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Mixed rotavirus vaccine schedules safe and effective
Mixing the RotaTeq and Rotarix rotavirus vaccines schedules resulted in noninferior immunogenicity compared with using only one vaccine schedule, found a new multicenter, open-label study. Safety profiles were also similar among mixed-vaccine and single-vaccine groups, according to Dr. Romina Libster of Vanderbilt University, Nashville, Tenn., and her associates.
“These encouraging data are supported by an earlier study involving precursors of both vaccines and natural rotavirus infections,” wrote Dr. Libster and her colleagues online (Pediatrics. 2016 Jan 28. doi: 10.1542/peds.2015-2603).
The researchers randomly assigned 1,393 healthy infants who were between 6 and 14 weeks old to receive one of five different rotavirus vaccine schedules. The children, enrolled from March 2011 through September 2013, either received all doses from one vaccine or a mixture of the two different rotavirus vaccines, concurrently with other routine immunizations, accordingly:
• 244 children received three doses of RotaTeq (RV5), a live, oral vaccine containing a combination of five human-bovine reassortant rotaviruses.
• 330 children received two doses of Rotarix (RV1), a live-attenuated human rotavirus vaccine from a single human strain.
• 250 children received one dose of RotaTeq, followed by two doses of Rotarix.
• 240 children received two consecutive doses of RotaTeq followed by a dose of Rotarix.
• 329 children received one dose of Rotarix, followed by two consecutive doses of RotaTeq.
Among the 1,236 infants remaining in the study at follow-up, 77%-96% of them across the study groups attained seropositivity defined as IgA greater than or equal to 20 U/mL against at least one vaccine antigen 1 month after the last vaccine dose. Each of the mixed schedules was noninferior to each of the single-vaccine–type schedules.
In fact, a significantly greater proportion of infants receiving one Rotarix vaccine dose followed by two RotaTeq doses achieved seropositivity against both WC3 and 89-12, compared with those receiving two Rotarix doses. Similarly, infants receiving two doses of RotaTeq and one dose of Rotarix (in either order) had higher average titers against WC3 and 89-12 than infants in either of the single-vaccine groups.
“As this study was not aimed to evaluate vaccine efficacy and there is a gap of knowledge regarding a precise correlate of protection for rotavirus vaccine, the clinical relevance of the differences in immunogenicity is unclear,” the authors wrote.
No significant differences in rates of fever, diarrhea, or vomiting occurred when comparing the RV5-RV1-RV1 and RV5-RV5-RV1 groups to the single RotaTeq (RV4) group. The RV1-RV5-RV5 group, however, showed significantly more fever and vomiting than did the single Rotarix group.
“However, when the associations between group and presence of solicited symptoms were stratified by vaccine dose, there were no statistically significant differences between the two groups for the first or second doses of rotavirus vaccine,” the authors wrote.
The most commonly reported adverse event was irritability. Of 70 infants hospitalized during the study, only one case was linked to the vaccine: a 2-month-old girl receiving two doses of Rotarix and diagnosed after the first dose with gastroenteritis concurrent with an Escherichia coli urinary tract infection. Among 33 infants with bloody stools across the groups, 14 cases were determined to have been related to the vaccine. One case of intussusception occurring 91 days after the last dose was classified as unrelated to the vaccine.
The research was funded by the National Institute of Allergy and Infectious Diseases, the National Institutes of Health, and the US Department of Health and Human Services. Dr. Libster and her colleagues all reported some kind of relationship with a variety of companies including Merck, Novartis, bioCSL, and others. Dr. Turley also holds publicly traded Abbott and Pfizer stock, and Ms. McNeal has laboratory service agreements with Merck and GSK.
Expert opinion has led the American Academy of Pediatrics’ Committee on Infectious Diseases to advise providers that timely completion of immunization with any available licensed product is better than delaying immunization for a specific product. The article by Libster et al. in this issue of Pediatrics supports this principle and reassures us that for rotavirus vaccines, immunization with a mixed series of vaccines is safe and results in an immune response that is noninferior to that generated by immunization with any single product.
Importantly, the study met the enrollment goals for statistical power. The proportion of children seropositive for at least one vaccine antigen was high and was similar for all vaccine combinations. All combinations of vaccine were well tolerated, and serious adverse events were rare with any of the vaccine combinations and, in the majority of cases, unrelated to vaccine administration.
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Dr. Yvonne Maldonado |
The findings of Libster et al, in addition to demonstrating the efficacy of multiple vaccine combinations for rotavirus, also serve as a reminder of the importance of the infrastructures of the National Institutes of Health–supported Vaccine and Treatment Evaluation Units and the Clinical and Translational Science Awards in supporting the health of children. Without these federally funded resources, it is unlikely that the evaluation of multiple rotavirus vaccine combinations would have been conducted. Individual vaccine manufacturers have little or no incentive to test their licensed products in combination with those of other manufacturers. As child health advocates, we regularly encourage the use of vaccines. We must remember that our advocacy should also include working to ensure that the research infrastructure of the nation is strong and that adequate resources are devoted to investigations that will benefit the health of children.
These comments have been edited from a commentary accompanying the study (Pediatrics. 2016 Jan 28. doi: 10.1542/peds.2015-3618). Dr. Carrie L. Byington is with the University of Utah, Salt Lake City, department of pediatrics and Dr. Yvonne Maldonado is with the Stanford (Calif.) University department of pediatrics. Dr. Byington is supported by an H.A. and Edna Benning Presidential Endowment and the National Center for Advancing Translational Sciences. Dr. Maldonado is supported by the Bill and Melinda Gates Foundation and the National Institutes of Health. Dr. Byington has intellectual property in and receives royalties from BioFire Diagnostics and Dr. Maldonado is a member of a data safety monitoring board for Pfizer.
Expert opinion has led the American Academy of Pediatrics’ Committee on Infectious Diseases to advise providers that timely completion of immunization with any available licensed product is better than delaying immunization for a specific product. The article by Libster et al. in this issue of Pediatrics supports this principle and reassures us that for rotavirus vaccines, immunization with a mixed series of vaccines is safe and results in an immune response that is noninferior to that generated by immunization with any single product.
Importantly, the study met the enrollment goals for statistical power. The proportion of children seropositive for at least one vaccine antigen was high and was similar for all vaccine combinations. All combinations of vaccine were well tolerated, and serious adverse events were rare with any of the vaccine combinations and, in the majority of cases, unrelated to vaccine administration.
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|
Dr. Yvonne Maldonado |
The findings of Libster et al, in addition to demonstrating the efficacy of multiple vaccine combinations for rotavirus, also serve as a reminder of the importance of the infrastructures of the National Institutes of Health–supported Vaccine and Treatment Evaluation Units and the Clinical and Translational Science Awards in supporting the health of children. Without these federally funded resources, it is unlikely that the evaluation of multiple rotavirus vaccine combinations would have been conducted. Individual vaccine manufacturers have little or no incentive to test their licensed products in combination with those of other manufacturers. As child health advocates, we regularly encourage the use of vaccines. We must remember that our advocacy should also include working to ensure that the research infrastructure of the nation is strong and that adequate resources are devoted to investigations that will benefit the health of children.
These comments have been edited from a commentary accompanying the study (Pediatrics. 2016 Jan 28. doi: 10.1542/peds.2015-3618). Dr. Carrie L. Byington is with the University of Utah, Salt Lake City, department of pediatrics and Dr. Yvonne Maldonado is with the Stanford (Calif.) University department of pediatrics. Dr. Byington is supported by an H.A. and Edna Benning Presidential Endowment and the National Center for Advancing Translational Sciences. Dr. Maldonado is supported by the Bill and Melinda Gates Foundation and the National Institutes of Health. Dr. Byington has intellectual property in and receives royalties from BioFire Diagnostics and Dr. Maldonado is a member of a data safety monitoring board for Pfizer.
Expert opinion has led the American Academy of Pediatrics’ Committee on Infectious Diseases to advise providers that timely completion of immunization with any available licensed product is better than delaying immunization for a specific product. The article by Libster et al. in this issue of Pediatrics supports this principle and reassures us that for rotavirus vaccines, immunization with a mixed series of vaccines is safe and results in an immune response that is noninferior to that generated by immunization with any single product.
Importantly, the study met the enrollment goals for statistical power. The proportion of children seropositive for at least one vaccine antigen was high and was similar for all vaccine combinations. All combinations of vaccine were well tolerated, and serious adverse events were rare with any of the vaccine combinations and, in the majority of cases, unrelated to vaccine administration.
|
|
Dr. Yvonne Maldonado |
The findings of Libster et al, in addition to demonstrating the efficacy of multiple vaccine combinations for rotavirus, also serve as a reminder of the importance of the infrastructures of the National Institutes of Health–supported Vaccine and Treatment Evaluation Units and the Clinical and Translational Science Awards in supporting the health of children. Without these federally funded resources, it is unlikely that the evaluation of multiple rotavirus vaccine combinations would have been conducted. Individual vaccine manufacturers have little or no incentive to test their licensed products in combination with those of other manufacturers. As child health advocates, we regularly encourage the use of vaccines. We must remember that our advocacy should also include working to ensure that the research infrastructure of the nation is strong and that adequate resources are devoted to investigations that will benefit the health of children.
These comments have been edited from a commentary accompanying the study (Pediatrics. 2016 Jan 28. doi: 10.1542/peds.2015-3618). Dr. Carrie L. Byington is with the University of Utah, Salt Lake City, department of pediatrics and Dr. Yvonne Maldonado is with the Stanford (Calif.) University department of pediatrics. Dr. Byington is supported by an H.A. and Edna Benning Presidential Endowment and the National Center for Advancing Translational Sciences. Dr. Maldonado is supported by the Bill and Melinda Gates Foundation and the National Institutes of Health. Dr. Byington has intellectual property in and receives royalties from BioFire Diagnostics and Dr. Maldonado is a member of a data safety monitoring board for Pfizer.
Mixing the RotaTeq and Rotarix rotavirus vaccines schedules resulted in noninferior immunogenicity compared with using only one vaccine schedule, found a new multicenter, open-label study. Safety profiles were also similar among mixed-vaccine and single-vaccine groups, according to Dr. Romina Libster of Vanderbilt University, Nashville, Tenn., and her associates.
“These encouraging data are supported by an earlier study involving precursors of both vaccines and natural rotavirus infections,” wrote Dr. Libster and her colleagues online (Pediatrics. 2016 Jan 28. doi: 10.1542/peds.2015-2603).
