mg/dL.
• Pulmonary edema.
• Persistent cerebral disturbances such as severe persistent new-onset headaches unresponsive to nonnarcotic analgesics, altered mental status or other neurologic deficits.
• Visual disturbances such as blurred vision, scotomata, photophobia, or loss of vision.

I also suggest that we think of “mild” GHTN (systolic BP of 140-159 mm Hg or diastolic BP 90-109 mm Hg) and preeclampsia without severe features as one in the same, and that we manage them similarly. The presence or absence of proteinuria is currently the only difference diagnostically. The only difference with respect to management – aside from a weekly urine protein check in the case of GHTN – is the frequency of nonstress testing (NST) and amniotic fluid index (AFI) measurement (currently once a week for GHTN and twice a week for preeclampsia).

Given that unnecessary time and energy may be spent differentiating the two when management is essentially the same, I suggest that preeclampsia be diagnosed in any patient with GHTN with or without proteinuria. All patients can then be managed with blood pressure checks twice a week; symptoms and kick count daily; NST and AFI twice a week; estimated fetal weight by ultrasound every third week; lab tests (CBC, liver enzymes, and creatinine) once a week, and delivery at 37 weeks.

Superimposed preeclampsia with or without severe features

As the report states, the recognition of preeclampsia superimposed on chronic hypertension is “perhaps the greatest challenge” in the diagnosis and management of hypertensive disorders in pregnancy. Overdiagnosis “may be preferable,” the report says, given the high risk of adverse pregnancy outcomes with superimposed preeclampsia. On the other hand, it says, a “more stratified approach based on severity and predictors of adverse outcome may be useful” in avoiding unnecessary preterm births.

Ultimately, the task force proposed that we utilize the two categories of “superimposed preeclampsia” and “superimposed preeclampsia with severe features,” and in doing so, it noted that there “often is ambiguity in the diagnosis of superimposed preeclampsia and that the clinical spectrum of disease is broad.” Indeed, the diagnosis of superimposed preeclampsia as presented in the report remains vague and open to interpretation. In my institution, it has created significant confusion.

The report states that superimposed preeclampsia is likely when any of the following are present: 1) a sudden increase in blood pressure that was previously well controlled or escalation of antihypertensive medications to control blood pressure, or 2) new onset of proteinuria or a sudden increase in proteinuria in a woman with known proteinuria before or early in pregnancy.

It is not clear, however, what is considered a sudden increase in blood pressure, and it is concerning that any escalation of medication could potentially prompt this diagnosis. Is an increase in systolic blood pressure from 140 mm Hg to 150 mm Hg or an increase in diastolic blood pressure from 90 mm Hg to 100 mm Hg between two prenatal visits considered a “sudden increase”? Does an increase in methyldopa dosage from 250 mg daily to 500 mg daily to keep blood pressure within the range of mild hypertension mean that the patient should be diagnosed with superimposed preeclampsia? Hypertension is likely to increase and require an escalation of antihypertensive medications as patients with chronic hypertension progress through their pregnancies.

Similarly, a “sudden increase in proteinuria” – or “sudden, substantial, and sustained increases in protein excretion,” as written elsewhere in the report with respect to superimposed preeclampsia – also is undefined. What exactly does this mean? That we lack clinically meaningful parameters and clear descriptions of acceptable criteria/scenarios for observation rather than intervention is troubling, particularly because some of these women may have preexisting renal disease with expected increases and fluctuations in protein excretion during advanced gestation.

We must be cautious about making a diagnosis of superimposed preeclampsia based on changes in blood pressure or urinary protein alone, lest we have unnecessary hospitalizations and interventions. I recommend that the diagnosis of superimposed preeclampsia be made based on either the new onset of proteinuria in association with mild hypertension after 20 weeks or on elevation in blood pressure to severe ranges (systolic BP greater than or equal to160 mm Hg and/or diastolic BP greater than or equal to 110 mm Hg) despite the use of maximum doses of one antihypertensive drug.

Regarding superimposed preeclampsia with severe features, I recommend that in the case of blood pressure elevation, it be diagnosed only after maximal doses of two medications have been used. Specifically, I recommend that superimposed preeclampsia with severe features be defined as either CHTN or superimposed preeclampsia in association with either systolic BP greater than or equal to 160 mm Hg and/or diastolic BP greater than or equal to 110 mm Hg on at least two occasions despite use of maximum doses of labetalol (2,400 mg/day) plus long-acting nifedipine (120 mg/day), or with any of the other severe features.

In a second installment of the Master Class, I will elaborate on the treatment of severe GHTN and address the management of preeclampsia with severe features as well as postpartum management of hypertension during pregnancy.
 

Suggested diagnostic definitions

• Preeclampsia with severe features: GHTN in association with severe features.
• Superimposed preeclampsia: CHTN with either the new onset of proteinuria in association with mild hypertension after 20 weeks, or an elevation in blood pressure to severe ranges (systolic BP greater than or equal to 160 mm Hg and/or diastolic BP greater than or equal to 110 mm Hg) despite the use of the maximal dose of one antihypertensive drug.
• Superimposed preeclampsia with severe features: CHTN or superimposed preeclampsia with severe features or with a rise in blood pressure to severe ranges despite the maximal doses of two antihypertensive drugs (e.g. 2,400 mg/day labetalol plus 120 mg/day long-acting nifedipine).

Note: These definitions reflect adaptations and clarifications of ACOG’s 2013 Task Force Report on Hypertension in Pregnancy.

Dr. Sibai is professor of obstetrics, gynecology, and reproductive sciences at the University of Texas McGovern Medical School, Houston.

Prenatal care always has been in part about identifying women with medical complications including preeclampsia. We have long measured blood pressure, checked the urine for high levels of protein, and monitored weight gain. We still do.

However, over the years, the diagnostic criteria for preeclampsia have evolved, first with the exclusion of edema and more recently with the exclusion of proteinuria as a necessary element of the diagnosis. The American College of Obstetricians and Gynecologists’ Task Force Report, Hypertension in Pregnancy, published in 2013, concluded that while preeclampsia may still be defined by the occurrence of hypertension with proteinuria, it also may be diagnosed when hypertension occurs in association with other multisystemic signs indicative of disease severity. The change came based on evidence that some women develop eclampsia, HELLP syndrome, and other serious complications in the absence of proteinuria.

The 2013 document also attempted to review and clarify various issues relating to the classifications, diagnosis, prediction and prevention, and management of hypertension during pregnancy, including the postpartum period. In many respects, it was successful in doing so. However, there is still much confusion regarding the diagnosis of certain categories of hypertensive disorders – particularly preeclampsia with severe features and superimposed preeclampsia with or without severe features.

While it is difficult to establish precise definitions given the often insidious nature of preeclampsia, it still is important to achieve a higher level of clarity with respect to these categories. Overdiagnosis may be preferable. However, improper classification also may influence management decisions that could prove detrimental to the fetus.
 

Severe gestational hypertension

ACOG’s 2013 Report on Hypertension in Pregnancy classifies hypertensive disorders of pregnancy into these categories: Gestational hypertension (GHTN), preeclampsia, preeclampsia with severe features (this includes HELLP), chronic hypertension (CHTN), superimposed preeclampsia with or without severe features, and eclampsia.

Some of the definitions and diagnostic criteria are clear. For instance, GHTN is defined as the new onset of hypertension after 20 weeks’ gestation in the absence of proteinuria or systemic findings such as thrombocytopenia or impaired liver function. CHTN is defined as hypertension that predates conception or is detected before 20 weeks’ gestation. In both cases there should be elevated blood pressure on two occasions at least 4 hours apart.

A major omission is the lack of a definition for severe GHTN. Removal of this previously well-understood classification category combined with unclear statements regarding preeclampsia with or without severe features has made it difficult for physicians to know in some cases of severe hypertension only what diagnosis a woman should receive and how she should be managed.

I recommend that we maintain the category of severe GHTN, and that it be defined as a systolic blood pressure (BP) greater than or equal to 160 mm Hg and/or diastolic BP greater than or equal to 110 mm Hg on at least two occasions at least 4 hours apart when antihypertensive medications have not been initiated. There should be no proteinuria or severe features such as thrombocytopenia or impaired liver function.

The physician may elect in these cases to administer antihypertensive medication and observe the patient in the hospital. An individualized decision can then be made regarding how the patient should be managed, including whether she should be admitted and whether the pregnancy should continue beyond 34 weeks. Blood pressure, gestational age at diagnosis, the presence or absence of symptoms, and laboratory tests all should be taken into consideration.
 

Preeclampsia with or without severe features

We need to clarify and simplify how we think about GHTN and preeclampsia with or without severe features.

Most cases of preeclampsia will involve new-onset proteinuria, with proteinuria being defined as greater than or equal to 300 mg/day or a protein-creatinine ratio of greater than or equal to 0.3 mg/dL. In cases in which a dipstick test must be used, proteinuria is suggested by a urine protein reading of 1+. (It is important to note that dipstick readings should be taken on two separate occasions.) According to the report, preeclampsia also may be established by the presence of GHTN in association with any one of a list of features that are generally referred to as “severe features.”

Various boxes and textual descriptions in the report offer a sometimes confusing picture, however, of the terms preeclampsia and preeclampsia with severe features and their differences. For clarification, I recommend that we define preeclampsia with severe features as GHTN (mild or severe) in association with any one of the severe features.
 

Severe features of preeclampsia

• Platelet count less than 100,000/microliter.
• Elevated hepatic transaminases greater than two times the upper limit of normal for specific laboratory adult reference ranges.
• Severe persistent right upper quadrant abdominal pain or epigastric pain unresponsive to analgesics and unexplained by other etiology.
• Serum creatinine greater than 1.1 mg/dL.
• Pulmonary edema.
• Persistent cerebral disturbances such as severe persistent new-onset headaches unresponsive to nonnarcotic analgesics, altered mental status or other neurologic deficits.
• Visual disturbances such as blurred vision, scotomata, photophobia, or loss of vision.

I also suggest that we think of “mild” GHTN (systolic BP of 140-159 mm Hg or diastolic BP 90-109 mm Hg) and preeclampsia without severe features as one in the same, and that we manage them similarly. The presence or absence of proteinuria is currently the only difference diagnostically. The only difference with respect to management – aside from a weekly urine protein check in the case of GHTN – is the frequency of nonstress testing (NST) and amniotic fluid index (AFI) measurement (currently once a week for GHTN and twice a week for preeclampsia).

Given that unnecessary time and energy may be spent differentiating the two when management is essentially the same, I suggest that preeclampsia be diagnosed in any patient with GHTN with or without proteinuria. All patients can then be managed with blood pressure checks twice a week; symptoms and kick count daily; NST and AFI twice a week; estimated fetal weight by ultrasound every third week; lab tests (CBC, liver enzymes, and creatinine) once a week, and delivery at 37 weeks.

Superimposed preeclampsia with or without severe features

As the report states, the recognition of preeclampsia superimposed on chronic hypertension is “perhaps the greatest challenge” in the diagnosis and management of hypertensive disorders in pregnancy. Overdiagnosis “may be preferable,” the report says, given the high risk of adverse pregnancy outcomes with superimposed preeclampsia. On the other hand, it says, a “more stratified approach based on severity and predictors of adverse outcome may be useful” in avoiding unnecessary preterm births.

Ultimately, the task force proposed that we utilize the two categories of “superimposed preeclampsia” and “superimposed preeclampsia with severe features,” and in doing so, it noted that there “often is ambiguity in the diagnosis of superimposed preeclampsia and that the clinical spectrum of disease is broad.” Indeed, the diagnosis of superimposed preeclampsia as presented in the report remains vague and open to interpretation. In my institution, it has created significant confusion.

The report states that superimposed preeclampsia is likely when any of the following are present: 1) a sudden increase in blood pressure that was previously well controlled or escalation of antihypertensive medications to control blood pressure, or 2) new onset of proteinuria or a sudden increase in proteinuria in a woman with known proteinuria before or early in pregnancy.