The researchers randomly assigned 1,393 healthy infants who were between 6 and 14 weeks old to receive one of five different rotavirus vaccine schedules. The children, enrolled from March 2011 through September 2013, either received all doses from one vaccine or a mixture of the two different rotavirus vaccines, concurrently with other routine immunizations, accordingly:
• 244 children received three doses of RotaTeq (RV5), a live, oral vaccine containing a combination of five human-bovine reassortant rotaviruses.
• 330 children received two doses of Rotarix (RV1), a live-attenuated human rotavirus vaccine from a single human strain.
• 250 children received one dose of RotaTeq, followed by two doses of Rotarix.
• 240 children received two consecutive doses of RotaTeq followed by a dose of Rotarix.
• 329 children received one dose of Rotarix, followed by two consecutive doses of RotaTeq.
Among the 1,236 infants remaining in the study at follow-up, 77%-96% of them across the study groups attained seropositivity defined as IgA greater than or equal to 20 U/mL against at least one vaccine antigen 1 month after the last vaccine dose. Each of the mixed schedules was noninferior to each of the single-vaccine–type schedules.
In fact, a significantly greater proportion of infants receiving one Rotarix vaccine dose followed by two RotaTeq doses achieved seropositivity against both WC3 and 89-12, compared with those receiving two Rotarix doses. Similarly, infants receiving two doses of RotaTeq and one dose of Rotarix (in either order) had higher average titers against WC3 and 89-12 than infants in either of the single-vaccine groups.
“As this study was not aimed to evaluate vaccine efficacy and there is a gap of knowledge regarding a precise correlate of protection for rotavirus vaccine, the clinical relevance of the differences in immunogenicity is unclear,” the authors wrote.
No significant differences in rates of fever, diarrhea, or vomiting occurred when comparing the RV5-RV1-RV1 and RV5-RV5-RV1 groups to the single RotaTeq (RV4) group. The RV1-RV5-RV5 group, however, showed significantly more fever and vomiting than did the single Rotarix group.
“However, when the associations between group and presence of solicited symptoms were stratified by vaccine dose, there were no statistically significant differences between the two groups for the first or second doses of rotavirus vaccine,” the authors wrote.
The most commonly reported adverse event was irritability. Of 70 infants hospitalized during the study, only one case was linked to the vaccine: a 2-month-old girl receiving two doses of Rotarix and diagnosed after the first dose with gastroenteritis concurrent with an Escherichia coli urinary tract infection. Among 33 infants with bloody stools across the groups, 14 cases were determined to have been related to the vaccine. One case of intussusception occurring 91 days after the last dose was classified as unrelated to the vaccine.
The research was funded by the National Institute of Allergy and Infectious Diseases, the National Institutes of Health, and the US Department of Health and Human Services. Dr. Libster and her colleagues all reported some kind of relationship with a variety of companies including Merck, Novartis, bioCSL, and others. Dr. Turley also holds publicly traded Abbott and Pfizer stock, and Ms. McNeal has laboratory service agreements with Merck and GSK.
Mixing the RotaTeq and Rotarix rotavirus vaccines schedules resulted in noninferior immunogenicity compared with using only one vaccine schedule, found a new multicenter, open-label study. Safety profiles were also similar among mixed-vaccine and single-vaccine groups, according to Dr. Romina Libster of Vanderbilt University, Nashville, Tenn., and her associates.
“These encouraging data are supported by an earlier study involving precursors of both vaccines and natural rotavirus infections,” wrote Dr. Libster and her colleagues online (Pediatrics. 2016 Jan 28. doi: 10.1542/peds.2015-2603).
The researchers randomly assigned 1,393 healthy infants who were between 6 and 14 weeks old to receive one of five different rotavirus vaccine schedules. The children, enrolled from March 2011 through September 2013, either received all doses from one vaccine or a mixture of the two different rotavirus vaccines, concurrently with other routine immunizations, accordingly:
• 244 children received three doses of RotaTeq (RV5), a live, oral vaccine containing a combination of five human-bovine reassortant rotaviruses.
• 330 children received two doses of Rotarix (RV1), a live-attenuated human rotavirus vaccine from a single human strain.
• 250 children received one dose of RotaTeq, followed by two doses of Rotarix.
• 240 children received two consecutive doses of RotaTeq followed by a dose of Rotarix.
• 329 children received one dose of Rotarix, followed by two consecutive doses of RotaTeq.
Among the 1,236 infants remaining in the study at follow-up, 77%-96% of them across the study groups attained seropositivity defined as IgA greater than or equal to 20 U/mL against at least one vaccine antigen 1 month after the last vaccine dose. Each of the mixed schedules was noninferior to each of the single-vaccine–type schedules.
In fact, a significantly greater proportion of infants receiving one Rotarix vaccine dose followed by two RotaTeq doses achieved seropositivity against both WC3 and 89-12, compared with those receiving two Rotarix doses. Similarly, infants receiving two doses of RotaTeq and one dose of Rotarix (in either order) had higher average titers against WC3 and 89-12 than infants in either of the single-vaccine groups.
“As this study was not aimed to evaluate vaccine efficacy and there is a gap of knowledge regarding a precise correlate of protection for rotavirus vaccine, the clinical relevance of the differences in immunogenicity is unclear,” the authors wrote.
No significant differences in rates of fever, diarrhea, or vomiting occurred when comparing the RV5-RV1-RV1 and RV5-RV5-RV1 groups to the single RotaTeq (RV4) group. The RV1-RV5-RV5 group, however, showed significantly more fever and vomiting than did the single Rotarix group.
“However, when the associations between group and presence of solicited symptoms were stratified by vaccine dose, there were no statistically significant differences between the two groups for the first or second doses of rotavirus vaccine,” the authors wrote.
The most commonly reported adverse event was irritability. Of 70 infants hospitalized during the study, only one case was linked to the vaccine: a 2-month-old girl receiving two doses of Rotarix and diagnosed after the first dose with gastroenteritis concurrent with an Escherichia coli urinary tract infection. Among 33 infants with bloody stools across the groups, 14 cases were determined to have been related to the vaccine. One case of intussusception occurring 91 days after the last dose was classified as unrelated to the vaccine.
The research was funded by the National Institute of Allergy and Infectious Diseases, the National Institutes of Health, and the US Department of Health and Human Services. Dr. Libster and her colleagues all reported some kind of relationship with a variety of companies including Merck, Novartis, bioCSL, and others. Dr. Turley also holds publicly traded Abbott and Pfizer stock, and Ms. McNeal has laboratory service agreements with Merck and GSK.
FROM PEDIATRICS
Key clinical point: Mixing rotavirus vaccine schedules is safe and comparable to single vaccine schedules.
Major finding: 77%-96% of infants receiving single vaccine schedules or a mixed schedule achieved seropositivity.
Data source: The findings are based on a randomized, multicenter, open-label study involving 1,393 children between 6 and 14 weeks old, enrolled from March 2011 through September 2013 and randomized to receive one of five different rotavirus vaccine schedules.
Disclosures: The research was funded by the National Institute of Allergy and Infectious Diseases, the National Institutes of Health, and the U.S. Department of Health & Human Services. Dr. Libster and her colleagues all reported some kind of relationship with a variety of companies including Merck, Novartis, bioCSL, and others. Dr. Turley also holds publicly traded Abbott and Pfizer stock, and Ms. McNeal has laboratory service agreements with Merck and GSK.
Antidepressant use in children, adolescents may double aggression, suicidality risk
Children and adolescents who take certain SSRIs and SNRIs appear to be at double the risk of aggression and suicidality, however, no such associations are found in adults, according to results of a systematic review and meta-analysis published online Jan. 27.
Those are some of the results of the review and meta-analysis involving more than 18,500 patients conducted by Tarang Sharma of the Nordic Cochrane Centre in Copenhagen, and her colleagues of five antidepressants. The researchers sought to assess the associations between selective serotonin reuptake inhibitors and four outcomes: mortality, suicidality, aggression, and akathisia. Their report was published online in BMJ (2016 Jan 27. doi: 10.1136/bmj.i65).
Ms. Sharma and her colleagues analyzed 68 clinical study reports involving 70 trials investigating duloxetine, fluoxetine, paroxetine, sertraline, and venlafaxine. Of the included trials, 11 involved children and adolescents, and 63% (n = 44) excluded patients at risk for suicide.
Overall, the researchers found no significant differences in akathisia (odds ratio, 2.04; 95% confidence interval, 0.93-4.48), suicidality (OR, 1.21; 95% CI, 0.81-1.74), or mortality (OR, 1.28; 95% CI, 0.40-4.06). However, they did find an association with aggressive behavior (OR, 1.93; 95% CI, 1.26-2.95).
When they separated the adult data from those of younger patients, however, they found that children and adolescents had double the risk of aggression (OR 2.79, 95% CI: 1.62-4.81) and suicidality (OR, 2.39; 95% CI, 1.31-4.33). The risk of akathisia was lower (OR, 2.19; 95% CI, 0.48-9.65). Data for adults did not demonstrate a significant increase in aggression (OR, 1.09; 95% CI, 0.55-2.14), suicidality (OR, 0.81; 95% 0.51-1.28), or akathisia (OR, 2.00; 95% CI, 0.79-5.04).
The authors noted several limitations in the trials, such as insufficient lead-in periods. In addition, there were inconsistencies between the trials in how the events were coded. Further, 46% of the trials included in the analysis did not note which coding dictionary was used. The authors point out that the limitations of the trials in terms of clinical study reports “may have led to serious underestimation of the harms” and that there is still uncertainty of the true risks.
The Laura and John Arnold Foundation funded the study. The authors report no disclosures.
The analysis by Tarang Sharma and her colleagues suggests that clinical study reports probably underestimate the possible negative effects of antidepressants, Dr. Joanna Moncrieff wrote in an accompanying editorial.
“To reevaluate antidepressants properly, we need access to original data from trials, but we also need research that clarifies the whole range of antidepressant-induced … alterations” after acute treatment, use, and withdrawal, she wrote.
Dr. Moncrieff, a senior lecturer in the division of psychiatry at the University College London, is a cochair of the Critical Psychiatry Network. Her editorial also was published in BMJ online (2016 Jan 27. doi: 10.1136/bmj.i217.
The analysis by Tarang Sharma and her colleagues suggests that clinical study reports probably underestimate the possible negative effects of antidepressants, Dr. Joanna Moncrieff wrote in an accompanying editorial.