It is not clear, however, what is considered a sudden increase in blood pressure, and it is concerning that any escalation of medication could potentially prompt this diagnosis. Is an increase in systolic blood pressure from 140 mm Hg to 150 mm Hg or an increase in diastolic blood pressure from 90 mm Hg to 100 mm Hg between two prenatal visits considered a “sudden increase”? Does an increase in methyldopa dosage from 250 mg daily to 500 mg daily to keep blood pressure within the range of mild hypertension mean that the patient should be diagnosed with superimposed preeclampsia? Hypertension is likely to increase and require an escalation of antihypertensive medications as patients with chronic hypertension progress through their pregnancies.

Similarly, a “sudden increase in proteinuria” – or “sudden, substantial, and sustained increases in protein excretion,” as written elsewhere in the report with respect to superimposed preeclampsia – also is undefined. What exactly does this mean? That we lack clinically meaningful parameters and clear descriptions of acceptable criteria/scenarios for observation rather than intervention is troubling, particularly because some of these women may have preexisting renal disease with expected increases and fluctuations in protein excretion during advanced gestation.

We must be cautious about making a diagnosis of superimposed preeclampsia based on changes in blood pressure or urinary protein alone, lest we have unnecessary hospitalizations and interventions. I recommend that the diagnosis of superimposed preeclampsia be made based on either the new onset of proteinuria in association with mild hypertension after 20 weeks or on elevation in blood pressure to severe ranges (systolic BP greater than or equal to160 mm Hg and/or diastolic BP greater than or equal to 110 mm Hg) despite the use of maximum doses of one antihypertensive drug.

Regarding superimposed preeclampsia with severe features, I recommend that in the case of blood pressure elevation, it be diagnosed only after maximal doses of two medications have been used. Specifically, I recommend that superimposed preeclampsia with severe features be defined as either CHTN or superimposed preeclampsia in association with either systolic BP greater than or equal to 160 mm Hg and/or diastolic BP greater than or equal to 110 mm Hg on at least two occasions despite use of maximum doses of labetalol (2,400 mg/day) plus long-acting nifedipine (120 mg/day), or with any of the other severe features.

In a second installment of the Master Class, I will elaborate on the treatment of severe GHTN and address the management of preeclampsia with severe features as well as postpartum management of hypertension during pregnancy.
 

Suggested diagnostic definitions

• Preeclampsia with severe features: GHTN in association with severe features.
• Superimposed preeclampsia: CHTN with either the new onset of proteinuria in association with mild hypertension after 20 weeks, or an elevation in blood pressure to severe ranges (systolic BP greater than or equal to 160 mm Hg and/or diastolic BP greater than or equal to 110 mm Hg) despite the use of the maximal dose of one antihypertensive drug.
• Superimposed preeclampsia with severe features: CHTN or superimposed preeclampsia with severe features or with a rise in blood pressure to severe ranges despite the maximal doses of two antihypertensive drugs (e.g. 2,400 mg/day labetalol plus 120 mg/day long-acting nifedipine).

Note: These definitions reflect adaptations and clarifications of ACOG’s 2013 Task Force Report on Hypertension in Pregnancy.

Dr. Sibai is professor of obstetrics, gynecology, and reproductive sciences at the University of Texas McGovern Medical School, Houston.

Prenatal care always has been in part about identifying women with medical complications including preeclampsia. We have long measured blood pressure, checked the urine for high levels of protein, and monitored weight gain. We still do.

However, over the years, the diagnostic criteria for preeclampsia have evolved, first with the exclusion of edema and more recently with the exclusion of proteinuria as a necessary element of the diagnosis. The American College of Obstetricians and Gynecologists’ Task Force Report, Hypertension in Pregnancy, published in 2013, concluded that while preeclampsia may still be defined by the occurrence of hypertension with proteinuria, it also may be diagnosed when hypertension occurs in association with other multisystemic signs indicative of disease severity. The change came based on evidence that some women develop eclampsia, HELLP syndrome, and other serious complications in the absence of proteinuria.

The 2013 document also attempted to review and clarify various issues relating to the classifications, diagnosis, prediction and prevention, and management of hypertension during pregnancy, including the postpartum period. In many respects, it was successful in doing so. However, there is still much confusion regarding the diagnosis of certain categories of hypertensive disorders – particularly preeclampsia with severe features and superimposed preeclampsia with or without severe features.

While it is difficult to establish precise definitions given the often insidious nature of preeclampsia, it still is important to achieve a higher level of clarity with respect to these categories. Overdiagnosis may be preferable. However, improper classification also may influence management decisions that could prove detrimental to the fetus.
 

Severe gestational hypertension

ACOG’s 2013 Report on Hypertension in Pregnancy classifies hypertensive disorders of pregnancy into these categories: Gestational hypertension (GHTN), preeclampsia, preeclampsia with severe features (this includes HELLP), chronic hypertension (CHTN), superimposed preeclampsia with or without severe features, and eclampsia.

Some of the definitions and diagnostic criteria are clear. For instance, GHTN is defined as the new onset of hypertension after 20 weeks’ gestation in the absence of proteinuria or systemic findings such as thrombocytopenia or impaired liver function. CHTN is defined as hypertension that predates conception or is detected before 20 weeks’ gestation. In both cases there should be elevated blood pressure on two occasions at least 4 hours apart.

A major omission is the lack of a definition for severe GHTN. Removal of this previously well-understood classification category combined with unclear statements regarding preeclampsia with or without severe features has made it difficult for physicians to know in some cases of severe hypertension only what diagnosis a woman should receive and how she should be managed.

I recommend that we maintain the category of severe GHTN, and that it be defined as a systolic blood pressure (BP) greater than or equal to 160 mm Hg and/or diastolic BP greater than or equal to 110 mm Hg on at least two occasions at least 4 hours apart when antihypertensive medications have not been initiated. There should be no proteinuria or severe features such as thrombocytopenia or impaired liver function.

The physician may elect in these cases to administer antihypertensive medication and observe the patient in the hospital. An individualized decision can then be made regarding how the patient should be managed, including whether she should be admitted and whether the pregnancy should continue beyond 34 weeks. Blood pressure, gestational age at diagnosis, the presence or absence of symptoms, and laboratory tests all should be taken into consideration.
 

Preeclampsia with or without severe features

We need to clarify and simplify how we think about GHTN and preeclampsia with or without severe features.

Most cases of preeclampsia will involve new-onset proteinuria, with proteinuria being defined as greater than or equal to 300 mg/day or a protein-creatinine ratio of greater than or equal to 0.3 mg/dL. In cases in which a dipstick test must be used, proteinuria is suggested by a urine protein reading of 1+. (It is important to note that dipstick readings should be taken on two separate occasions.) According to the report, preeclampsia also may be established by the presence of GHTN in association with any one of a list of features that are generally referred to as “severe features.”

Various boxes and textual descriptions in the report offer a sometimes confusing picture, however, of the terms preeclampsia and preeclampsia with severe features and their differences. For clarification, I recommend that we define preeclampsia with severe features as GHTN (mild or severe) in association with any one of the severe features.
 

Severe features of preeclampsia

• Platelet count less than 100,000/microliter.
• Elevated hepatic transaminases greater than two times the upper limit of normal for specific laboratory adult reference ranges.
• Severe persistent right upper quadrant abdominal pain or epigastric pain unresponsive to analgesics and unexplained by other etiology.
• Serum creatinine greater than 1.1 mg/dL.
• Pulmonary edema.
• Persistent cerebral disturbances such as severe persistent new-onset headaches unresponsive to nonnarcotic analgesics, altered mental status or other neurologic deficits.
• Visual disturbances such as blurred vision, scotomata, photophobia, or loss of vision.

I also suggest that we think of “mild” GHTN (systolic BP of 140-159 mm Hg or diastolic BP 90-109 mm Hg) and preeclampsia without severe features as one in the same, and that we manage them similarly. The presence or absence of proteinuria is currently the only difference diagnostically. The only difference with respect to management – aside from a weekly urine protein check in the case of GHTN – is the frequency of nonstress testing (NST) and amniotic fluid index (AFI) measurement (currently once a week for GHTN and twice a week for preeclampsia).

Given that unnecessary time and energy may be spent differentiating the two when management is essentially the same, I suggest that preeclampsia be diagnosed in any patient with GHTN with or without proteinuria. All patients can then be managed with blood pressure checks twice a week; symptoms and kick count daily; NST and AFI twice a week; estimated fetal weight by ultrasound every third week; lab tests (CBC, liver enzymes, and creatinine) once a week, and delivery at 37 weeks.

Superimposed preeclampsia with or without severe features

As the report states, the recognition of preeclampsia superimposed on chronic hypertension is “perhaps the greatest challenge” in the diagnosis and management of hypertensive disorders in pregnancy. Overdiagnosis “may be preferable,” the report says, given the high risk of adverse pregnancy outcomes with superimposed preeclampsia. On the other hand, it says, a “more stratified approach based on severity and predictors of adverse outcome may be useful” in avoiding unnecessary preterm births.

Ultimately, the task force proposed that we utilize the two categories of “superimposed preeclampsia” and “superimposed preeclampsia with severe features,” and in doing so, it noted that there “often is ambiguity in the diagnosis of superimposed preeclampsia and that the clinical spectrum of disease is broad.” Indeed, the diagnosis of superimposed preeclampsia as presented in the report remains vague and open to interpretation. In my institution, it has created significant confusion.

The report states that superimposed preeclampsia is likely when any of the following are present: 1) a sudden increase in blood pressure that was previously well controlled or escalation of antihypertensive medications to control blood pressure, or 2) new onset of proteinuria or a sudden increase in proteinuria in a woman with known proteinuria before or early in pregnancy.

It is not clear, however, what is considered a sudden increase in blood pressure, and it is concerning that any escalation of medication could potentially prompt this diagnosis. Is an increase in systolic blood pressure from 140 mm Hg to 150 mm Hg or an increase in diastolic blood pressure from 90 mm Hg to 100 mm Hg between two prenatal visits considered a “sudden increase”? Does an increase in methyldopa dosage from 250 mg daily to 500 mg daily to keep blood pressure within the range of mild hypertension mean that the patient should be diagnosed with superimposed preeclampsia? Hypertension is likely to increase and require an escalation of antihypertensive medications as patients with chronic hypertension progress through their pregnancies.

Similarly, a “sudden increase in proteinuria” – or “sudden, substantial, and sustained increases in protein excretion,” as written elsewhere in the report with respect to superimposed preeclampsia – also is undefined. What exactly does this mean? That we lack clinically meaningful parameters and clear descriptions of acceptable criteria/scenarios for observation rather than intervention is troubling, particularly because some of these women may have preexisting renal disease with expected increases and fluctuations in protein excretion during advanced gestation.

We must be cautious about making a diagnosis of superimposed preeclampsia based on changes in blood pressure or urinary protein alone, lest we have unnecessary hospitalizations and interventions. I recommend that the diagnosis of superimposed preeclampsia be made based on either the new onset of proteinuria in association with mild hypertension after 20 weeks or on elevation in blood pressure to severe ranges (systolic BP greater than or equal to160 mm Hg and/or diastolic BP greater than or equal to 110 mm Hg) despite the use of maximum doses of one antihypertensive drug.

Regarding superimposed preeclampsia with severe features, I recommend that in the case of blood pressure elevation, it be diagnosed only after maximal doses of two medications have been used. Specifically, I recommend that superimposed preeclampsia with severe features be defined as either CHTN or superimposed preeclampsia in association with either systolic BP greater than or equal to 160 mm Hg and/or diastolic BP greater than or equal to 110 mm Hg on at least two occasions despite use of maximum doses of labetalol (2,400 mg/day) plus long-acting nifedipine (120 mg/day), or with any of the other severe features.

In a second installment of the Master Class, I will elaborate on the treatment of severe GHTN and address the management of preeclampsia with severe features as well as postpartum management of hypertension during pregnancy.
 

Suggested diagnostic definitions

• Preeclampsia with severe features: GHTN in association with severe features.
• Superimposed preeclampsia: CHTN with either the new onset of proteinuria in association with mild hypertension after 20 weeks, or an elevation in blood pressure to severe ranges (systolic BP greater than or equal to 160 mm Hg and/or diastolic BP greater than or equal to 110 mm Hg) despite the use of the maximal dose of one antihypertensive drug.
• Superimposed preeclampsia with severe features: CHTN or superimposed preeclampsia with severe features or with a rise in blood pressure to severe ranges despite the maximal doses of two antihypertensive drugs (e.g. 2,400 mg/day labetalol plus 120 mg/day long-acting nifedipine).