“To reevaluate antidepressants properly, we need access to original data from trials, but we also need research that clarifies the whole range of antidepressant-induced … alterations” after acute treatment, use, and withdrawal, she wrote.
Dr. Moncrieff, a senior lecturer in the division of psychiatry at the University College London, is a cochair of the Critical Psychiatry Network. Her editorial also was published in BMJ online (2016 Jan 27. doi: 10.1136/bmj.i217.
The analysis by Tarang Sharma and her colleagues suggests that clinical study reports probably underestimate the possible negative effects of antidepressants, Dr. Joanna Moncrieff wrote in an accompanying editorial.
“To reevaluate antidepressants properly, we need access to original data from trials, but we also need research that clarifies the whole range of antidepressant-induced … alterations” after acute treatment, use, and withdrawal, she wrote.
Dr. Moncrieff, a senior lecturer in the division of psychiatry at the University College London, is a cochair of the Critical Psychiatry Network. Her editorial also was published in BMJ online (2016 Jan 27. doi: 10.1136/bmj.i217.
Children and adolescents who take certain SSRIs and SNRIs appear to be at double the risk of aggression and suicidality, however, no such associations are found in adults, according to results of a systematic review and meta-analysis published online Jan. 27.
Those are some of the results of the review and meta-analysis involving more than 18,500 patients conducted by Tarang Sharma of the Nordic Cochrane Centre in Copenhagen, and her colleagues of five antidepressants. The researchers sought to assess the associations between selective serotonin reuptake inhibitors and four outcomes: mortality, suicidality, aggression, and akathisia. Their report was published online in BMJ (2016 Jan 27. doi: 10.1136/bmj.i65).
Ms. Sharma and her colleagues analyzed 68 clinical study reports involving 70 trials investigating duloxetine, fluoxetine, paroxetine, sertraline, and venlafaxine. Of the included trials, 11 involved children and adolescents, and 63% (n = 44) excluded patients at risk for suicide.
Overall, the researchers found no significant differences in akathisia (odds ratio, 2.04; 95% confidence interval, 0.93-4.48), suicidality (OR, 1.21; 95% CI, 0.81-1.74), or mortality (OR, 1.28; 95% CI, 0.40-4.06). However, they did find an association with aggressive behavior (OR, 1.93; 95% CI, 1.26-2.95).
When they separated the adult data from those of younger patients, however, they found that children and adolescents had double the risk of aggression (OR 2.79, 95% CI: 1.62-4.81) and suicidality (OR, 2.39; 95% CI, 1.31-4.33). The risk of akathisia was lower (OR, 2.19; 95% CI, 0.48-9.65). Data for adults did not demonstrate a significant increase in aggression (OR, 1.09; 95% CI, 0.55-2.14), suicidality (OR, 0.81; 95% 0.51-1.28), or akathisia (OR, 2.00; 95% CI, 0.79-5.04).
The authors noted several limitations in the trials, such as insufficient lead-in periods. In addition, there were inconsistencies between the trials in how the events were coded. Further, 46% of the trials included in the analysis did not note which coding dictionary was used. The authors point out that the limitations of the trials in terms of clinical study reports “may have led to serious underestimation of the harms” and that there is still uncertainty of the true risks.
The Laura and John Arnold Foundation funded the study. The authors report no disclosures.
Children and adolescents who take certain SSRIs and SNRIs appear to be at double the risk of aggression and suicidality, however, no such associations are found in adults, according to results of a systematic review and meta-analysis published online Jan. 27.
Those are some of the results of the review and meta-analysis involving more than 18,500 patients conducted by Tarang Sharma of the Nordic Cochrane Centre in Copenhagen, and her colleagues of five antidepressants. The researchers sought to assess the associations between selective serotonin reuptake inhibitors and four outcomes: mortality, suicidality, aggression, and akathisia. Their report was published online in BMJ (2016 Jan 27. doi: 10.1136/bmj.i65).
Ms. Sharma and her colleagues analyzed 68 clinical study reports involving 70 trials investigating duloxetine, fluoxetine, paroxetine, sertraline, and venlafaxine. Of the included trials, 11 involved children and adolescents, and 63% (n = 44) excluded patients at risk for suicide.
Overall, the researchers found no significant differences in akathisia (odds ratio, 2.04; 95% confidence interval, 0.93-4.48), suicidality (OR, 1.21; 95% CI, 0.81-1.74), or mortality (OR, 1.28; 95% CI, 0.40-4.06). However, they did find an association with aggressive behavior (OR, 1.93; 95% CI, 1.26-2.95).
When they separated the adult data from those of younger patients, however, they found that children and adolescents had double the risk of aggression (OR 2.79, 95% CI: 1.62-4.81) and suicidality (OR, 2.39; 95% CI, 1.31-4.33). The risk of akathisia was lower (OR, 2.19; 95% CI, 0.48-9.65). Data for adults did not demonstrate a significant increase in aggression (OR, 1.09; 95% CI, 0.55-2.14), suicidality (OR, 0.81; 95% 0.51-1.28), or akathisia (OR, 2.00; 95% CI, 0.79-5.04).
The authors noted several limitations in the trials, such as insufficient lead-in periods. In addition, there were inconsistencies between the trials in how the events were coded. Further, 46% of the trials included in the analysis did not note which coding dictionary was used. The authors point out that the limitations of the trials in terms of clinical study reports “may have led to serious underestimation of the harms” and that there is still uncertainty of the true risks.
The Laura and John Arnold Foundation funded the study. The authors report no disclosures.
FROM BMJ
Key clinical point: Meta-analysis finds increased risk of suicidality and aggression in children and adolescents taking certain antidepressants.
Major finding: Children and adolescents had double the risk of aggression (OR, 2.79; 95% CI, 1.62-4.81) and suicidality (OR, 2.39; 95% CI, 1.31-4.33).
Data source: A systematic review and meta-analysis of clinical study reports for five antidepressants to assess potential harms associated with SSRIs and SNRIs.
Disclosures: The Laura and John Arnold Foundation funded the study. The authors report no disclosures.
The newest ‘rage’: disruptive mood dysregulation disorder
Outbursts by children when frustrated or when asked to “do something they don’t want to do” are among the most common behavioral complaints voiced by parents. But behavioral outbursts, beyond the typical tantrums of children up to age 4 years, can be signs of very severe mental health disorders and are the most common reason for psychiatric admission (50%-60%).
While behavioral dysregulation is undeniably a huge problem for families, there has been an unreasonable 40-fold rise in diagnosis of bipolar disorder from 1994 to 2003, and 48% were prescribed atypical neuroleptics – medications with serious side effects. In response to this overdiagnosis as bipolar disorder, in 2013 the DSM-5 created a new diagnosis called disruptive mood dysregulation disorder (DMDD) to differentiate children who experience explosive outbursts who have a different outcome. This new classification includes children aged 6-12 years with persistent irritability most of the time, nearly every day, lasting at least 12 months and starting before age 10 years. DMDD diagnosis is not used after age 18 years.
To be diagnosed, the child has to have frequent, severe temper outbursts “grossly out of proportion” to the situation, averaging at least three times per week. The outbursts can be verbal or physical aggression to people, things, or themselves. While tantrums can be severe in children with delayed development, for the DMDD diagnosis these behaviors must be inconsistent with developmental level and must occur in at least two settings, and in one setting it must be severe. While outbursts are common, only half of children in one study of severe tantrum behavior in 5- to 9-year-olds also had the required persistent irritability.
If this does sound a lot like bipolar disorder so far, you are right. So what is different? DMDD has a prevalence of 2%-5% and occurs mostly in boys, whereas bipolar disorder affects boys and girls equally and affects less than 1% prior to adolescence.
The key features distinguishing DMDD from bipolar disorder are lack of an episodic nature to the irritability and lack of mania. Irritability in DMDD has to be persistently present with breaks of no more than 3 consecutive months in the defining 12-month period. There also cannot be any more than 1 day of the elevated mood features of mania or hypomania. Identifying mania is the hardest part, even in diagnosing adult bipolar, where it occurs only 1% of the year, much less in children who are generally lively! Hypomania, while less intense than mania, is when the person is energetic, talkative, and confident to an extreme extent, often with a flight of creative ideas. Excitement over birthdays or Christmas specifically does not count! So getting this history has to be done carefully, generally by a mental health professional, to make the distinction.
Interestingly, DMDD is not diagnosed when outbursts and irritability are better explained by autism spectrum disorder, separation anxiety disorder, or PTSD. To me, these exclusions point out the importance of sorting out the “set conditions” for all problematic behaviors, not always an easy task. Symptoms of autism in high functioning individuals can be quite subtle. Was the upset from change in a rigid routine known only to the child? Were sensory stimuli such as loud noises intolerable to this child? Was a nonverbal signal of a peer mistaken as a threat? While violent outbursts precipitated by these factors would still be considered “grossly out of proportion to the situation” for a typical child, they are not uncommon in atypical children. Similarly, children with separation anxiety disorder experience a high level of threat from even thinking about being apart from their caregivers, setting them up for alarm by situations other children would not find difficult.
The American Academy of Pediatrics emphasizes the need to assess all children for a history of psychological trauma. Traumas are quite common, and their sequelae affect many aspects of the child’s life; in the case of outbursts, it is emotional resilience that is impaired. As for all DSM-5 diagnoses, DMDD is not diagnosed when the irritability is due to physiological effects of a substance (e.g. steroids) or another medical or neurological disorder. Children with chronic pain conditions such as rheumatoid arthritis or sickle cell usually cope remarkably well, but when they don’t, their irritability should not be considered a mental health disorder. More commonly, sleep debt can produce chronic irritability and always should be assessed.
When coaching families about outbursts, I work to help them recognize that the child is not just angry, but very distressed. While “typical” tantrums last 1-5 minutes and show a rise then decline in intensity of the anger and distress, anger outbursts are longer and have an initial short and rapid burst of anger that then declines over the duration of the outburst, and with a steady but lower level of distress throughout.
The option to hug and verbally console the child’s distress is sometimes effective and does not reinforce the behavior unless the parent also yields to demands. But once outbursts begin, I liken them to a bomb going off – there is no intervention possible then. Instead, the task of the family, and over time that of the child, is to recognize and better manage the triggers.