Note: These definitions reflect adaptations and clarifications of ACOG’s 2013 Task Force Report on Hypertension in Pregnancy.

Dr. Sibai is professor of obstetrics, gynecology, and reproductive sciences at the University of Texas McGovern Medical School, Houston.

A new diagnostic test that can help clinicians ascertain a patient’s menopausal status has been approved for marketing by the Food and Drug Administration.

The PicoAMH Elisa diagnostic test measures circulating levels of anti-Müllerian hormone (AMH), a granulosa cell product in ovaries that is present only until menopause. In research settings, AMH levels have been used to predict menopause and to confirm the occurrence of menopause; levels have been shown to track well with antral follicle count (J Clin Endocrinol Metab. 2011 Aug 1;96[8]:2532-9).

“Diagnostic results about a woman’s menopausal status may prompt discussions about preventative care for women experiencing menopausal symptoms,” Courtney H. Lias, PhD, director of the division of chemistry and toxicology devices in the FDA’s Center for Devices and Radiological Health, said in a press release announcing the marketing permission. “This test, when used in conjunction with other clinical assessments and laboratory findings, can help inform discussions about preventative care, such as ways to help prevent loss in bone mineral density or to address cardiovascular disease, both of which are known to increase after menopause.”

As Dr. Lias emphasized, the new test is designed to be used along with a thorough clinical assessment and other laboratory tests. Having a reliable test for circulating AMH for clinical use allows measurement of a hormone that, unlike follicle stimulating hormone and luteinizing hormone, does not fluctuate throughout the menstrual cycle for premenopausal women.

JoAnn Pinkerton, MD, executive director of the North American Menopause Society, provided clinical context about the utility of the new assay. “AMH levels appear to provide valuable information about timing of menopause. While not needed for women undergoing a natural menopause at age 51, it will be very helpful for women at risk of early ovarian failure, such as following chemotherapy for cancer or genetic or endocrine reasons,” said Dr. Pinkerton. “Women desiring pregnancy who are skipping periods can be more reassured if their AMH is normal, as studies suggest, that AMH is highly predictive of timing of menopause.”*

In permitting marketing of the PicoAMH Elisa assay, the FDA looked at data drawn from the Study of Women’s Health Across the Nation. For 690 women aged 42-62 years, “the PicoAMH Elisa test performed reasonably well at determining levels of AMH in the blood,” the FDA said in the press release. The test also was able to identify women who had already had their last menstrual period, and to determine women who were at least 5 years away from stopping menstruation, according to the longitudinal study.

The PicoAMH Elisa test will be marketed by Ansh Labs. Since the device’s review went through a de novo premarket pathway designed for novel devices of low to medium risk, there will be an additional set of criteria, called special controls, put in place to monitor the safety and effectiveness of the test.

*This article was updated on 10/26/2018.

A new diagnostic test that can help clinicians ascertain a patient’s menopausal status has been approved for marketing by the Food and Drug Administration.

The PicoAMH Elisa diagnostic test measures circulating levels of anti-Müllerian hormone (AMH), a granulosa cell product in ovaries that is present only until menopause. In research settings, AMH levels have been used to predict menopause and to confirm the occurrence of menopause; levels have been shown to track well with antral follicle count (J Clin Endocrinol Metab. 2011 Aug 1;96[8]:2532-9).

“Diagnostic results about a woman’s menopausal status may prompt discussions about preventative care for women experiencing menopausal symptoms,” Courtney H. Lias, PhD, director of the division of chemistry and toxicology devices in the FDA’s Center for Devices and Radiological Health, said in a press release announcing the marketing permission. “This test, when used in conjunction with other clinical assessments and laboratory findings, can help inform discussions about preventative care, such as ways to help prevent loss in bone mineral density or to address cardiovascular disease, both of which are known to increase after menopause.”

As Dr. Lias emphasized, the new test is designed to be used along with a thorough clinical assessment and other laboratory tests. Having a reliable test for circulating AMH for clinical use allows measurement of a hormone that, unlike follicle stimulating hormone and luteinizing hormone, does not fluctuate throughout the menstrual cycle for premenopausal women.

JoAnn Pinkerton, MD, executive director of the North American Menopause Society, provided clinical context about the utility of the new assay. “AMH levels appear to provide valuable information about timing of menopause. While not needed for women undergoing a natural menopause at age 51, it will be very helpful for women at risk of early ovarian failure, such as following chemotherapy for cancer or genetic or endocrine reasons,” said Dr. Pinkerton. “Women desiring pregnancy who are skipping periods can be more reassured if their AMH is normal, as studies suggest, that AMH is highly predictive of timing of menopause.”*

In permitting marketing of the PicoAMH Elisa assay, the FDA looked at data drawn from the Study of Women’s Health Across the Nation. For 690 women aged 42-62 years, “the PicoAMH Elisa test performed reasonably well at determining levels of AMH in the blood,” the FDA said in the press release. The test also was able to identify women who had already had their last menstrual period, and to determine women who were at least 5 years away from stopping menstruation, according to the longitudinal study.

The PicoAMH Elisa test will be marketed by Ansh Labs. Since the device’s review went through a de novo premarket pathway designed for novel devices of low to medium risk, there will be an additional set of criteria, called special controls, put in place to monitor the safety and effectiveness of the test.

*This article was updated on 10/26/2018.

A new diagnostic test that can help clinicians ascertain a patient’s menopausal status has been approved for marketing by the Food and Drug Administration.

The PicoAMH Elisa diagnostic test measures circulating levels of anti-Müllerian hormone (AMH), a granulosa cell product in ovaries that is present only until menopause. In research settings, AMH levels have been used to predict menopause and to confirm the occurrence of menopause; levels have been shown to track well with antral follicle count (J Clin Endocrinol Metab. 2011 Aug 1;96[8]:2532-9).

“Diagnostic results about a woman’s menopausal status may prompt discussions about preventative care for women experiencing menopausal symptoms,” Courtney H. Lias, PhD, director of the division of chemistry and toxicology devices in the FDA’s Center for Devices and Radiological Health, said in a press release announcing the marketing permission. “This test, when used in conjunction with other clinical assessments and laboratory findings, can help inform discussions about preventative care, such as ways to help prevent loss in bone mineral density or to address cardiovascular disease, both of which are known to increase after menopause.”

As Dr. Lias emphasized, the new test is designed to be used along with a thorough clinical assessment and other laboratory tests. Having a reliable test for circulating AMH for clinical use allows measurement of a hormone that, unlike follicle stimulating hormone and luteinizing hormone, does not fluctuate throughout the menstrual cycle for premenopausal women.

JoAnn Pinkerton, MD, executive director of the North American Menopause Society, provided clinical context about the utility of the new assay. “AMH levels appear to provide valuable information about timing of menopause. While not needed for women undergoing a natural menopause at age 51, it will be very helpful for women at risk of early ovarian failure, such as following chemotherapy for cancer or genetic or endocrine reasons,” said Dr. Pinkerton. “Women desiring pregnancy who are skipping periods can be more reassured if their AMH is normal, as studies suggest, that AMH is highly predictive of timing of menopause.”*

In permitting marketing of the PicoAMH Elisa assay, the FDA looked at data drawn from the Study of Women’s Health Across the Nation. For 690 women aged 42-62 years, “the PicoAMH Elisa test performed reasonably well at determining levels of AMH in the blood,” the FDA said in the press release. The test also was able to identify women who had already had their last menstrual period, and to determine women who were at least 5 years away from stopping menstruation, according to the longitudinal study.

The PicoAMH Elisa test will be marketed by Ansh Labs. Since the device’s review went through a de novo premarket pathway designed for novel devices of low to medium risk, there will be an additional set of criteria, called special controls, put in place to monitor the safety and effectiveness of the test.

*This article was updated on 10/26/2018.

I think the question was intended as polite, dinner party chit chat ... maybe an attempt by a gracious hostess to make sure everyone was engaged in conversation.

“So what pediatric infectious disease should parents be most worried about?” she asked me.

I’ll admit that a couple of perfectly respectable and noncontroversial possibilities crossed my mind before I answered.

Acute flaccid myelitis? Measles?

When I replied, “gonorrhea,” conversation at the table pretty much stopped.

Let me explain. Acute flaccid myelitis is a polio-like neurologic condition that has been grabbing headlines. Yes, it is concerning that most cases have occurred in children and some affected children are left with long-term deficits. Technically though, AFM is a neurologic rather than an infectious disease. When cases occur, we suspect a viral infection but according to the Centers for Disease Control and Prevention, no pathogen has been consistently identified from the spinal fluid of infected patients. From August 2014 to September 2018, the CDC received information on 368 confirmed cases, so AFM fortunately is still rare.

News reports describe measles outbreaks raging in Europe – more than 41,000 cases so far this year, and 40 deaths – and warn that the United States could be next. But let’s be honest: We have a safe and effective vaccine for measles and outbreaks like this don’t happen when individuals are appropriately immunized. Parents, immunize your children. If you are lucky enough to be traveling to Europe with your baby, remember that MMR vaccine is indicated for 6- to 11-month olds, but it doesn’t count in the 2-dose series.

But gonorrhea?

In 2017, the World Health Organization included Neisseria gonorrhoeae on its list of bacteria that pose the greatest threat to human health and for which new antibiotics are urgently needed. The popular media are calling N. gonorrhoeae one of the new “superbugs.” Globally, patients are being diagnosed with strains of gonorrhea that are resistant to all commonly used antibiotics. As reported during IDWeek 2018 this October, patients also are being diagnosed in the United States.

CDC

Sancta St. Cyr, MD, of the Centers for Disease Control and Prevention, and her colleagues reported data from the Gonococcal Isolate Surveillance Project (GISP) and trends in multidrug resistant (MDR) and extensively-drug resistant (XDR) gonorrhea in the United States. A gonococcal isolate with resistance or elevated minimum inhibitory concentrations (MIC) to greater than or equal to two classes of antimicrobials is classified as MDR and an isolate with elevated MICs to greater than or equal to three classes of antimicrobials is classified as XDR. The MIC is the lowest antimicrobial concentration that inhibits growth of bacteria in the laboratory and rising MICs – evidence that higher levels of an antibiotic are needed to stop bacterial growth – can be an early indicator that resistance is emerging.

More than 150,000 gonococcal isolates were tested between 1987 and 2016. The first isolates with elevated MICs to cephalosporins and macrolides were identified in 1998, and since 2011, MDR resistance rates have hovered around 1%. In 2016, the rate was 1.1%, down from 1.3% in 2011. A single XDR isolate with resistance to fluoroquinolones with elevated MICs to both cephalosporins and macrolides was identified in 2011.

One could look at these data and ask if this is a “glass half full or half empty” situation, but I propose that clinicians and public health officials should not look at these data and be reassured that rates of MDR-gonorrhea remained stable between 2010 and 2016. According to a recent surveillance report released by the CDC, the absolute number of cases of gonorrhea has continued to rise. In 2017, there were 555,608 cases reported in the United States, a 67% increase since 2013. If we assume that rates of resistance in 2017 were similar to those in 2016, that’s more than 5,000 cases of MDR-gonorrhea in a single year.

“That’s bad,” one of my dining companions agreed. “But is gonorrhea really a pediatric issue?”

To answer that question, we just have to look at the numbers. According to the 2017 Youth Risk Behavior Survey, the percentage of high school students who had ever had sex was approximately 40% and about 10% of students had four or more lifetime partners. More than 45% of sexually active students denied the use of a condom during the last sexual intercourse. Certainly, that puts many teenagers at risk for sexually transmitted infections (STIs). Perhaps it shouldn’t be surprising that public health authorities report that half of all new STIs occur in individuals aged 15-24 years. Moreover, 25% of sexually active adolescent girls contract at least one STI.

Gonorrhea is the second most commonly reported notifiable disease in the United States, and according to the CDC, rates of disease in 2017 were highest among adolescents and young adults. In females specifically, the highest rates of gonorrhea were observed among those aged 20-24 years (684.8 cases per 100,000 females) and 15-19 years (557.4 cases per 100,000 females).

It makes sense that pediatricians and parents advocate for making the reduction of gonorrhea transmission rates a public health priority. We also need to recognize that prompt diagnosis and appropriate treatment are critical. Since 2015, dual therapy with ceftriaxone and azithromycin is the only CDC-recommended treatment for gonorrhea.

At that dinner party, my closest friend, who also happens to be a pediatrician, rolled her eyes and shot me look that I’m sure meant, “Nobody really wants to talk about gonorrhea over dessert.” Still, because she is a good friend she said, “So basically you’re saying that millions of teenagers are getting infected with a form of gonorrhea that takes at least two antibiotics to treat, and if this keeps up, we may see kids with untreatable infection. Now that is scary.”

I kept quiet after that but I wanted to mention that in 2017, less than 85% of patients diagnosed with gonorrhea at selected surveillance sites received the recommended treatment with two antibiotics. Patients with inadequately treated gonorrhea are at risk for a host of sequelae. Women can develop pelvic inflammatory disease, abscesses, chronic pelvic pain, and damage of the fallopian tubes that can lead to infertility. Men can develop epididymitis, which occasionally results in infertility. Rarely, N. gonorrhoeae can spread to the blood and cause life-threatening infection. Of course, patients who aren’t treated appropriately may continue to spread the bacteria. Scary? You bet.

For pediatricians who need a refresher course in the treatment of STIs, there are free resources available. The CDC’s 2015 STD Treatment Guidelines are available in a free app; the app contains a nice refresher on taking a sexual history. There also is a print version, wall chart, and pocket guide. Providers also may want to check out the National STD Curriculum offered by the University of Washington STD Prevention Training Center and the University of Washington. Visit https://www.std.uw.edu/.
 

Dr. Bryant is a pediatrician specializing in infectious diseases at the University of Louisville (Ky.) and Norton Children’s Hospital, also in Louisville. She said she had no relevant financial disclosures. Email her at pdnews@mdedge.com.

I think the question was intended as polite, dinner party chit chat ... maybe an attempt by a gracious hostess to make sure everyone was engaged in conversation.

“So what pediatric infectious disease should parents be most worried about?” she asked me.

I’ll admit that a couple of perfectly respectable and noncontroversial possibilities crossed my mind before I answered.

Acute flaccid myelitis? Measles?

When I replied, “gonorrhea,” conversation at the table pretty much stopped.

Let me explain. Acute flaccid myelitis is a polio-like neurologic condition that has been grabbing headlines. Yes, it is concerning that most cases have occurred in children and some affected children are left with long-term deficits. Technically though, AFM is a neurologic rather than an infectious disease. When cases occur, we suspect a viral infection but according to the Centers for Disease Control and Prevention, no pathogen has been consistently identified from the spinal fluid of infected patients. From August 2014 to September 2018, the CDC received information on 368 confirmed cases, so AFM fortunately is still rare.

News reports describe measles outbreaks raging in Europe – more than 41,000 cases so far this year, and 40 deaths – and warn that the United States could be next. But let’s be honest: We have a safe and effective vaccine for measles and outbreaks like this don’t happen when individuals are appropriately immunized. Parents, immunize your children. If you are lucky enough to be traveling to Europe with your baby, remember that MMR vaccine is indicated for 6- to 11-month olds, but it doesn’t count in the 2-dose series.

But gonorrhea?

In 2017, the World Health Organization included Neisseria gonorrhoeae on its list of bacteria that pose the greatest threat to human health and for which new antibiotics are urgently needed. The popular media are calling N. gonorrhoeae one of the new “superbugs.” Globally, patients are being diagnosed with strains of gonorrhea that are resistant to all commonly used antibiotics. As reported during IDWeek 2018 this October, patients also are being diagnosed in the United States.

CDC

Sancta St. Cyr, MD, of the Centers for Disease Control and Prevention, and her colleagues reported data from the Gonococcal Isolate Surveillance Project (GISP) and trends in multidrug resistant (MDR) and extensively-drug resistant (XDR) gonorrhea in the United States. A gonococcal isolate with resistance or elevated minimum inhibitory concentrations (MIC) to greater than or equal to two classes of antimicrobials is classified as MDR and an isolate with elevated MICs to greater than or equal to three classes of antimicrobials is classified as XDR. The MIC is the lowest antimicrobial concentration that inhibits growth of bacteria in the laboratory and rising MICs – evidence that higher levels of an antibiotic are needed to stop bacterial growth – can be an early indicator that resistance is emerging.

More than 150,000 gonococcal isolates were tested between 1987 and 2016. The first isolates with elevated MICs to cephalosporins and macrolides were identified in 1998, and since 2011, MDR resistance rates have hovered around 1%. In 2016, the rate was 1.1%, down from 1.3% in 2011. A single XDR isolate with resistance to fluoroquinolones with elevated MICs to both cephalosporins and macrolides was identified in 2011.

One could look at these data and ask if this is a “glass half full or half empty” situation, but I propose that clinicians and public health officials should not look at these data and be reassured that rates of MDR-gonorrhea remained stable between 2010 and 2016. According to a recent surveillance report released by the CDC, the absolute number of cases of gonorrhea has continued to rise. In 2017, there were 555,608 cases reported in the United States, a 67% increase since 2013. If we assume that rates of resistance in 2017 were similar to those in 2016, that’s more than 5,000 cases of MDR-gonorrhea in a single year.

“That’s bad,” one of my dining companions agreed. “But is gonorrhea really a pediatric issue?”

To answer that question, we just have to look at the numbers. According to the 2017 Youth Risk Behavior Survey, the percentage of high school students who had ever had sex was approximately 40% and about 10% of students had four or more lifetime partners. More than 45% of sexually active students denied the use of a condom during the last sexual intercourse. Certainly, that puts many teenagers at risk for sexually transmitted infections (STIs). Perhaps it shouldn’t be surprising that public health authorities report that half of all new STIs occur in individuals aged 15-24 years. Moreover, 25% of sexually active adolescent girls contract at least one STI.

Gonorrhea is the second most commonly reported notifiable disease in the United States, and according to the CDC, rates of disease in 2017 were highest among adolescents and young adults. In females specifically, the highest rates of gonorrhea were observed among those aged 20-24 years (684.8 cases per 100,000 females) and 15-19 years (557.4 cases per 100,000 females).

It makes sense that pediatricians and parents advocate for making the reduction of gonorrhea transmission rates a public health priority. We also need to recognize that prompt diagnosis and appropriate treatment are critical. Since 2015, dual therapy with ceftriaxone and azithromycin is the only CDC-recommended treatment for gonorrhea.

At that dinner party, my closest friend, who also happens to be a pediatrician, rolled her eyes and shot me look that I’m sure meant, “Nobody really wants to talk about gonorrhea over dessert.” Still, because she is a good friend she said, “So basically you’re saying that millions of teenagers are getting infected with a form of gonorrhea that takes at least two antibiotics to treat, and if this keeps up, we may see kids with untreatable infection. Now that is scary.”

I kept quiet after that but I wanted to mention that in 2017, less than 85% of patients diagnosed with gonorrhea at selected surveillance sites received the recommended treatment with two antibiotics. Patients with inadequately treated gonorrhea are at risk for a host of sequelae. Women can develop pelvic inflammatory disease, abscesses, chronic pelvic pain, and damage of the fallopian tubes that can lead to infertility. Men can develop epididymitis, which occasionally results in infertility. Rarely, N. gonorrhoeae can spread to the blood and cause life-threatening infection. Of course, patients who aren’t treated appropriately may continue to spread the bacteria. Scary? You bet.

For pediatricians who need a refresher course in the treatment of STIs, there are free resources available. The CDC’s 2015 STD Treatment Guidelines are available in a free app; the app contains a nice refresher on taking a sexual history. There also is a print version, wall chart, and pocket guide. Providers also may want to check out the National STD Curriculum offered by the University of Washington STD Prevention Training Center and the University of Washington. Visit https://www.std.uw.edu/.
 

Dr. Bryant is a pediatrician specializing in infectious diseases at the University of Louisville (Ky.) and Norton Children’s Hospital, also in Louisville. She said she had no relevant financial disclosures. Email her at pdnews@mdedge.com.

I think the question was intended as polite, dinner party chit chat ... maybe an attempt by a gracious hostess to make sure everyone was engaged in conversation.

“So what pediatric infectious disease should parents be most worried about?” she asked me.

I’ll admit that a couple of perfectly respectable and noncontroversial possibilities crossed my mind before I answered.

Acute flaccid myelitis? Measles?

When I replied, “gonorrhea,” conversation at the table pretty much stopped.

Let me explain. Acute flaccid myelitis is a polio-like neurologic condition that has been grabbing headlines. Yes, it is concerning that most cases have occurred in children and some affected children are left with long-term deficits. Technically though, AFM is a neurologic rather than an infectious disease. When cases occur, we suspect a viral infection but according to the Centers for Disease Control and Prevention, no pathogen has been consistently identified from the spinal fluid of infected patients. From August 2014 to September 2018, the CDC received information on 368 confirmed cases, so AFM fortunately is still rare.

News reports describe measles outbreaks raging in Europe – more than 41,000 cases so far this year, and 40 deaths – and warn that the United States could be next. But let’s be honest: We have a safe and effective vaccine for measles and outbreaks like this don’t happen when individuals are appropriately immunized. Parents, immunize your children. If you are lucky enough to be traveling to Europe with your baby, remember that MMR vaccine is indicated for 6- to 11-month olds, but it doesn’t count in the 2-dose series.

But gonorrhea?

In 2017, the World Health Organization included Neisseria gonorrhoeae on its list of bacteria that pose the greatest threat to human health and for which new antibiotics are urgently needed. The popular media are calling N. gonorrhoeae one of the new “superbugs.” Globally, patients are being diagnosed with strains of gonorrhea that are resistant to all commonly used antibiotics. As reported during IDWeek 2018 this October, patients also are being diagnosed in the United States.

CDC

Sancta St. Cyr, MD, of the Centers for Disease Control and Prevention, and her colleagues reported data from the Gonococcal Isolate Surveillance Project (GISP) and trends in multidrug resistant (MDR) and extensively-drug resistant (XDR) gonorrhea in the United States. A gonococcal isolate with resistance or elevated minimum inhibitory concentrations (MIC) to greater than or equal to two classes of antimicrobials is classified as MDR and an isolate with elevated MICs to greater than or equal to three classes of antimicrobials is classified as XDR. The MIC is the lowest antimicrobial concentration that inhibits growth of bacteria in the laboratory and rising MICs – evidence that higher levels of an antibiotic are needed to stop bacterial growth – can be an early indicator that resistance is emerging.

More than 150,000 gonococcal isolates were tested between 1987 and 2016. The first isolates with elevated MICs to cephalosporins and macrolides were identified in 1998, and since 2011, MDR resistance rates have hovered around 1%. In 2016, the rate was 1.1%, down from 1.3% in 2011. A single XDR isolate with resistance to fluoroquinolones with elevated MICs to both cephalosporins and macrolides was identified in 2011.

One could look at these data and ask if this is a “glass half full or half empty” situation, but I propose that clinicians and public health officials should not look at these data and be reassured that rates of MDR-gonorrhea remained stable between 2010 and 2016. According to a recent surveillance report released by the CDC, the absolute number of cases of gonorrhea has continued to rise. In 2017, there were 555,608 cases reported in the United States, a 67% increase since 2013. If we assume that rates of resistance in 2017 were similar to those in 2016, that’s more than 5,000 cases of MDR-gonorrhea in a single year.

“That’s bad,” one of my dining companions agreed. “But is gonorrhea really a pediatric issue?”

To answer that question, we just have to look at the numbers. According to the 2017 Youth Risk Behavior Survey, the percentage of high school students who had ever had sex was approximately 40% and about 10% of students had four or more lifetime partners. More than 45% of sexually active students denied the use of a condom during the last sexual intercourse. Certainly, that puts many teenagers at risk for sexually transmitted infections (STIs). Perhaps it shouldn’t be surprising that public health authorities report that half of all new STIs occur in individuals aged 15-24 years. Moreover, 25% of sexually active adolescent girls contract at least one STI.