Dr. Ross Greene, in his book, “The Explosive Child: A New Approach for Understanding and Parenting Easily Frustrated, Chronically Inflexible Children,” asserts that the child’s anger and distress can be interpreted as frustration from a gap in skills. This has treatment implications for identifying, educating about, and ameliorating the child’s weaknesses (deficits in understanding, communication, emotion regulation, flexibility or performance; or excess jealousy or hypersensitivity), and coaching parents to recognize, acknowledge, and avoid stressing these areas, if possible. I coach families to give points to the child for progressive little steps toward being able to recognize, verbalize, and inhibit outbursts with a reward system for the points. This helps put the parents and child “on the same team” in working on improving these skills.
Research on children with DMDD indicates that they show less positive affect when winning a “fixed” video game and are less able to suppress negative affect when losing. (Don’t forget to examine the role of real video games as precipitants of tantrums and contingently remove them!) Threshold for upset is lower and the degree of the upsets less well handled by children with DMDD.
In another study, when presented with a series of ambiguous facial expressions, children with DMDD were more likely to see anger in the faces than were controls. One hopeful result was that they could be taught to shift their perceptions significantly away from seeing anger, also reducing irritability and resulting in functional MRI changes. Such hostile bias attribution (tending to see threat) is well known to predispose to aggression. Cognitive behavioral therapy, the most effective counseling intervention, similarly teaches children to rethink their own negative thoughts before acting.
If irritability and rages were not enough, most children with DMDD have other psychiatric disorders; 39% having two, and 51% three or more (J Child Adolesc Psychopharmacol. 2013 Nov;23[9]:588-96). If not for the DMDD diagnosis, 82% would meet criteria for oppositional defiant disorder (ODD). The other common comorbidities are attention-deficit/hyperactivity disorder (ADHD) (74.5%), anxiety disorders (49.0%), and depression that is not major depressive disorder (MDD)(33.3%). When MDD is present, that diagnosis takes precedence. One cannot diagnose ODD, intermittent explosive disorder, or bipolar disorder along with DMDD, conditions from which it is intended to differentiate. Each of these comorbid disorders can be difficult to manage alone much less in combination, making DMDD a disorder deserving diagnosis and treatment by a mental health professional.
One of the main reasons DMDD was created is that children with these features go on to depressive or anxiety disorder in adolescence, not bipolar disorder.
While there is no treatment specific to DMDD, the depression component and prognosis suggest use of SSRIs, in addition to psychosocial therapies, and stimulants for the comorbid ADHD. Unfortunately, these two classes of medication are relatively contraindicated in bipolar disorder because they can lead to treatment-induced episodic mania (TEM). TEM occurs twice as often with antidepressants compared with stimulants (44% vs. 18%) in children with bipolar disorder (J Affect Disord. 2004 Oct 1;82[1]:149-58). Getting the diagnosis correct is, therefore, of great importance when medication is considered.
Approaches such as behavior modification, family therapy, and inpatient treatment can be effective for chronic irritability and aggression. Stimulant treatment of comorbid ADHD can decrease aggression and irritability. Alpha agonists such as guanfacine or clonidine also can help. In cases of partial improvement, adding either risperidone or divalproex may further decrease aggression in ADHD. In refractory aggression, risperidone has the best evidence. The Affective Reactivity Index or Outburst Monitoring Scale can be helpful in assessing severity and monitoring outcomes.
While a prognosis for depression rather than bipolar disorder sounds like a plus, in a longitudinal study, adults who had DMDD as children had worse outcomes, including being more likely to have adverse health outcomes (smoking, sexually transmitted infection), police contact, and low educational attainment, and being more likely to live in poverty, compared with controls who had other psychiatric disorders. While DMDD is a new and different diagnosis, it is similar to bipolar in having a potential course of life disruption, dangerous behaviors, suicide risk, and hospitalization.
Dr. Howard is assistant professor of pediatrics at the Johns Hopkins University, Baltimore, and creator of CHADIS (www.CHADIS.com). She had no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to Frontline. E-mail her at pdnews@frontlinemedcom.com.
Outbursts by children when frustrated or when asked to “do something they don’t want to do” are among the most common behavioral complaints voiced by parents. But behavioral outbursts, beyond the typical tantrums of children up to age 4 years, can be signs of very severe mental health disorders and are the most common reason for psychiatric admission (50%-60%).
While behavioral dysregulation is undeniably a huge problem for families, there has been an unreasonable 40-fold rise in diagnosis of bipolar disorder from 1994 to 2003, and 48% were prescribed atypical neuroleptics – medications with serious side effects. In response to this overdiagnosis as bipolar disorder, in 2013 the DSM-5 created a new diagnosis called disruptive mood dysregulation disorder (DMDD) to differentiate children who experience explosive outbursts who have a different outcome. This new classification includes children aged 6-12 years with persistent irritability most of the time, nearly every day, lasting at least 12 months and starting before age 10 years. DMDD diagnosis is not used after age 18 years.
To be diagnosed, the child has to have frequent, severe temper outbursts “grossly out of proportion” to the situation, averaging at least three times per week. The outbursts can be verbal or physical aggression to people, things, or themselves. While tantrums can be severe in children with delayed development, for the DMDD diagnosis these behaviors must be inconsistent with developmental level and must occur in at least two settings, and in one setting it must be severe. While outbursts are common, only half of children in one study of severe tantrum behavior in 5- to 9-year-olds also had the required persistent irritability.
If this does sound a lot like bipolar disorder so far, you are right. So what is different? DMDD has a prevalence of 2%-5% and occurs mostly in boys, whereas bipolar disorder affects boys and girls equally and affects less than 1% prior to adolescence.
The key features distinguishing DMDD from bipolar disorder are lack of an episodic nature to the irritability and lack of mania. Irritability in DMDD has to be persistently present with breaks of no more than 3 consecutive months in the defining 12-month period. There also cannot be any more than 1 day of the elevated mood features of mania or hypomania. Identifying mania is the hardest part, even in diagnosing adult bipolar, where it occurs only 1% of the year, much less in children who are generally lively! Hypomania, while less intense than mania, is when the person is energetic, talkative, and confident to an extreme extent, often with a flight of creative ideas. Excitement over birthdays or Christmas specifically does not count! So getting this history has to be done carefully, generally by a mental health professional, to make the distinction.
Interestingly, DMDD is not diagnosed when outbursts and irritability are better explained by autism spectrum disorder, separation anxiety disorder, or PTSD. To me, these exclusions point out the importance of sorting out the “set conditions” for all problematic behaviors, not always an easy task. Symptoms of autism in high functioning individuals can be quite subtle. Was the upset from change in a rigid routine known only to the child? Were sensory stimuli such as loud noises intolerable to this child? Was a nonverbal signal of a peer mistaken as a threat? While violent outbursts precipitated by these factors would still be considered “grossly out of proportion to the situation” for a typical child, they are not uncommon in atypical children. Similarly, children with separation anxiety disorder experience a high level of threat from even thinking about being apart from their caregivers, setting them up for alarm by situations other children would not find difficult.
The American Academy of Pediatrics emphasizes the need to assess all children for a history of psychological trauma. Traumas are quite common, and their sequelae affect many aspects of the child’s life; in the case of outbursts, it is emotional resilience that is impaired. As for all DSM-5 diagnoses, DMDD is not diagnosed when the irritability is due to physiological effects of a substance (e.g. steroids) or another medical or neurological disorder. Children with chronic pain conditions such as rheumatoid arthritis or sickle cell usually cope remarkably well, but when they don’t, their irritability should not be considered a mental health disorder. More commonly, sleep debt can produce chronic irritability and always should be assessed.
When coaching families about outbursts, I work to help them recognize that the child is not just angry, but very distressed. While “typical” tantrums last 1-5 minutes and show a rise then decline in intensity of the anger and distress, anger outbursts are longer and have an initial short and rapid burst of anger that then declines over the duration of the outburst, and with a steady but lower level of distress throughout.
The option to hug and verbally console the child’s distress is sometimes effective and does not reinforce the behavior unless the parent also yields to demands. But once outbursts begin, I liken them to a bomb going off – there is no intervention possible then. Instead, the task of the family, and over time that of the child, is to recognize and better manage the triggers.
Dr. Ross Greene, in his book, “The Explosive Child: A New Approach for Understanding and Parenting Easily Frustrated, Chronically Inflexible Children,” asserts that the child’s anger and distress can be interpreted as frustration from a gap in skills. This has treatment implications for identifying, educating about, and ameliorating the child’s weaknesses (deficits in understanding, communication, emotion regulation, flexibility or performance; or excess jealousy or hypersensitivity), and coaching parents to recognize, acknowledge, and avoid stressing these areas, if possible. I coach families to give points to the child for progressive little steps toward being able to recognize, verbalize, and inhibit outbursts with a reward system for the points. This helps put the parents and child “on the same team” in working on improving these skills.
Research on children with DMDD indicates that they show less positive affect when winning a “fixed” video game and are less able to suppress negative affect when losing. (Don’t forget to examine the role of real video games as precipitants of tantrums and contingently remove them!) Threshold for upset is lower and the degree of the upsets less well handled by children with DMDD.
In another study, when presented with a series of ambiguous facial expressions, children with DMDD were more likely to see anger in the faces than were controls. One hopeful result was that they could be taught to shift their perceptions significantly away from seeing anger, also reducing irritability and resulting in functional MRI changes. Such hostile bias attribution (tending to see threat) is well known to predispose to aggression. Cognitive behavioral therapy, the most effective counseling intervention, similarly teaches children to rethink their own negative thoughts before acting.
If irritability and rages were not enough, most children with DMDD have other psychiatric disorders; 39% having two, and 51% three or more (J Child Adolesc Psychopharmacol. 2013 Nov;23[9]:588-96). If not for the DMDD diagnosis, 82% would meet criteria for oppositional defiant disorder (ODD). The other common comorbidities are attention-deficit/hyperactivity disorder (ADHD) (74.5%), anxiety disorders (49.0%), and depression that is not major depressive disorder (MDD)(33.3%). When MDD is present, that diagnosis takes precedence. One cannot diagnose ODD, intermittent explosive disorder, or bipolar disorder along with DMDD, conditions from which it is intended to differentiate. Each of these comorbid disorders can be difficult to manage alone much less in combination, making DMDD a disorder deserving diagnosis and treatment by a mental health professional.
One of the main reasons DMDD was created is that children with these features go on to depressive or anxiety disorder in adolescence, not bipolar disorder.
While there is no treatment specific to DMDD, the depression component and prognosis suggest use of SSRIs, in addition to psychosocial therapies, and stimulants for the comorbid ADHD. Unfortunately, these two classes of medication are relatively contraindicated in bipolar disorder because they can lead to treatment-induced episodic mania (TEM). TEM occurs twice as often with antidepressants compared with stimulants (44% vs. 18%) in children with bipolar disorder (J Affect Disord. 2004 Oct 1;82[1]:149-58). Getting the diagnosis correct is, therefore, of great importance when medication is considered.