Gonorrhea is the second most commonly reported notifiable disease in the United States, and according to the CDC, rates of disease in 2017 were highest among adolescents and young adults. In females specifically, the highest rates of gonorrhea were observed among those aged 20-24 years (684.8 cases per 100,000 females) and 15-19 years (557.4 cases per 100,000 females).

It makes sense that pediatricians and parents advocate for making the reduction of gonorrhea transmission rates a public health priority. We also need to recognize that prompt diagnosis and appropriate treatment are critical. Since 2015, dual therapy with ceftriaxone and azithromycin is the only CDC-recommended treatment for gonorrhea.

At that dinner party, my closest friend, who also happens to be a pediatrician, rolled her eyes and shot me look that I’m sure meant, “Nobody really wants to talk about gonorrhea over dessert.” Still, because she is a good friend she said, “So basically you’re saying that millions of teenagers are getting infected with a form of gonorrhea that takes at least two antibiotics to treat, and if this keeps up, we may see kids with untreatable infection. Now that is scary.”

I kept quiet after that but I wanted to mention that in 2017, less than 85% of patients diagnosed with gonorrhea at selected surveillance sites received the recommended treatment with two antibiotics. Patients with inadequately treated gonorrhea are at risk for a host of sequelae. Women can develop pelvic inflammatory disease, abscesses, chronic pelvic pain, and damage of the fallopian tubes that can lead to infertility. Men can develop epididymitis, which occasionally results in infertility. Rarely, N. gonorrhoeae can spread to the blood and cause life-threatening infection. Of course, patients who aren’t treated appropriately may continue to spread the bacteria. Scary? You bet.

For pediatricians who need a refresher course in the treatment of STIs, there are free resources available. The CDC’s 2015 STD Treatment Guidelines are available in a free app; the app contains a nice refresher on taking a sexual history. There also is a print version, wall chart, and pocket guide. Providers also may want to check out the National STD Curriculum offered by the University of Washington STD Prevention Training Center and the University of Washington. Visit https://www.std.uw.edu/.
 

Dr. Bryant is a pediatrician specializing in infectious diseases at the University of Louisville (Ky.) and Norton Children’s Hospital, also in Louisville. She said she had no relevant financial disclosures. Email her at pdnews@mdedge.com.

Women with high and low body mass index in the first trimester of their first pregnancies are at an increased risk of developing postpartum depression, a population-based study of more than 600,000 new mothers shows.

monkeybusinessimages/Thinkstock

“Our findings show a U-shaped association between BMI extremes and clinically significant depression after childbirth,” Michael E. Silverman, PhD, and his associates reported in the Journal of Affective Disorders. “Specifically, women in the lowest and highest groups were at a significantly increased risk for developing [postpartum depression].”

Dr. Silverman and his associates used the Swedish Medical Birth Register to identify women who delivered first live singleton infants from 1997 to 2008. They then calculated the risk of postpartum depression in relation to each woman’s BMI and history of depression. Postpartum depression was defined as a clinical depression diagnosis within 1 year after delivery, Dr. Silverman and his associates wrote.

The investigators found that women with low BMI (less than 18.5 kg/m²) were at an increased postpartum depression risk (relative risk [RR], 1.52; 95% confidence interval, 1.30-1.78), as were those with high BMI (greater than 35 kg/m²) (RR, 1.23; 95% CI, 1.04-1.45).

In addition, an important difference was found between women with low and high BMI.

“Women in the highest BMI group were only at an increased risk for [postpartum depression] if they had no history of depression, showing for the first time how [postpartum depression] risk factors associated with BMI are modified by maternal depression history,” said Dr. Silverman of the department of psychiatry at the Icahn School of Medicine at Mount Sinai, New York, and his associates.

The investigators cited several limitations. For example, only first births were analyzed, which suggests that the incidence of postpartum depression might have been underestimated. Another limitation is that the registry might not have captured women with mild depression. Nevertheless, they said, the study has important implications.

“This study represents the largest and most rigorous exploration into a woman’s early pregnancy BMI as a risk factor for [postpartum depression]. Because pregnant women represent a medically captured population,” they wrote, the findings support implementing preventive strategies for postpartum depression and health literacy for high-risk women.

Dr. Silverman and his associates reported having no conflicts of interest. The study was supported by a grant from the National Institutes of Health.

SOURCE: Silverman ME et al. J Affect Disord. 2018 Nov;240:193-8.

ghenderson@mdedge.com

Women with high and low body mass index in the first trimester of their first pregnancies are at an increased risk of developing postpartum depression, a population-based study of more than 600,000 new mothers shows.

monkeybusinessimages/Thinkstock

“Our findings show a U-shaped association between BMI extremes and clinically significant depression after childbirth,” Michael E. Silverman, PhD, and his associates reported in the Journal of Affective Disorders. “Specifically, women in the lowest and highest groups were at a significantly increased risk for developing [postpartum depression].”

Dr. Silverman and his associates used the Swedish Medical Birth Register to identify women who delivered first live singleton infants from 1997 to 2008. They then calculated the risk of postpartum depression in relation to each woman’s BMI and history of depression. Postpartum depression was defined as a clinical depression diagnosis within 1 year after delivery, Dr. Silverman and his associates wrote.

The investigators found that women with low BMI (less than 18.5 kg/m²) were at an increased postpartum depression risk (relative risk [RR], 1.52; 95% confidence interval, 1.30-1.78), as were those with high BMI (greater than 35 kg/m²) (RR, 1.23; 95% CI, 1.04-1.45).

In addition, an important difference was found between women with low and high BMI.

“Women in the highest BMI group were only at an increased risk for [postpartum depression] if they had no history of depression, showing for the first time how [postpartum depression] risk factors associated with BMI are modified by maternal depression history,” said Dr. Silverman of the department of psychiatry at the Icahn School of Medicine at Mount Sinai, New York, and his associates.

The investigators cited several limitations. For example, only first births were analyzed, which suggests that the incidence of postpartum depression might have been underestimated. Another limitation is that the registry might not have captured women with mild depression. Nevertheless, they said, the study has important implications.

“This study represents the largest and most rigorous exploration into a woman’s early pregnancy BMI as a risk factor for [postpartum depression]. Because pregnant women represent a medically captured population,” they wrote, the findings support implementing preventive strategies for postpartum depression and health literacy for high-risk women.

Dr. Silverman and his associates reported having no conflicts of interest. The study was supported by a grant from the National Institutes of Health.

SOURCE: Silverman ME et al. J Affect Disord. 2018 Nov;240:193-8.

ghenderson@mdedge.com

Women with high and low body mass index in the first trimester of their first pregnancies are at an increased risk of developing postpartum depression, a population-based study of more than 600,000 new mothers shows.

monkeybusinessimages/Thinkstock

“Our findings show a U-shaped association between BMI extremes and clinically significant depression after childbirth,” Michael E. Silverman, PhD, and his associates reported in the Journal of Affective Disorders. “Specifically, women in the lowest and highest groups were at a significantly increased risk for developing [postpartum depression].”

Dr. Silverman and his associates used the Swedish Medical Birth Register to identify women who delivered first live singleton infants from 1997 to 2008. They then calculated the risk of postpartum depression in relation to each woman’s BMI and history of depression. Postpartum depression was defined as a clinical depression diagnosis within 1 year after delivery, Dr. Silverman and his associates wrote.

The investigators found that women with low BMI (less than 18.5 kg/m²) were at an increased postpartum depression risk (relative risk [RR], 1.52; 95% confidence interval, 1.30-1.78), as were those with high BMI (greater than 35 kg/m²) (RR, 1.23; 95% CI, 1.04-1.45).

In addition, an important difference was found between women with low and high BMI.

“Women in the highest BMI group were only at an increased risk for [postpartum depression] if they had no history of depression, showing for the first time how [postpartum depression] risk factors associated with BMI are modified by maternal depression history,” said Dr. Silverman of the department of psychiatry at the Icahn School of Medicine at Mount Sinai, New York, and his associates.

The investigators cited several limitations. For example, only first births were analyzed, which suggests that the incidence of postpartum depression might have been underestimated. Another limitation is that the registry might not have captured women with mild depression. Nevertheless, they said, the study has important implications.

“This study represents the largest and most rigorous exploration into a woman’s early pregnancy BMI as a risk factor for [postpartum depression]. Because pregnant women represent a medically captured population,” they wrote, the findings support implementing preventive strategies for postpartum depression and health literacy for high-risk women.

Dr. Silverman and his associates reported having no conflicts of interest. The study was supported by a grant from the National Institutes of Health.

SOURCE: Silverman ME et al. J Affect Disord. 2018 Nov;240:193-8.

ghenderson@mdedge.com

HIV testing rates were low among women whose sexual behaviors increased their risk of HIV infection, and they were especially low among women who reported having anal sex, according to a report published in the American Journal of Obstetrics & Gynecology.

grandeduc/Thinkstock

Data from the 2011-2015 National Survey of Family Growth were analyzed to estimate the proportion of sexually active, nonpregnant U.S. women aged 15-44 years who had had an HIV test within the past year. The data was stratified by those who reported anal sex and other risk factors, including having more than two sexual partners, condomless sex with a new partner or multiple partners, gonorrhea in the past year, or any history of syphilis, according to Mary Evans, MD, of the National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention at the Centers for Disease Control and Prevention and her colleagues.

Among the 42.4 million sexually active women assessed, 9.0 million (20%) reported they had had anal sex in the past year. Of these, 19% reported that their providers asked about their types of intercourse, and 20% reported an HIV test within the past year. Overall, HIV testing was higher among women who reported anal sex and whose providers asked about types of sex engaged in than it was among those women whose provider did not ask (38% vs. 16%, respectively; P less than .001). However, HIV testing in the past year was higher for women with other forms of risky behaviors as compared with anal sex, ranging from 35.8% to 47.2%.

“Women who report sexual behaviors such as anal sex would benefit from an HIV test and an assessment for [prevention with preexposure prophylaxis] eligibility. Women’s health care providers are uniquely poised to provide HIV prevention for women who tend to have frequent encounters with the health care system,” the researchers concluded.

The authors reported that they had no conflicts of interest.

mlesney@mdedge.com

SOURCE: Evans ME et al. Am J Obstet Gynecol. 2018 Oct;219(4):383.e1-7.

HIV testing rates were low among women whose sexual behaviors increased their risk of HIV infection, and they were especially low among women who reported having anal sex, according to a report published in the American Journal of Obstetrics & Gynecology.

grandeduc/Thinkstock

Data from the 2011-2015 National Survey of Family Growth were analyzed to estimate the proportion of sexually active, nonpregnant U.S. women aged 15-44 years who had had an HIV test within the past year. The data was stratified by those who reported anal sex and other risk factors, including having more than two sexual partners, condomless sex with a new partner or multiple partners, gonorrhea in the past year, or any history of syphilis, according to Mary Evans, MD, of the National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention at the Centers for Disease Control and Prevention and her colleagues.

Among the 42.4 million sexually active women assessed, 9.0 million (20%) reported they had had anal sex in the past year. Of these, 19% reported that their providers asked about their types of intercourse, and 20% reported an HIV test within the past year. Overall, HIV testing was higher among women who reported anal sex and whose providers asked about types of sex engaged in than it was among those women whose provider did not ask (38% vs. 16%, respectively; P less than .001). However, HIV testing in the past year was higher for women with other forms of risky behaviors as compared with anal sex, ranging from 35.8% to 47.2%.

“Women who report sexual behaviors such as anal sex would benefit from an HIV test and an assessment for [prevention with preexposure prophylaxis] eligibility. Women’s health care providers are uniquely poised to provide HIV prevention for women who tend to have frequent encounters with the health care system,” the researchers concluded.

The authors reported that they had no conflicts of interest.

mlesney@mdedge.com

SOURCE: Evans ME et al. Am J Obstet Gynecol. 2018 Oct;219(4):383.e1-7.

HIV testing rates were low among women whose sexual behaviors increased their risk of HIV infection, and they were especially low among women who reported having anal sex, according to a report published in the American Journal of Obstetrics & Gynecology.

grandeduc/Thinkstock

Data from the 2011-2015 National Survey of Family Growth were analyzed to estimate the proportion of sexually active, nonpregnant U.S. women aged 15-44 years who had had an HIV test within the past year. The data was stratified by those who reported anal sex and other risk factors, including having more than two sexual partners, condomless sex with a new partner or multiple partners, gonorrhea in the past year, or any history of syphilis, according to Mary Evans, MD, of the National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention at the Centers for Disease Control and Prevention and her colleagues.