Approaches such as behavior modification, family therapy, and inpatient treatment can be effective for chronic irritability and aggression. Stimulant treatment of comorbid ADHD can decrease aggression and irritability. Alpha agonists such as guanfacine or clonidine also can help. In cases of partial improvement, adding either risperidone or divalproex may further decrease aggression in ADHD. In refractory aggression, risperidone has the best evidence. The Affective Reactivity Index or Outburst Monitoring Scale can be helpful in assessing severity and monitoring outcomes.
While a prognosis for depression rather than bipolar disorder sounds like a plus, in a longitudinal study, adults who had DMDD as children had worse outcomes, including being more likely to have adverse health outcomes (smoking, sexually transmitted infection), police contact, and low educational attainment, and being more likely to live in poverty, compared with controls who had other psychiatric disorders. While DMDD is a new and different diagnosis, it is similar to bipolar in having a potential course of life disruption, dangerous behaviors, suicide risk, and hospitalization.
Dr. Howard is assistant professor of pediatrics at the Johns Hopkins University, Baltimore, and creator of CHADIS (www.CHADIS.com). She had no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to Frontline. E-mail her at pdnews@frontlinemedcom.com.
Outbursts by children when frustrated or when asked to “do something they don’t want to do” are among the most common behavioral complaints voiced by parents. But behavioral outbursts, beyond the typical tantrums of children up to age 4 years, can be signs of very severe mental health disorders and are the most common reason for psychiatric admission (50%-60%).
While behavioral dysregulation is undeniably a huge problem for families, there has been an unreasonable 40-fold rise in diagnosis of bipolar disorder from 1994 to 2003, and 48% were prescribed atypical neuroleptics – medications with serious side effects. In response to this overdiagnosis as bipolar disorder, in 2013 the DSM-5 created a new diagnosis called disruptive mood dysregulation disorder (DMDD) to differentiate children who experience explosive outbursts who have a different outcome. This new classification includes children aged 6-12 years with persistent irritability most of the time, nearly every day, lasting at least 12 months and starting before age 10 years. DMDD diagnosis is not used after age 18 years.
To be diagnosed, the child has to have frequent, severe temper outbursts “grossly out of proportion” to the situation, averaging at least three times per week. The outbursts can be verbal or physical aggression to people, things, or themselves. While tantrums can be severe in children with delayed development, for the DMDD diagnosis these behaviors must be inconsistent with developmental level and must occur in at least two settings, and in one setting it must be severe. While outbursts are common, only half of children in one study of severe tantrum behavior in 5- to 9-year-olds also had the required persistent irritability.
If this does sound a lot like bipolar disorder so far, you are right. So what is different? DMDD has a prevalence of 2%-5% and occurs mostly in boys, whereas bipolar disorder affects boys and girls equally and affects less than 1% prior to adolescence.
The key features distinguishing DMDD from bipolar disorder are lack of an episodic nature to the irritability and lack of mania. Irritability in DMDD has to be persistently present with breaks of no more than 3 consecutive months in the defining 12-month period. There also cannot be any more than 1 day of the elevated mood features of mania or hypomania. Identifying mania is the hardest part, even in diagnosing adult bipolar, where it occurs only 1% of the year, much less in children who are generally lively! Hypomania, while less intense than mania, is when the person is energetic, talkative, and confident to an extreme extent, often with a flight of creative ideas. Excitement over birthdays or Christmas specifically does not count! So getting this history has to be done carefully, generally by a mental health professional, to make the distinction.
Interestingly, DMDD is not diagnosed when outbursts and irritability are better explained by autism spectrum disorder, separation anxiety disorder, or PTSD. To me, these exclusions point out the importance of sorting out the “set conditions” for all problematic behaviors, not always an easy task. Symptoms of autism in high functioning individuals can be quite subtle. Was the upset from change in a rigid routine known only to the child? Were sensory stimuli such as loud noises intolerable to this child? Was a nonverbal signal of a peer mistaken as a threat? While violent outbursts precipitated by these factors would still be considered “grossly out of proportion to the situation” for a typical child, they are not uncommon in atypical children. Similarly, children with separation anxiety disorder experience a high level of threat from even thinking about being apart from their caregivers, setting them up for alarm by situations other children would not find difficult.
The American Academy of Pediatrics emphasizes the need to assess all children for a history of psychological trauma. Traumas are quite common, and their sequelae affect many aspects of the child’s life; in the case of outbursts, it is emotional resilience that is impaired. As for all DSM-5 diagnoses, DMDD is not diagnosed when the irritability is due to physiological effects of a substance (e.g. steroids) or another medical or neurological disorder. Children with chronic pain conditions such as rheumatoid arthritis or sickle cell usually cope remarkably well, but when they don’t, their irritability should not be considered a mental health disorder. More commonly, sleep debt can produce chronic irritability and always should be assessed.
When coaching families about outbursts, I work to help them recognize that the child is not just angry, but very distressed. While “typical” tantrums last 1-5 minutes and show a rise then decline in intensity of the anger and distress, anger outbursts are longer and have an initial short and rapid burst of anger that then declines over the duration of the outburst, and with a steady but lower level of distress throughout.
The option to hug and verbally console the child’s distress is sometimes effective and does not reinforce the behavior unless the parent also yields to demands. But once outbursts begin, I liken them to a bomb going off – there is no intervention possible then. Instead, the task of the family, and over time that of the child, is to recognize and better manage the triggers.
Dr. Ross Greene, in his book, “The Explosive Child: A New Approach for Understanding and Parenting Easily Frustrated, Chronically Inflexible Children,” asserts that the child’s anger and distress can be interpreted as frustration from a gap in skills. This has treatment implications for identifying, educating about, and ameliorating the child’s weaknesses (deficits in understanding, communication, emotion regulation, flexibility or performance; or excess jealousy or hypersensitivity), and coaching parents to recognize, acknowledge, and avoid stressing these areas, if possible. I coach families to give points to the child for progressive little steps toward being able to recognize, verbalize, and inhibit outbursts with a reward system for the points. This helps put the parents and child “on the same team” in working on improving these skills.
Research on children with DMDD indicates that they show less positive affect when winning a “fixed” video game and are less able to suppress negative affect when losing. (Don’t forget to examine the role of real video games as precipitants of tantrums and contingently remove them!) Threshold for upset is lower and the degree of the upsets less well handled by children with DMDD.
In another study, when presented with a series of ambiguous facial expressions, children with DMDD were more likely to see anger in the faces than were controls. One hopeful result was that they could be taught to shift their perceptions significantly away from seeing anger, also reducing irritability and resulting in functional MRI changes. Such hostile bias attribution (tending to see threat) is well known to predispose to aggression. Cognitive behavioral therapy, the most effective counseling intervention, similarly teaches children to rethink their own negative thoughts before acting.
If irritability and rages were not enough, most children with DMDD have other psychiatric disorders; 39% having two, and 51% three or more (J Child Adolesc Psychopharmacol. 2013 Nov;23[9]:588-96). If not for the DMDD diagnosis, 82% would meet criteria for oppositional defiant disorder (ODD). The other common comorbidities are attention-deficit/hyperactivity disorder (ADHD) (74.5%), anxiety disorders (49.0%), and depression that is not major depressive disorder (MDD)(33.3%). When MDD is present, that diagnosis takes precedence. One cannot diagnose ODD, intermittent explosive disorder, or bipolar disorder along with DMDD, conditions from which it is intended to differentiate. Each of these comorbid disorders can be difficult to manage alone much less in combination, making DMDD a disorder deserving diagnosis and treatment by a mental health professional.
One of the main reasons DMDD was created is that children with these features go on to depressive or anxiety disorder in adolescence, not bipolar disorder.
While there is no treatment specific to DMDD, the depression component and prognosis suggest use of SSRIs, in addition to psychosocial therapies, and stimulants for the comorbid ADHD. Unfortunately, these two classes of medication are relatively contraindicated in bipolar disorder because they can lead to treatment-induced episodic mania (TEM). TEM occurs twice as often with antidepressants compared with stimulants (44% vs. 18%) in children with bipolar disorder (J Affect Disord. 2004 Oct 1;82[1]:149-58). Getting the diagnosis correct is, therefore, of great importance when medication is considered.
Approaches such as behavior modification, family therapy, and inpatient treatment can be effective for chronic irritability and aggression. Stimulant treatment of comorbid ADHD can decrease aggression and irritability. Alpha agonists such as guanfacine or clonidine also can help. In cases of partial improvement, adding either risperidone or divalproex may further decrease aggression in ADHD. In refractory aggression, risperidone has the best evidence. The Affective Reactivity Index or Outburst Monitoring Scale can be helpful in assessing severity and monitoring outcomes.
While a prognosis for depression rather than bipolar disorder sounds like a plus, in a longitudinal study, adults who had DMDD as children had worse outcomes, including being more likely to have adverse health outcomes (smoking, sexually transmitted infection), police contact, and low educational attainment, and being more likely to live in poverty, compared with controls who had other psychiatric disorders. While DMDD is a new and different diagnosis, it is similar to bipolar in having a potential course of life disruption, dangerous behaviors, suicide risk, and hospitalization.
Dr. Howard is assistant professor of pediatrics at the Johns Hopkins University, Baltimore, and creator of CHADIS (www.CHADIS.com). She had no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to Frontline. E-mail her at pdnews@frontlinemedcom.com.
The Starbucks generation
Iced, Half-Caff, Ristretto, Venti, 4-Pump, Sugar Free, Cinnamon, Dolce Soy Skinny Latte. Or Non-Fat Frappuccino with Extra Whipped Cream and Chocolate Sauce. Sorry, let me simplify: Triple, Venti, Soy, No Foam Latte. If you’re thinking I am speaking a foreign language, just ask a teen and they likely will be able to translate for you. This is normal Starbucks lingo. If you’re not a coffee drinker, you’re likely completely lost, but for those of us who live by the bean, it’s the language of love, caffeine love.
Twenty years ago, the thought of a teen drinking coffee was unheard of. Sure, soda has been there for decades, and in many cultures tea is a common drink, but today many kids are lining up at Starbucks for the caffeine jolt, and the new drinks such as 5-Hour Energy, Jolt, and Red Bull are making this generation the most sleep-deprived ever.
But how bad is caffeine for teens? The average adult consumes approximately 300 mg of caffeine per day,1 which is equivalent to 2-4 cups of coffee; this is considered to be a moderate intake. But the average teen intake of caffeine is not limited to just coffee. Many are consuming their favorite drink from Starbucks, then a few cans of soda, chocolate candy, and maybe even an energy drink – all before the school day is over. When we consider the content of caffeine in these products, the intake of caffeine is staggering.
For example, the average soda contains 35-55 mg of caffeine. Energy drinks such as Red Bull, Amp, and Monster contain approximately 150 mg of caffeine. A tall (small) Starbucks coffee also contains about 150 mg of caffeine, and when we increase the size to a grande, then we are looking at 320 mg.2,4 Simple math will show that the average teen likely has excessive intake of caffeine, resulting in adverse health effects.
The most concerning adverse effect is sleep deprivation.5 Physiologically, the circadian rhythm of adolescents changes and decreases the secretion of melatonin naturally, making it more difficult for them to fall asleep. With the addition of caffeine in high amounts, this is making falling asleep a greater challenge. Sleep deprivation leads to daytime sleepiness and inattention, resulting in learning issues.
Other ill effects found in some studies is that consumption of more than 220 mg of caffeine per day is associated with increased impulsivity, sensation seeking, and risk-taking behaviors.2 In people who are predisposed to arrhythmias, excessive intake can result in the onset of arrhythmias. Nervousness and jitteriness are other common effects.
Another consideration beyond the direct effects of caffeine is that it is usually coupled with sugary substances like those found in syrups used in Starbucks drinks, chocolate candy, and energy drinks. This has led to concerns of obesity as well as dental decay.
Now, when caffeine is taken in small to moderate amounts, less than 300 mg, there are health benefits. It certainly does improve concentration by attaching to the adenosine receptors that block the adenosine effect of sedation on the brain. This leads to improved concentration, memory retention, auditory vigilance, and reaction time.
Recent studies have shown that caffeine in moderate amounts can protect against Alzheimer’s, and is linked to a small decreased risk of cancer and liver disease. Coffee drinkers have also shown a moderate decrease in Parkinson’s disease and stroke.3,6
Regardless of the benefits of caffeine, the American Academy of Pediatrics has been very clear that it does not recommend caffeine in children. In its 2011 guideline,7 the extra calories, the risk of impulsive behavior, and sleep deprivation far outweighed any benefit that caffeine would have. It is critical that physicians educate their patients about foods that contain caffeine and the cumulative effect these foods have on their well-being, now and in the future.
References
1. “Trends in Caffeine Intake Among US Children and Adolescents” (Pediatrics 2014;133:386-93).
2. Caffeine Consumption Among Children and Adolescents. National Council on Strength and Fitness.
3. What is it about coffee? Harvard Health Letter (www.health.harvard.edu/staying-healthy/what-is-it-about-coffee).
4. Caffeine counts. American Physiological Association (Monitor on Psychology. 2001 June;32[6]).
5. J Pediatrics. 2011 March;158(3):508-9.
6. J Alzheimers Dis. 2010;20(suppl 1):s167-74.
7. Pediatrics 2011 June;127(6):1182-9
Dr. Pearce is a pediatrician in Frankfort, Ill.
Iced, Half-Caff, Ristretto, Venti, 4-Pump, Sugar Free, Cinnamon, Dolce Soy Skinny Latte. Or Non-Fat Frappuccino with Extra Whipped Cream and Chocolate Sauce. Sorry, let me simplify: Triple, Venti, Soy, No Foam Latte. If you’re thinking I am speaking a foreign language, just ask a teen and they likely will be able to translate for you. This is normal Starbucks lingo. If you’re not a coffee drinker, you’re likely completely lost, but for those of us who live by the bean, it’s the language of love, caffeine love.
Twenty years ago, the thought of a teen drinking coffee was unheard of. Sure, soda has been there for decades, and in many cultures tea is a common drink, but today many kids are lining up at Starbucks for the caffeine jolt, and the new drinks such as 5-Hour Energy, Jolt, and Red Bull are making this generation the most sleep-deprived ever.
But how bad is caffeine for teens? The average adult consumes approximately 300 mg of caffeine per day,1 which is equivalent to 2-4 cups of coffee; this is considered to be a moderate intake. But the average teen intake of caffeine is not limited to just coffee. Many are consuming their favorite drink from Starbucks, then a few cans of soda, chocolate candy, and maybe even an energy drink – all before the school day is over. When we consider the content of caffeine in these products, the intake of caffeine is staggering.
For example, the average soda contains 35-55 mg of caffeine. Energy drinks such as Red Bull, Amp, and Monster contain approximately 150 mg of caffeine. A tall (small) Starbucks coffee also contains about 150 mg of caffeine, and when we increase the size to a grande, then we are looking at 320 mg.2,4 Simple math will show that the average teen likely has excessive intake of caffeine, resulting in adverse health effects.
The most concerning adverse effect is sleep deprivation.5 Physiologically, the circadian rhythm of adolescents changes and decreases the secretion of melatonin naturally, making it more difficult for them to fall asleep. With the addition of caffeine in high amounts, this is making falling asleep a greater challenge. Sleep deprivation leads to daytime sleepiness and inattention, resulting in learning issues.
Other ill effects found in some studies is that consumption of more than 220 mg of caffeine per day is associated with increased impulsivity, sensation seeking, and risk-taking behaviors.2 In people who are predisposed to arrhythmias, excessive intake can result in the onset of arrhythmias. Nervousness and jitteriness are other common effects.
Another consideration beyond the direct effects of caffeine is that it is usually coupled with sugary substances like those found in syrups used in Starbucks drinks, chocolate candy, and energy drinks. This has led to concerns of obesity as well as dental decay.
Now, when caffeine is taken in small to moderate amounts, less than 300 mg, there are health benefits. It certainly does improve concentration by attaching to the adenosine receptors that block the adenosine effect of sedation on the brain. This leads to improved concentration, memory retention, auditory vigilance, and reaction time.
Recent studies have shown that caffeine in moderate amounts can protect against Alzheimer’s, and is linked to a small decreased risk of cancer and liver disease. Coffee drinkers have also shown a moderate decrease in Parkinson’s disease and stroke.3,6
Regardless of the benefits of caffeine, the American Academy of Pediatrics has been very clear that it does not recommend caffeine in children. In its 2011 guideline,7 the extra calories, the risk of impulsive behavior, and sleep deprivation far outweighed any benefit that caffeine would have. It is critical that physicians educate their patients about foods that contain caffeine and the cumulative effect these foods have on their well-being, now and in the future.
References
1. “Trends in Caffeine Intake Among US Children and Adolescents” (Pediatrics 2014;133:386-93).
2. Caffeine Consumption Among Children and Adolescents. National Council on Strength and Fitness.
3. What is it about coffee? Harvard Health Letter (www.health.harvard.edu/staying-healthy/what-is-it-about-coffee).
4. Caffeine counts. American Physiological Association (Monitor on Psychology. 2001 June;32[6]).
5. J Pediatrics. 2011 March;158(3):508-9.
6. J Alzheimers Dis. 2010;20(suppl 1):s167-74.
7. Pediatrics 2011 June;127(6):1182-9
Dr. Pearce is a pediatrician in Frankfort, Ill.
Iced, Half-Caff, Ristretto, Venti, 4-Pump, Sugar Free, Cinnamon, Dolce Soy Skinny Latte. Or Non-Fat Frappuccino with Extra Whipped Cream and Chocolate Sauce. Sorry, let me simplify: Triple, Venti, Soy, No Foam Latte. If you’re thinking I am speaking a foreign language, just ask a teen and they likely will be able to translate for you. This is normal Starbucks lingo. If you’re not a coffee drinker, you’re likely completely lost, but for those of us who live by the bean, it’s the language of love, caffeine love.
Twenty years ago, the thought of a teen drinking coffee was unheard of. Sure, soda has been there for decades, and in many cultures tea is a common drink, but today many kids are lining up at Starbucks for the caffeine jolt, and the new drinks such as 5-Hour Energy, Jolt, and Red Bull are making this generation the most sleep-deprived ever.
But how bad is caffeine for teens? The average adult consumes approximately 300 mg of caffeine per day,1 which is equivalent to 2-4 cups of coffee; this is considered to be a moderate intake. But the average teen intake of caffeine is not limited to just coffee. Many are consuming their favorite drink from Starbucks, then a few cans of soda, chocolate candy, and maybe even an energy drink – all before the school day is over. When we consider the content of caffeine in these products, the intake of caffeine is staggering.
For example, the average soda contains 35-55 mg of caffeine. Energy drinks such as Red Bull, Amp, and Monster contain approximately 150 mg of caffeine. A tall (small) Starbucks coffee also contains about 150 mg of caffeine, and when we increase the size to a grande, then we are looking at 320 mg.2,4 Simple math will show that the average teen likely has excessive intake of caffeine, resulting in adverse health effects.
The most concerning adverse effect is sleep deprivation.5 Physiologically, the circadian rhythm of adolescents changes and decreases the secretion of melatonin naturally, making it more difficult for them to fall asleep. With the addition of caffeine in high amounts, this is making falling asleep a greater challenge. Sleep deprivation leads to daytime sleepiness and inattention, resulting in learning issues.
Other ill effects found in some studies is that consumption of more than 220 mg of caffeine per day is associated with increased impulsivity, sensation seeking, and risk-taking behaviors.2 In people who are predisposed to arrhythmias, excessive intake can result in the onset of arrhythmias. Nervousness and jitteriness are other common effects.
Another consideration beyond the direct effects of caffeine is that it is usually coupled with sugary substances like those found in syrups used in Starbucks drinks, chocolate candy, and energy drinks. This has led to concerns of obesity as well as dental decay.
Now, when caffeine is taken in small to moderate amounts, less than 300 mg, there are health benefits. It certainly does improve concentration by attaching to the adenosine receptors that block the adenosine effect of sedation on the brain. This leads to improved concentration, memory retention, auditory vigilance, and reaction time.
Recent studies have shown that caffeine in moderate amounts can protect against Alzheimer’s, and is linked to a small decreased risk of cancer and liver disease. Coffee drinkers have also shown a moderate decrease in Parkinson’s disease and stroke.3,6
Regardless of the benefits of caffeine, the American Academy of Pediatrics has been very clear that it does not recommend caffeine in children. In its 2011 guideline,7 the extra calories, the risk of impulsive behavior, and sleep deprivation far outweighed any benefit that caffeine would have. It is critical that physicians educate their patients about foods that contain caffeine and the cumulative effect these foods have on their well-being, now and in the future.