Among the 42.4 million sexually active women assessed, 9.0 million (20%) reported they had had anal sex in the past year. Of these, 19% reported that their providers asked about their types of intercourse, and 20% reported an HIV test within the past year. Overall, HIV testing was higher among women who reported anal sex and whose providers asked about types of sex engaged in than it was among those women whose provider did not ask (38% vs. 16%, respectively; P less than .001). However, HIV testing in the past year was higher for women with other forms of risky behaviors as compared with anal sex, ranging from 35.8% to 47.2%.

“Women who report sexual behaviors such as anal sex would benefit from an HIV test and an assessment for [prevention with preexposure prophylaxis] eligibility. Women’s health care providers are uniquely poised to provide HIV prevention for women who tend to have frequent encounters with the health care system,” the researchers concluded.

The authors reported that they had no conflicts of interest.

mlesney@mdedge.com

SOURCE: Evans ME et al. Am J Obstet Gynecol. 2018 Oct;219(4):383.e1-7.

The risk of adverse cardiac events in female cancer survivors during pregnancy is low unless there is a history of cardiotoxicity, according to Shiying Liu, MD, of the University of Toronto, and her associates.

©Jupiterimages/Thinkstock.com

In a research letter published in the Journal of the American College of Cardiology, Dr. Liu and her associates reported on a retrospective chart review of 78 women with 94 pregnancies who had previously received cancer therapy who were seen at Mount Sinai Hospital between 2005 and 2015. Of these, 15 pregnancies occurred in 13 women with a prior history of cardiotoxicity. The primary outcome was a composite of cardiac events including cardiac death, heart failure (HF), acute coronary syndrome, and sustained arrhythmia.

HF occurred during five pregnancies in four women; no other adverse cardiac events occurred during the study period. All four of the women who experienced HF had a history of cardiotoxicity. There was no difference in age at cancer diagnosis, age at pregnancy, cancer type, or exposure to anthracyclines between those who did and did not experience HF, but women who developed HF were more likely to have left ventricular systolic dysfunction at the first antenatal visit (75% vs. 8%; P = .004) and to be on cardiac medications (50% vs. 8%; P = .026).

“The risk of developing [HF] during pregnancy is rare in female cancer survivors without a history of cardiotoxicity. These women can be reassured that they are at a very low risk of developing [HF] during pregnancy. Women who have a history of cardiotoxicity have an approximately one in three chance of developing [HF] during pregnancy and should receive close cardiac surveillance during pregnancy at a center with expertise in cardiac disease in pregnancy,” the authors concluded.

Coauthor Paaladinesh Thavendiranathan, MD, reported support from the Canadian Institutes of Health Research New Investigator Award. None of the other authors had any relevant financial disclosures.

lfranki@mdedge.com

SOURCE: Liu S et al. J Am Coll Cardiol. 2018 Oct 15. doi: 10.1016/j.jacc.2018.07.085.

The risk of adverse cardiac events in female cancer survivors during pregnancy is low unless there is a history of cardiotoxicity, according to Shiying Liu, MD, of the University of Toronto, and her associates.

©Jupiterimages/Thinkstock.com

In a research letter published in the Journal of the American College of Cardiology, Dr. Liu and her associates reported on a retrospective chart review of 78 women with 94 pregnancies who had previously received cancer therapy who were seen at Mount Sinai Hospital between 2005 and 2015. Of these, 15 pregnancies occurred in 13 women with a prior history of cardiotoxicity. The primary outcome was a composite of cardiac events including cardiac death, heart failure (HF), acute coronary syndrome, and sustained arrhythmia.

HF occurred during five pregnancies in four women; no other adverse cardiac events occurred during the study period. All four of the women who experienced HF had a history of cardiotoxicity. There was no difference in age at cancer diagnosis, age at pregnancy, cancer type, or exposure to anthracyclines between those who did and did not experience HF, but women who developed HF were more likely to have left ventricular systolic dysfunction at the first antenatal visit (75% vs. 8%; P = .004) and to be on cardiac medications (50% vs. 8%; P = .026).

“The risk of developing [HF] during pregnancy is rare in female cancer survivors without a history of cardiotoxicity. These women can be reassured that they are at a very low risk of developing [HF] during pregnancy. Women who have a history of cardiotoxicity have an approximately one in three chance of developing [HF] during pregnancy and should receive close cardiac surveillance during pregnancy at a center with expertise in cardiac disease in pregnancy,” the authors concluded.

Coauthor Paaladinesh Thavendiranathan, MD, reported support from the Canadian Institutes of Health Research New Investigator Award. None of the other authors had any relevant financial disclosures.

lfranki@mdedge.com

SOURCE: Liu S et al. J Am Coll Cardiol. 2018 Oct 15. doi: 10.1016/j.jacc.2018.07.085.

The risk of adverse cardiac events in female cancer survivors during pregnancy is low unless there is a history of cardiotoxicity, according to Shiying Liu, MD, of the University of Toronto, and her associates.

©Jupiterimages/Thinkstock.com

In a research letter published in the Journal of the American College of Cardiology, Dr. Liu and her associates reported on a retrospective chart review of 78 women with 94 pregnancies who had previously received cancer therapy who were seen at Mount Sinai Hospital between 2005 and 2015. Of these, 15 pregnancies occurred in 13 women with a prior history of cardiotoxicity. The primary outcome was a composite of cardiac events including cardiac death, heart failure (HF), acute coronary syndrome, and sustained arrhythmia.

HF occurred during five pregnancies in four women; no other adverse cardiac events occurred during the study period. All four of the women who experienced HF had a history of cardiotoxicity. There was no difference in age at cancer diagnosis, age at pregnancy, cancer type, or exposure to anthracyclines between those who did and did not experience HF, but women who developed HF were more likely to have left ventricular systolic dysfunction at the first antenatal visit (75% vs. 8%; P = .004) and to be on cardiac medications (50% vs. 8%; P = .026).

“The risk of developing [HF] during pregnancy is rare in female cancer survivors without a history of cardiotoxicity. These women can be reassured that they are at a very low risk of developing [HF] during pregnancy. Women who have a history of cardiotoxicity have an approximately one in three chance of developing [HF] during pregnancy and should receive close cardiac surveillance during pregnancy at a center with expertise in cardiac disease in pregnancy,” the authors concluded.

Coauthor Paaladinesh Thavendiranathan, MD, reported support from the Canadian Institutes of Health Research New Investigator Award. None of the other authors had any relevant financial disclosures.

lfranki@mdedge.com

SOURCE: Liu S et al. J Am Coll Cardiol. 2018 Oct 15. doi: 10.1016/j.jacc.2018.07.085.

Annual ultrasound screening of asymptomatic women at risk of epithelial ovarian cancer can lead to lower staging of cancer at detection and improved survival, compared with no screening, according to a prospective clinical trial that followed more than 46,000 women over 2 decades.

“The findings of this study support the concept that a major predictor of ovarian cancer survival is stage at detection,” said John R. van Nagell Jr., MD, of the University of Kentucky–Markey Cancer Center, Lexington, and his coauthors. “The 10-year survival of women whose ovarian cancer was detected at an early stage (I or II) was 35% higher than that of women diagnosed with stage III cancer.” Study results were published in the November issue of Obstetrics & Gynecology.

The study evaluated 46,101 women enrolled in the University of Kentucky Ovarian Cancer Screening Trial over 30.5 years. Trial participants, all of whom had annual ultrasound screening, were age 50 and older, or 25 and older with a family history of ovarian cancer. Overall, 23% and 44% of the women had a family history of either ovarian or breast cancer, respectively. Women in the study had an average of seven scans each. The unscreened comparator group was women with ovarian cancer referred to the UK Markey Cancer Center.

The study detected 71 cases of invasive epithelial ovarian cancers and 17 epithelial ovarian tumors of low malignant potential. None of the women with these tumors had a recurrence. Among the invasive cancers, the majority were either stage I (42%) or II (21%), and none were stage IV. The median age of these patients was 66 years. Of the low-malignancy tumors, 27% were stage I and 73% stage II, with none stage III or IV. A total of 699 women (1.5%) with persistent ovarian tumors had surgery.

Screened women also had improved survival compared to unscreened women: 86% vs. 45% at 5 years, 68% vs. 31% at 10 years (P less than .001).

However, the study also showed a high overall incidence rate for ovarian cancer, including false-positive and false-negative cases, compared with National Cancer Institute reports in the Kentucky state cancer profile: 271 per 100,000 vs. 10.4/100,000.

The study also looked at the economics of annual screening. “Ovarian screening reduced the 10-year mortality by 37% and produced 416 life years gained,” Dr. van Nagell and his coauthors said. Based on an estimated cost of $56 for each transvaginal ultrasound scan, that translates into a cost of $40,731 for each life year gained.

One concern of screening ultrasound is the high false-positive rate. “Although the sensitivity of transvaginal ultrasonography in detecting an ovarian abnormality is high, it has been unreliable in differentiating benign from malignant ovarian tumors,” they said. While they noted the accuracy of assessing malignancy has improved, the risk of complications in women who have surgery for benign tumors is an ongoing concern. “Additional research is necessary to identify high-risk populations who will benefit most from screening.”

Dr. van Nagell and his coauthors reported having no financial relationships. The study was supported by research grants from the Kentucky Department of Health and Human Services and the Telford Foundation.

SOURCE: Van Nagell JR Jr et al. Obstet Gynecol. 2018 Nov;132[5]:1091-100. doi: 10.1097/AOG.0000000000002921.

Annual ultrasound screening of asymptomatic women at risk of epithelial ovarian cancer can lead to lower staging of cancer at detection and improved survival, compared with no screening, according to a prospective clinical trial that followed more than 46,000 women over 2 decades.

“The findings of this study support the concept that a major predictor of ovarian cancer survival is stage at detection,” said John R. van Nagell Jr., MD, of the University of Kentucky–Markey Cancer Center, Lexington, and his coauthors. “The 10-year survival of women whose ovarian cancer was detected at an early stage (I or II) was 35% higher than that of women diagnosed with stage III cancer.” Study results were published in the November issue of Obstetrics & Gynecology.

The study evaluated 46,101 women enrolled in the University of Kentucky Ovarian Cancer Screening Trial over 30.5 years. Trial participants, all of whom had annual ultrasound screening, were age 50 and older, or 25 and older with a family history of ovarian cancer. Overall, 23% and 44% of the women had a family history of either ovarian or breast cancer, respectively. Women in the study had an average of seven scans each. The unscreened comparator group was women with ovarian cancer referred to the UK Markey Cancer Center.

The study detected 71 cases of invasive epithelial ovarian cancers and 17 epithelial ovarian tumors of low malignant potential. None of the women with these tumors had a recurrence. Among the invasive cancers, the majority were either stage I (42%) or II (21%), and none were stage IV. The median age of these patients was 66 years. Of the low-malignancy tumors, 27% were stage I and 73% stage II, with none stage III or IV. A total of 699 women (1.5%) with persistent ovarian tumors had surgery.

Screened women also had improved survival compared to unscreened women: 86% vs. 45% at 5 years, 68% vs. 31% at 10 years (P less than .001).

However, the study also showed a high overall incidence rate for ovarian cancer, including false-positive and false-negative cases, compared with National Cancer Institute reports in the Kentucky state cancer profile: 271 per 100,000 vs. 10.4/100,000.

The study also looked at the economics of annual screening. “Ovarian screening reduced the 10-year mortality by 37% and produced 416 life years gained,” Dr. van Nagell and his coauthors said. Based on an estimated cost of $56 for each transvaginal ultrasound scan, that translates into a cost of $40,731 for each life year gained.

One concern of screening ultrasound is the high false-positive rate. “Although the sensitivity of transvaginal ultrasonography in detecting an ovarian abnormality is high, it has been unreliable in differentiating benign from malignant ovarian tumors,” they said. While they noted the accuracy of assessing malignancy has improved, the risk of complications in women who have surgery for benign tumors is an ongoing concern. “Additional research is necessary to identify high-risk populations who will benefit most from screening.”

Dr. van Nagell and his coauthors reported having no financial relationships. The study was supported by research grants from the Kentucky Department of Health and Human Services and the Telford Foundation.

SOURCE: Van Nagell JR Jr et al. Obstet Gynecol. 2018 Nov;132[5]:1091-100. doi: 10.1097/AOG.0000000000002921.

Annual ultrasound screening of asymptomatic women at risk of epithelial ovarian cancer can lead to lower staging of cancer at detection and improved survival, compared with no screening, according to a prospective clinical trial that followed more than 46,000 women over 2 decades.

“The findings of this study support the concept that a major predictor of ovarian cancer survival is stage at detection,” said John R. van Nagell Jr., MD, of the University of Kentucky–Markey Cancer Center, Lexington, and his coauthors. “The 10-year survival of women whose ovarian cancer was detected at an early stage (I or II) was 35% higher than that of women diagnosed with stage III cancer.” Study results were published in the November issue of Obstetrics & Gynecology.

The study evaluated 46,101 women enrolled in the University of Kentucky Ovarian Cancer Screening Trial over 30.5 years. Trial participants, all of whom had annual ultrasound screening, were age 50 and older, or 25 and older with a family history of ovarian cancer. Overall, 23% and 44% of the women had a family history of either ovarian or breast cancer, respectively. Women in the study had an average of seven scans each. The unscreened comparator group was women with ovarian cancer referred to the UK Markey Cancer Center.

The study detected 71 cases of invasive epithelial ovarian cancers and 17 epithelial ovarian tumors of low malignant potential. None of the women with these tumors had a recurrence. Among the invasive cancers, the majority were either stage I (42%) or II (21%), and none were stage IV. The median age of these patients was 66 years. Of the low-malignancy tumors, 27% were stage I and 73% stage II, with none stage III or IV. A total of 699 women (1.5%) with persistent ovarian tumors had surgery.

Screened women also had improved survival compared to unscreened women: 86% vs. 45% at 5 years, 68% vs. 31% at 10 years (P less than .001).

However, the study also showed a high overall incidence rate for ovarian cancer, including false-positive and false-negative cases, compared with National Cancer Institute reports in the Kentucky state cancer profile: 271 per 100,000 vs. 10.4/100,000.

The study also looked at the economics of annual screening. “Ovarian screening reduced the 10-year mortality by 37% and produced 416 life years gained,” Dr. van Nagell and his coauthors said. Based on an estimated cost of $56 for each transvaginal ultrasound scan, that translates into a cost of $40,731 for each life year gained.

One concern of screening ultrasound is the high false-positive rate. “Although the sensitivity of transvaginal ultrasonography in detecting an ovarian abnormality is high, it has been unreliable in differentiating benign from malignant ovarian tumors,” they said. While they noted the accuracy of assessing malignancy has improved, the risk of complications in women who have surgery for benign tumors is an ongoing concern. “Additional research is necessary to identify high-risk populations who will benefit most from screening.”

Dr. van Nagell and his coauthors reported having no financial relationships. The study was supported by research grants from the Kentucky Department of Health and Human Services and the Telford Foundation.

SOURCE: Van Nagell JR Jr et al. Obstet Gynecol. 2018 Nov;132[5]:1091-100. doi: 10.1097/AOG.0000000000002921.

Endometriosis can mean living with symptoms, multiple surgeries, and infertility for the estimated 10% of U.S. women who experience it, according to a new survey by Health Union, a family of online health communities.

Advances in support and understanding have been made through research and dissemination of information via the Internet, but complete control of endometriosis remains elusive, as only 13% of the 1,239 women surveyed from June 13 to July 14, 2018, said that their condition was under control with their current treatment plan.

Before control, of course, comes diagnosis, and the average gap between onset of symptoms and diagnosis was 8.6 years. Such a gap “can lead to delayed treatment and a potentially negative impact on quality of life,” Health Union said in a written statement. Those years of delays often involved visits to multiple physicians: 44% of respondents saw 3-5 physicians before receiving a diagnosis and 11% had to see 10 or more physicians.

“When comparing differences between symptom onset-to-diagnosis groups, there are some significant findings that suggest a fair amount of progress has been made, for the better,” Health Union said, noting that women who received a diagnosis in less than 5 years “were significantly less likely to think their symptoms were related to their menstrual cycles than those with a longer symptoms-to-diagnosis gap.” Respondents who had a gap of less than 2 years “were more likely to seek medical care as soon as possible” and to have used hormone therapies than those with longer gaps, the group said.

The most common diagnostic tests were laparoscopy, reported by 85% of respondents, and pelvic/transvaginal ultrasound, reported by 46%. Of the women who did not have a laparoscopy, 43% were undergoing a surgical procedure for another condition when their endometriosis was discovered. Laparoscopy also was by far the most common surgery to treat endometriosis, with a 79% prevalence among respondents, compared with 16% for laparotomy and 12% for oophorectomy, Health Union reported in Endometriosis in America 2018.

Common nonsurgical tactics to improve symptoms included increased water intake (79%), use of a heating pad (75%), and increased fresh fruit (64%) or green vegetables (62%) in the diet. Three-quarters of respondents also tried alternative and complementary therapies such as vitamins, exercise, and acupuncture, the report showed.

“Living with endometriosis is much easier now than it was not even a decade ago, as the Internet and social media have definitely increased knowledge about the disease,” said Endometriosis.net (one of the Health Union online communities) patient advocate Laura Kiesel. “When I first suspected I had the disease, in the mid-90s, hardly anyone had heard about it, and those aware of it didn’t think it was very serious. All these years later, I get a lot more sympathy and support – both online and in person – and people understand how serious, painful, and life altering it could be.”

rfranki@mdedge.com

Endometriosis can mean living with symptoms, multiple surgeries, and infertility for the estimated 10% of U.S. women who experience it, according to a new survey by Health Union, a family of online health communities.

Advances in support and understanding have been made through research and dissemination of information via the Internet, but complete control of endometriosis remains elusive, as only 13% of the 1,239 women surveyed from June 13 to July 14, 2018, said that their condition was under control with their current treatment plan.

Before control, of course, comes diagnosis, and the average gap between onset of symptoms and diagnosis was 8.6 years. Such a gap “can lead to delayed treatment and a potentially negative impact on quality of life,” Health Union said in a written statement. Those years of delays often involved visits to multiple physicians: 44% of respondents saw 3-5 physicians before receiving a diagnosis and 11% had to see 10 or more physicians.

“When comparing differences between symptom onset-to-diagnosis groups, there are some significant findings that suggest a fair amount of progress has been made, for the better,” Health Union said, noting that women who received a diagnosis in less than 5 years “were significantly less likely to think their symptoms were related to their menstrual cycles than those with a longer symptoms-to-diagnosis gap.” Respondents who had a gap of less than 2 years “were more likely to seek medical care as soon as possible” and to have used hormone therapies than those with longer gaps, the group said.

The most common diagnostic tests were laparoscopy, reported by 85% of respondents, and pelvic/transvaginal ultrasound, reported by 46%. Of the women who did not have a laparoscopy, 43% were undergoing a surgical procedure for another condition when their endometriosis was discovered. Laparoscopy also was by far the most common surgery to treat endometriosis, with a 79% prevalence among respondents, compared with 16% for laparotomy and 12% for oophorectomy, Health Union reported in Endometriosis in America 2018.

Common nonsurgical tactics to improve symptoms included increased water intake (79%), use of a heating pad (75%), and increased fresh fruit (64%) or green vegetables (62%) in the diet. Three-quarters of respondents also tried alternative and complementary therapies such as vitamins, exercise, and acupuncture, the report showed.

“Living with endometriosis is much easier now than it was not even a decade ago, as the Internet and social media have definitely increased knowledge about the disease,” said Endometriosis.net (one of the Health Union online communities) patient advocate Laura Kiesel. “When I first suspected I had the disease, in the mid-90s, hardly anyone had heard about it, and those aware of it didn’t think it was very serious. All these years later, I get a lot more sympathy and support – both online and in person – and people understand how serious, painful, and life altering it could be.”

rfranki@mdedge.com

Endometriosis can mean living with symptoms, multiple surgeries, and infertility for the estimated 10% of U.S. women who experience it, according to a new survey by Health Union, a family of online health communities.

Advances in support and understanding have been made through research and dissemination of information via the Internet, but complete control of endometriosis remains elusive, as only 13% of the 1,239 women surveyed from June 13 to July 14, 2018, said that their condition was under control with their current treatment plan.

Before control, of course, comes diagnosis, and the average gap between onset of symptoms and diagnosis was 8.6 years. Such a gap “can lead to delayed treatment and a potentially negative impact on quality of life,” Health Union said in a written statement. Those years of delays often involved visits to multiple physicians: 44% of respondents saw 3-5 physicians before receiving a diagnosis and 11% had to see 10 or more physicians.

“When comparing differences between symptom onset-to-diagnosis groups, there are some significant findings that suggest a fair amount of progress has been made, for the better,” Health Union said, noting that women who received a diagnosis in less than 5 years “were significantly less likely to think their symptoms were related to their menstrual cycles than those with a longer symptoms-to-diagnosis gap.” Respondents who had a gap of less than 2 years “were more likely to seek medical care as soon as possible” and to have used hormone therapies than those with longer gaps, the group said.

The most common diagnostic tests were laparoscopy, reported by 85% of respondents, and pelvic/transvaginal ultrasound, reported by 46%. Of the women who did not have a laparoscopy, 43% were undergoing a surgical procedure for another condition when their endometriosis was discovered. Laparoscopy also was by far the most common surgery to treat endometriosis, with a 79% prevalence among respondents, compared with 16% for laparotomy and 12% for oophorectomy, Health Union reported in Endometriosis in America 2018.

Common nonsurgical tactics to improve symptoms included increased water intake (79%), use of a heating pad (75%), and increased fresh fruit (64%) or green vegetables (62%) in the diet. Three-quarters of respondents also tried alternative and complementary therapies such as vitamins, exercise, and acupuncture, the report showed.

“Living with endometriosis is much easier now than it was not even a decade ago, as the Internet and social media have definitely increased knowledge about the disease,” said Endometriosis.net (one of the Health Union online communities) patient advocate Laura Kiesel. “When I first suspected I had the disease, in the mid-90s, hardly anyone had heard about it, and those aware of it didn’t think it was very serious. All these years later, I get a lot more sympathy and support – both online and in person – and people understand how serious, painful, and life altering it could be.”

rfranki@mdedge.com

Regular long-term aspirin use may lower the risk of hepatocellular carcinoma (HCC) and ovarian cancer, adding to the growing evidence that aspirin may play a role as a chemopreventive agent, according to two new studies published in JAMA Oncology.

In the first study, led by Tracey G. Simon, MD, of Massachusetts General Hospital, Boston, the authors evaluated the associations between aspirin dose and duration of use and the risk of developing HCC. They conducted a population-based study, with a pooled analysis of two large prospective U.S. cohort studies: the Nurses’ Health Study and the Health Professionals Follow-up Study. The cohort included a total of 133,371 health care professionals who reported long-term data on aspirin use, frequency, dosage, and duration of use.

For the 87,507 female participants, reporting began in 1980, and for the 45,864 men, reporting began in 1986. The mean age for women was 62 years and was 64 years for men at the midpoint of follow-up (1996). Compared with nonaspirin users, those who used aspirin regularly tended to be older, former smokers, and regularly used statins and multivitamins. During the follow-up period, which was more than 26 years, there were 108 incident cases of HCC (65 women, 43 men; 47 with noncirrhotic HCC).

The investigators found that regular aspirin use was associated with a significantly lower HCC risk versus nonregular use (multivariable hazard ratio, 0.51; 95% confidence interval, 0.34-0.77), and estimates were similar for both sexes. Adjustments for regular NSAID use (for example, at least two tablets per week) did not change the data, and results were similar after further adjustment for coffee consumption and adherence to a healthy diet. The benefit also appeared to be dose related, as compared with nonuse, the multivariable-adjusted HR for HCC was 0.87 (95% CI, 0.51-1.48) for up to 1.5 tablets of standard-dose aspirin per week and 0.51 (95% CI, 0.30-0.86) for 1.5-5 tablets per week. The most benefit was for at least five tablets per week (HR, 0.49; 95% CI, 0.28-0.96; P = .006).