References
1. “Trends in Caffeine Intake Among US Children and Adolescents” (Pediatrics 2014;133:386-93).
2. Caffeine Consumption Among Children and Adolescents. National Council on Strength and Fitness.
3. What is it about coffee? Harvard Health Letter (www.health.harvard.edu/staying-healthy/what-is-it-about-coffee).
4. Caffeine counts. American Physiological Association (Monitor on Psychology. 2001 June;32[6]).
5. J Pediatrics. 2011 March;158(3):508-9.
6. J Alzheimers Dis. 2010;20(suppl 1):s167-74.
7. Pediatrics 2011 June;127(6):1182-9
Dr. Pearce is a pediatrician in Frankfort, Ill.
Behavior problems in youth: Are things worse today than in the past?
Every generation of adults seems to worry that the next generation of youth is in trouble. The perception of kids today is no different, with theories abounding as to why the mental health of the newest generation is slipping, compared with previous standards. From mobile phones to helicopter parents, it might seem like a foregone conclusion that our current crop of young people is destined to be insecure, inattentive, and unable to cope with challenges and stress. Many news headlines on the latest mass shooting or standardized test results often seem to confirm these widespread concerns.
Pediatricians often hear parents lamenting the “good old days” when such things as corporal punishment were more easily accepted to help keep kids in line. But taking a step back, it may be worth a more objective look to examine the assumption that child behavioral problems are worse than ever. Measuring overall mental health is not an easy task, but looking at several important metrics indicate that things may not be nearly as bad as many people think.
Substance use
From the latest data from the Monitoring the Future Study, one of the nation’s most reliable sources on teen substance use, the use of both alcohol and tobacco among youth is at the lowest level since the study began in 1975. Use of drugs like heroin and ecstasy also are declining. The only major exception to this trend seems to be cannabis use, which has generally shown stable rates during this climate of marijuana decriminalization and, for some states, legalization.
Teen pregnancy rates
One area where there continues to be sustained progress is in teen pregnancy. According to the government’s Centers for Disease Control and Prevention, the overall pregnancy rate among adolescent females has been cut in half from 1991 to 2011, across many different ethnic groups. The rate fell from 61.8/1,000 teenagers aged 15-19 years to 31.3/1,000 teenagers.
Delinquency
Far fewer adolescents are being held against their will in juvenile detention centers. The number of youth who are incarcerated have dropped from a high of 381/100,000 in 1995 to 225/100,000 in 2010, according to a report by the Annie E. Casey Foundation.
Bullying
Bullying has been increasingly recognized as the public health problem that it is. The use of online technology also has created many new settings in which bullying can take place. Nevertheless, there is reason to be optimistic. From the National Center for Education Statistics and the National Crime Victimization Survey, the number of students who report being bullied at school has dropped from 32% in 2007 to an all-time low of 22% in 2013. Another recent study reached similar conclusions for bullying and many other forms of child victimization between 2003 and 2011 (JAMA Pediatr. 2014 Jun;168[6]:540-6).
Suicide
According to the CDC, the rate of completed suicide in youth peaked in the early1990s and then dropped and stabilized before starting to creep up again over the past 5 or so years. The trends are somewhat different, based on gender and the specific age group that is examined. The majority of completed youth suicides occur in males, with current rates still well below those historical highs.
Psychiatric disorders
This one is particularly tricky. While the rates of many specific psychiatric disorders such as ADHD and bipolar disorder have been rising in youth, as well as the use of psychiatric medications, it is much less clear whether this represents a true rise in these disorders versus other factors such as improved detection and a lower diagnostic threshold. One study by Achenbach et al. that measured quantitative levels of child behavior problems from the same rating scale over a 23-year time span found some increases in overall levels from the 1970s to the early 1990s, but then levels began to fall by the end of the millennium (J Abnorm Child Psychol. 2003 Feb;31[1]:1-11).
Of course, these hopeful trends in many significant areas do not mean that these problems have been overcome. While much work remains to be done on many fronts, it is still worth keeping in mind that the overall condition of youth mental health may not be as dire as we might be led to believe and that there is evidence that our efforts, perhaps, are leading to some progress.
Dr. Rettew is associate professor of psychiatry and pediatrics at the University of Vermont, Burlington. He said he has no relevant financial disclosures. Follow him on Twitter @pedipsych. E-mail him at pdnews@frontlinemedcom.com.
Every generation of adults seems to worry that the next generation of youth is in trouble. The perception of kids today is no different, with theories abounding as to why the mental health of the newest generation is slipping, compared with previous standards. From mobile phones to helicopter parents, it might seem like a foregone conclusion that our current crop of young people is destined to be insecure, inattentive, and unable to cope with challenges and stress. Many news headlines on the latest mass shooting or standardized test results often seem to confirm these widespread concerns.
Pediatricians often hear parents lamenting the “good old days” when such things as corporal punishment were more easily accepted to help keep kids in line. But taking a step back, it may be worth a more objective look to examine the assumption that child behavioral problems are worse than ever. Measuring overall mental health is not an easy task, but looking at several important metrics indicate that things may not be nearly as bad as many people think.
Substance use
From the latest data from the Monitoring the Future Study, one of the nation’s most reliable sources on teen substance use, the use of both alcohol and tobacco among youth is at the lowest level since the study began in 1975. Use of drugs like heroin and ecstasy also are declining. The only major exception to this trend seems to be cannabis use, which has generally shown stable rates during this climate of marijuana decriminalization and, for some states, legalization.
Teen pregnancy rates
One area where there continues to be sustained progress is in teen pregnancy. According to the government’s Centers for Disease Control and Prevention, the overall pregnancy rate among adolescent females has been cut in half from 1991 to 2011, across many different ethnic groups. The rate fell from 61.8/1,000 teenagers aged 15-19 years to 31.3/1,000 teenagers.
Delinquency
Far fewer adolescents are being held against their will in juvenile detention centers. The number of youth who are incarcerated have dropped from a high of 381/100,000 in 1995 to 225/100,000 in 2010, according to a report by the Annie E. Casey Foundation.
Bullying
Bullying has been increasingly recognized as the public health problem that it is. The use of online technology also has created many new settings in which bullying can take place. Nevertheless, there is reason to be optimistic. From the National Center for Education Statistics and the National Crime Victimization Survey, the number of students who report being bullied at school has dropped from 32% in 2007 to an all-time low of 22% in 2013. Another recent study reached similar conclusions for bullying and many other forms of child victimization between 2003 and 2011 (JAMA Pediatr. 2014 Jun;168[6]:540-6).
Suicide
According to the CDC, the rate of completed suicide in youth peaked in the early1990s and then dropped and stabilized before starting to creep up again over the past 5 or so years. The trends are somewhat different, based on gender and the specific age group that is examined. The majority of completed youth suicides occur in males, with current rates still well below those historical highs.
Psychiatric disorders
This one is particularly tricky. While the rates of many specific psychiatric disorders such as ADHD and bipolar disorder have been rising in youth, as well as the use of psychiatric medications, it is much less clear whether this represents a true rise in these disorders versus other factors such as improved detection and a lower diagnostic threshold. One study by Achenbach et al. that measured quantitative levels of child behavior problems from the same rating scale over a 23-year time span found some increases in overall levels from the 1970s to the early 1990s, but then levels began to fall by the end of the millennium (J Abnorm Child Psychol. 2003 Feb;31[1]:1-11).
Of course, these hopeful trends in many significant areas do not mean that these problems have been overcome. While much work remains to be done on many fronts, it is still worth keeping in mind that the overall condition of youth mental health may not be as dire as we might be led to believe and that there is evidence that our efforts, perhaps, are leading to some progress.
Dr. Rettew is associate professor of psychiatry and pediatrics at the University of Vermont, Burlington. He said he has no relevant financial disclosures. Follow him on Twitter @pedipsych. E-mail him at pdnews@frontlinemedcom.com.
Every generation of adults seems to worry that the next generation of youth is in trouble. The perception of kids today is no different, with theories abounding as to why the mental health of the newest generation is slipping, compared with previous standards. From mobile phones to helicopter parents, it might seem like a foregone conclusion that our current crop of young people is destined to be insecure, inattentive, and unable to cope with challenges and stress. Many news headlines on the latest mass shooting or standardized test results often seem to confirm these widespread concerns.
Pediatricians often hear parents lamenting the “good old days” when such things as corporal punishment were more easily accepted to help keep kids in line. But taking a step back, it may be worth a more objective look to examine the assumption that child behavioral problems are worse than ever. Measuring overall mental health is not an easy task, but looking at several important metrics indicate that things may not be nearly as bad as many people think.
Substance use
From the latest data from the Monitoring the Future Study, one of the nation’s most reliable sources on teen substance use, the use of both alcohol and tobacco among youth is at the lowest level since the study began in 1975. Use of drugs like heroin and ecstasy also are declining. The only major exception to this trend seems to be cannabis use, which has generally shown stable rates during this climate of marijuana decriminalization and, for some states, legalization.
Teen pregnancy rates
One area where there continues to be sustained progress is in teen pregnancy. According to the government’s Centers for Disease Control and Prevention, the overall pregnancy rate among adolescent females has been cut in half from 1991 to 2011, across many different ethnic groups. The rate fell from 61.8/1,000 teenagers aged 15-19 years to 31.3/1,000 teenagers.
Delinquency
Far fewer adolescents are being held against their will in juvenile detention centers. The number of youth who are incarcerated have dropped from a high of 381/100,000 in 1995 to 225/100,000 in 2010, according to a report by the Annie E. Casey Foundation.
Bullying
Bullying has been increasingly recognized as the public health problem that it is. The use of online technology also has created many new settings in which bullying can take place. Nevertheless, there is reason to be optimistic. From the National Center for Education Statistics and the National Crime Victimization Survey, the number of students who report being bullied at school has dropped from 32% in 2007 to an all-time low of 22% in 2013. Another recent study reached similar conclusions for bullying and many other forms of child victimization between 2003 and 2011 (JAMA Pediatr. 2014 Jun;168[6]:540-6).
Suicide
According to the CDC, the rate of completed suicide in youth peaked in the early1990s and then dropped and stabilized before starting to creep up again over the past 5 or so years. The trends are somewhat different, based on gender and the specific age group that is examined. The majority of completed youth suicides occur in males, with current rates still well below those historical highs.