“Our findings add to the growing literature suggesting that the chemopreventive effects of aspirin may extend beyond colorectal cancer,” they wrote.

In the second study, Mollie E. Barnard, ScD, of the Harvard School of Public Health, Boston, and her colleagues looked at whether regular aspirin or NSAID use, as well as the patterns of use, were associated with a lower risk of ovarian cancer.

The data used were obtained from 93,664 women in the Nurses’ Health Study (NHS), who were followed up from 1980 to 2014, and 111,834 people in the Nurses’ Health Study II (NHSII), who were followed up from 1989 to 2015. For each type of agent, including aspirin, low-dose aspirin, nonaspirin NSAIDs, and acetaminophen, they evaluated the timing, duration, frequency, and number of tablets that were used. The mean age of participants in the NHS at baseline was 45.9 years and 34.2 years in the NHSII.

There were 1,054 incident cases of epithelial ovarian cancer identified during the study period. The authors did not detect any significant associations between aspirin and ovarian cancer risk when current users and nonusers were compared, regardless of dose (HR, 0.99; 95% CI, 0.83-1.19). But when low-dose (less than or equal to 100 mg) and standard-dose (325 mg) aspirin were analyzed separately, an inverse association for low-dose aspirin (HR, 0.77; 95% CI, 0.61-0.96) was observed. However, there was no association for standard-dose aspirin (HR, 1.17; 95% CI, 0.92-1.49).

In contrast, use of nonaspirin NSAIDs was positively associated with a higher risk of ovarian cancer when compared with nonuse (HR, 1.19; 95% CI, 1.00-1.41), and there were significant positive trends for duration of use (P = .02) and cumulative average tablets per week (P = .03). No clear associations were identified for acetaminophen use.

“Our results also suggest an increased risk of ovarian cancer among long-term, high-quantity users of nonaspirin analgesics, although this finding may reflect unmeasured confounding,” wrote Dr. Barnard and her coauthors. “Further exploration is warranted to evaluate the mechanisms by which heavy use of aspirin, nonaspirin NSAIDs, and acetaminophen may contribute to the development of ovarian cancer and to replicate our findings.”

The ovarian cancer study was supported by awards from the National Institutes of Health. Dr. Barnard was supported by awards from the National Cancer Institute, and her coauthors had no disclosures to report. The HCC study was funded by an infrastructure grant from the Nurses’ Health Study, an infrastructure grant from the Health Professionals Follow-up Study, and NIH grants to several of the authors. Dr. Chan has previously served as a consultant for Bayer on work unrelated to this article. No other disclosures were reported.

SOURCES: Barnard ME et al. JAMA Oncol. 2018 Oct 4. doi: 10.1001/jamaoncol.2018.4149; Simon TG et al. JAMA Oncol. 2018 Oct 4. doi: 10.1001/jamaoncol.2018.4154.

Regular long-term aspirin use may lower the risk of hepatocellular carcinoma (HCC) and ovarian cancer, adding to the growing evidence that aspirin may play a role as a chemopreventive agent, according to two new studies published in JAMA Oncology.

In the first study, led by Tracey G. Simon, MD, of Massachusetts General Hospital, Boston, the authors evaluated the associations between aspirin dose and duration of use and the risk of developing HCC. They conducted a population-based study, with a pooled analysis of two large prospective U.S. cohort studies: the Nurses’ Health Study and the Health Professionals Follow-up Study. The cohort included a total of 133,371 health care professionals who reported long-term data on aspirin use, frequency, dosage, and duration of use.

For the 87,507 female participants, reporting began in 1980, and for the 45,864 men, reporting began in 1986. The mean age for women was 62 years and was 64 years for men at the midpoint of follow-up (1996). Compared with nonaspirin users, those who used aspirin regularly tended to be older, former smokers, and regularly used statins and multivitamins. During the follow-up period, which was more than 26 years, there were 108 incident cases of HCC (65 women, 43 men; 47 with noncirrhotic HCC).

The investigators found that regular aspirin use was associated with a significantly lower HCC risk versus nonregular use (multivariable hazard ratio, 0.51; 95% confidence interval, 0.34-0.77), and estimates were similar for both sexes. Adjustments for regular NSAID use (for example, at least two tablets per week) did not change the data, and results were similar after further adjustment for coffee consumption and adherence to a healthy diet. The benefit also appeared to be dose related, as compared with nonuse, the multivariable-adjusted HR for HCC was 0.87 (95% CI, 0.51-1.48) for up to 1.5 tablets of standard-dose aspirin per week and 0.51 (95% CI, 0.30-0.86) for 1.5-5 tablets per week. The most benefit was for at least five tablets per week (HR, 0.49; 95% CI, 0.28-0.96; P = .006).

“Our findings add to the growing literature suggesting that the chemopreventive effects of aspirin may extend beyond colorectal cancer,” they wrote.

In the second study, Mollie E. Barnard, ScD, of the Harvard School of Public Health, Boston, and her colleagues looked at whether regular aspirin or NSAID use, as well as the patterns of use, were associated with a lower risk of ovarian cancer.

The data used were obtained from 93,664 women in the Nurses’ Health Study (NHS), who were followed up from 1980 to 2014, and 111,834 people in the Nurses’ Health Study II (NHSII), who were followed up from 1989 to 2015. For each type of agent, including aspirin, low-dose aspirin, nonaspirin NSAIDs, and acetaminophen, they evaluated the timing, duration, frequency, and number of tablets that were used. The mean age of participants in the NHS at baseline was 45.9 years and 34.2 years in the NHSII.

There were 1,054 incident cases of epithelial ovarian cancer identified during the study period. The authors did not detect any significant associations between aspirin and ovarian cancer risk when current users and nonusers were compared, regardless of dose (HR, 0.99; 95% CI, 0.83-1.19). But when low-dose (less than or equal to 100 mg) and standard-dose (325 mg) aspirin were analyzed separately, an inverse association for low-dose aspirin (HR, 0.77; 95% CI, 0.61-0.96) was observed. However, there was no association for standard-dose aspirin (HR, 1.17; 95% CI, 0.92-1.49).

In contrast, use of nonaspirin NSAIDs was positively associated with a higher risk of ovarian cancer when compared with nonuse (HR, 1.19; 95% CI, 1.00-1.41), and there were significant positive trends for duration of use (P = .02) and cumulative average tablets per week (P = .03). No clear associations were identified for acetaminophen use.

“Our results also suggest an increased risk of ovarian cancer among long-term, high-quantity users of nonaspirin analgesics, although this finding may reflect unmeasured confounding,” wrote Dr. Barnard and her coauthors. “Further exploration is warranted to evaluate the mechanisms by which heavy use of aspirin, nonaspirin NSAIDs, and acetaminophen may contribute to the development of ovarian cancer and to replicate our findings.”

The ovarian cancer study was supported by awards from the National Institutes of Health. Dr. Barnard was supported by awards from the National Cancer Institute, and her coauthors had no disclosures to report. The HCC study was funded by an infrastructure grant from the Nurses’ Health Study, an infrastructure grant from the Health Professionals Follow-up Study, and NIH grants to several of the authors. Dr. Chan has previously served as a consultant for Bayer on work unrelated to this article. No other disclosures were reported.

SOURCES: Barnard ME et al. JAMA Oncol. 2018 Oct 4. doi: 10.1001/jamaoncol.2018.4149; Simon TG et al. JAMA Oncol. 2018 Oct 4. doi: 10.1001/jamaoncol.2018.4154.

Regular long-term aspirin use may lower the risk of hepatocellular carcinoma (HCC) and ovarian cancer, adding to the growing evidence that aspirin may play a role as a chemopreventive agent, according to two new studies published in JAMA Oncology.

In the first study, led by Tracey G. Simon, MD, of Massachusetts General Hospital, Boston, the authors evaluated the associations between aspirin dose and duration of use and the risk of developing HCC. They conducted a population-based study, with a pooled analysis of two large prospective U.S. cohort studies: the Nurses’ Health Study and the Health Professionals Follow-up Study. The cohort included a total of 133,371 health care professionals who reported long-term data on aspirin use, frequency, dosage, and duration of use.

For the 87,507 female participants, reporting began in 1980, and for the 45,864 men, reporting began in 1986. The mean age for women was 62 years and was 64 years for men at the midpoint of follow-up (1996). Compared with nonaspirin users, those who used aspirin regularly tended to be older, former smokers, and regularly used statins and multivitamins. During the follow-up period, which was more than 26 years, there were 108 incident cases of HCC (65 women, 43 men; 47 with noncirrhotic HCC).

The investigators found that regular aspirin use was associated with a significantly lower HCC risk versus nonregular use (multivariable hazard ratio, 0.51; 95% confidence interval, 0.34-0.77), and estimates were similar for both sexes. Adjustments for regular NSAID use (for example, at least two tablets per week) did not change the data, and results were similar after further adjustment for coffee consumption and adherence to a healthy diet. The benefit also appeared to be dose related, as compared with nonuse, the multivariable-adjusted HR for HCC was 0.87 (95% CI, 0.51-1.48) for up to 1.5 tablets of standard-dose aspirin per week and 0.51 (95% CI, 0.30-0.86) for 1.5-5 tablets per week. The most benefit was for at least five tablets per week (HR, 0.49; 95% CI, 0.28-0.96; P = .006).

“Our findings add to the growing literature suggesting that the chemopreventive effects of aspirin may extend beyond colorectal cancer,” they wrote.

In the second study, Mollie E. Barnard, ScD, of the Harvard School of Public Health, Boston, and her colleagues looked at whether regular aspirin or NSAID use, as well as the patterns of use, were associated with a lower risk of ovarian cancer.

The data used were obtained from 93,664 women in the Nurses’ Health Study (NHS), who were followed up from 1980 to 2014, and 111,834 people in the Nurses’ Health Study II (NHSII), who were followed up from 1989 to 2015. For each type of agent, including aspirin, low-dose aspirin, nonaspirin NSAIDs, and acetaminophen, they evaluated the timing, duration, frequency, and number of tablets that were used. The mean age of participants in the NHS at baseline was 45.9 years and 34.2 years in the NHSII.

There were 1,054 incident cases of epithelial ovarian cancer identified during the study period. The authors did not detect any significant associations between aspirin and ovarian cancer risk when current users and nonusers were compared, regardless of dose (HR, 0.99; 95% CI, 0.83-1.19). But when low-dose (less than or equal to 100 mg) and standard-dose (325 mg) aspirin were analyzed separately, an inverse association for low-dose aspirin (HR, 0.77; 95% CI, 0.61-0.96) was observed. However, there was no association for standard-dose aspirin (HR, 1.17; 95% CI, 0.92-1.49).

In contrast, use of nonaspirin NSAIDs was positively associated with a higher risk of ovarian cancer when compared with nonuse (HR, 1.19; 95% CI, 1.00-1.41), and there were significant positive trends for duration of use (P = .02) and cumulative average tablets per week (P = .03). No clear associations were identified for acetaminophen use.

“Our results also suggest an increased risk of ovarian cancer among long-term, high-quantity users of nonaspirin analgesics, although this finding may reflect unmeasured confounding,” wrote Dr. Barnard and her coauthors. “Further exploration is warranted to evaluate the mechanisms by which heavy use of aspirin, nonaspirin NSAIDs, and acetaminophen may contribute to the development of ovarian cancer and to replicate our findings.”

The ovarian cancer study was supported by awards from the National Institutes of Health. Dr. Barnard was supported by awards from the National Cancer Institute, and her coauthors had no disclosures to report. The HCC study was funded by an infrastructure grant from the Nurses’ Health Study, an infrastructure grant from the Health Professionals Follow-up Study, and NIH grants to several of the authors. Dr. Chan has previously served as a consultant for Bayer on work unrelated to this article. No other disclosures were reported.

SOURCES: Barnard ME et al. JAMA Oncol. 2018 Oct 4. doi: 10.1001/jamaoncol.2018.4149; Simon TG et al. JAMA Oncol. 2018 Oct 4. doi: 10.1001/jamaoncol.2018.4154.