Psychiatric disorders
This one is particularly tricky. While the rates of many specific psychiatric disorders such as ADHD and bipolar disorder have been rising in youth, as well as the use of psychiatric medications, it is much less clear whether this represents a true rise in these disorders versus other factors such as improved detection and a lower diagnostic threshold. One study by Achenbach et al. that measured quantitative levels of child behavior problems from the same rating scale over a 23-year time span found some increases in overall levels from the 1970s to the early 1990s, but then levels began to fall by the end of the millennium (J Abnorm Child Psychol. 2003 Feb;31[1]:1-11).
Of course, these hopeful trends in many significant areas do not mean that these problems have been overcome. While much work remains to be done on many fronts, it is still worth keeping in mind that the overall condition of youth mental health may not be as dire as we might be led to believe and that there is evidence that our efforts, perhaps, are leading to some progress.
Dr. Rettew is associate professor of psychiatry and pediatrics at the University of Vermont, Burlington. He said he has no relevant financial disclosures. Follow him on Twitter @pedipsych. E-mail him at pdnews@frontlinemedcom.com.
New Testing Guidelines for Infants With Possible Zika Virus Infection
The Centers for Disease Control and Prevention has released interim guidelines for U.S. clinicians caring for infants born to mothers who traveled to or resided in an area with Zika virus transmission during pregnancy.
The guidelines, released Jan. 26, address the evaluation and testing of infants with possible congenital Zika virus infection, and follow the Jan. 19 release of similar guidelines for the care of pregnant women with possible exposure to the mosquito-borne virus. Most importantly, the new guidelines say Zika virus testing should be performed for infants with microcephaly or intracranial calcifications who are born to women with possible Zika virus exposure during pregnancy, and for infants born to women with positive or inconclusive Zika virus test results.
“Pediatric health are providers should work closely with obstetric providers to identify infants whose mothers were potentially infected with Zika virus during pregnancy (based on travel to or residence in an area with Zika virus transmission),” according to the guidelines, which were published in Morbidity and Mortality Weekly Report (MMWR. 2016 Jan 26;65[Early Release:1-5]).
Infants with laboratory evidence of a possible congenital Zika virus infection should undergo additional clinical evaluation, and state or territorial health departments should be contacted to facilitate testing. Zika virus disease is an arboviral disease and thus is a nationally notifiable condition, according to guideline authors Dr. J. Erin Staples and her colleagues at the CDC, Atlanta.
Both molecular and serologic tests are recommended for infants undergoing evaluation for possible congenital Zika virus infection, they noted.
Serum specimens for reverse-transcription-polymerase chain reaction testing should be collected from the umbilical cord or directly from the infant within 2 days of birth, and cerebrospinal fluid collected for other studies, as well as frozen and fixed placenta obtained at delivery, should also be tested by RT-PCR.
IgM ELISA for Zika virus and dengue virus should also be performed on infant serum, infant CSF, and maternal serum, but results from these assays can be falsely positive because of cross-reacting antibodies, the authors noted.
Other tests that can be considered include a plaque reduction neutralization test to measure virus-specific neutralizing antibodies and to discriminate between cross-reacting antibodies and closely related flaviviruses, and immunohistochemical staining to detect the virus antigen on fixed placenta and umbilical cord tissues.
Further clinical evaluation and laboratory testing is recommended for infants with microcephaly or intracranial calcifications detected prenatally or at birth if the mother was potentially infected during pregnancy, they said.
In infants with possible Zika virus exposure during pregnancy, but without microcephaly or intracranial calcification, subsequent evaluation depends on maternal testing results. Routine care is recommended if maternal test results are negative, and testing for a possible congenital infection is recommended if maternal results are positive or inconclusive.
If all of an infant’s tests are negative for Zika virus infection, no further Zika virus testing or evaluation is recommended. In the event of any positive or inconclusive test, further evaluation and follow-up is recommended.
Other considerations
Abnormal eye findings have been reported in infants with possible congenital infection, therefore an opthalmologic evaluation, including retinal examination is advised during the first month of life, as is a repeat hearing screen at age 6 months – even if the initial screen was normal, the authors said.
The infant should be followed to assess for long-term sequelae, and the case should be reported. Follow-up should include a cranial ultrasound to assess for subclinical findings, unless a third trimester ultrasound showed no brain abnormalities, they added.
No specific antiviral treatment or vaccine exists for Zika virus infection; treatment is supportive and should address specific medical and neurodevelopmental issues, and mothers should be encouraged to breastfeed infants regardless of exposure, as available evidence suggests the benefits of breastfeeding outweigh the theoretical risks of transmission through breast milk, they said.
The authors stressed that prevention of maternal infection is the only way to prevent congenital Zika virus infection and is achieved by avoiding areas with ongoing Zika virus transmission or by strictly following steps to avoid mosquito bites by using air-conditioning or window and door screens, wearing protective clothing, and using insect repellents.
Environmental Protection Agency–registered insect repellents are safe for pregnant women when used according to the product label, they noted.
The Centers for Disease Control and Prevention has released interim guidelines for U.S. clinicians caring for infants born to mothers who traveled to or resided in an area with Zika virus transmission during pregnancy.
The guidelines, released Jan. 26, address the evaluation and testing of infants with possible congenital Zika virus infection, and follow the Jan. 19 release of similar guidelines for the care of pregnant women with possible exposure to the mosquito-borne virus. Most importantly, the new guidelines say Zika virus testing should be performed for infants with microcephaly or intracranial calcifications who are born to women with possible Zika virus exposure during pregnancy, and for infants born to women with positive or inconclusive Zika virus test results.
“Pediatric health are providers should work closely with obstetric providers to identify infants whose mothers were potentially infected with Zika virus during pregnancy (based on travel to or residence in an area with Zika virus transmission),” according to the guidelines, which were published in Morbidity and Mortality Weekly Report (MMWR. 2016 Jan 26;65[Early Release:1-5]).
Infants with laboratory evidence of a possible congenital Zika virus infection should undergo additional clinical evaluation, and state or territorial health departments should be contacted to facilitate testing. Zika virus disease is an arboviral disease and thus is a nationally notifiable condition, according to guideline authors Dr. J. Erin Staples and her colleagues at the CDC, Atlanta.
Both molecular and serologic tests are recommended for infants undergoing evaluation for possible congenital Zika virus infection, they noted.
Serum specimens for reverse-transcription-polymerase chain reaction testing should be collected from the umbilical cord or directly from the infant within 2 days of birth, and cerebrospinal fluid collected for other studies, as well as frozen and fixed placenta obtained at delivery, should also be tested by RT-PCR.
IgM ELISA for Zika virus and dengue virus should also be performed on infant serum, infant CSF, and maternal serum, but results from these assays can be falsely positive because of cross-reacting antibodies, the authors noted.
Other tests that can be considered include a plaque reduction neutralization test to measure virus-specific neutralizing antibodies and to discriminate between cross-reacting antibodies and closely related flaviviruses, and immunohistochemical staining to detect the virus antigen on fixed placenta and umbilical cord tissues.
Further clinical evaluation and laboratory testing is recommended for infants with microcephaly or intracranial calcifications detected prenatally or at birth if the mother was potentially infected during pregnancy, they said.
In infants with possible Zika virus exposure during pregnancy, but without microcephaly or intracranial calcification, subsequent evaluation depends on maternal testing results. Routine care is recommended if maternal test results are negative, and testing for a possible congenital infection is recommended if maternal results are positive or inconclusive.
If all of an infant’s tests are negative for Zika virus infection, no further Zika virus testing or evaluation is recommended. In the event of any positive or inconclusive test, further evaluation and follow-up is recommended.
Other considerations
Abnormal eye findings have been reported in infants with possible congenital infection, therefore an opthalmologic evaluation, including retinal examination is advised during the first month of life, as is a repeat hearing screen at age 6 months – even if the initial screen was normal, the authors said.
The infant should be followed to assess for long-term sequelae, and the case should be reported. Follow-up should include a cranial ultrasound to assess for subclinical findings, unless a third trimester ultrasound showed no brain abnormalities, they added.
No specific antiviral treatment or vaccine exists for Zika virus infection; treatment is supportive and should address specific medical and neurodevelopmental issues, and mothers should be encouraged to breastfeed infants regardless of exposure, as available evidence suggests the benefits of breastfeeding outweigh the theoretical risks of transmission through breast milk, they said.
The authors stressed that prevention of maternal infection is the only way to prevent congenital Zika virus infection and is achieved by avoiding areas with ongoing Zika virus transmission or by strictly following steps to avoid mosquito bites by using air-conditioning or window and door screens, wearing protective clothing, and using insect repellents.
Environmental Protection Agency–registered insect repellents are safe for pregnant women when used according to the product label, they noted.
The Centers for Disease Control and Prevention has released interim guidelines for U.S. clinicians caring for infants born to mothers who traveled to or resided in an area with Zika virus transmission during pregnancy.
The guidelines, released Jan. 26, address the evaluation and testing of infants with possible congenital Zika virus infection, and follow the Jan. 19 release of similar guidelines for the care of pregnant women with possible exposure to the mosquito-borne virus. Most importantly, the new guidelines say Zika virus testing should be performed for infants with microcephaly or intracranial calcifications who are born to women with possible Zika virus exposure during pregnancy, and for infants born to women with positive or inconclusive Zika virus test results.
“Pediatric health are providers should work closely with obstetric providers to identify infants whose mothers were potentially infected with Zika virus during pregnancy (based on travel to or residence in an area with Zika virus transmission),” according to the guidelines, which were published in Morbidity and Mortality Weekly Report (MMWR. 2016 Jan 26;65[Early Release:1-5]).
Infants with laboratory evidence of a possible congenital Zika virus infection should undergo additional clinical evaluation, and state or territorial health departments should be contacted to facilitate testing. Zika virus disease is an arboviral disease and thus is a nationally notifiable condition, according to guideline authors Dr. J. Erin Staples and her colleagues at the CDC, Atlanta.
Both molecular and serologic tests are recommended for infants undergoing evaluation for possible congenital Zika virus infection, they noted.
Serum specimens for reverse-transcription-polymerase chain reaction testing should be collected from the umbilical cord or directly from the infant within 2 days of birth, and cerebrospinal fluid collected for other studies, as well as frozen and fixed placenta obtained at delivery, should also be tested by RT-PCR.
IgM ELISA for Zika virus and dengue virus should also be performed on infant serum, infant CSF, and maternal serum, but results from these assays can be falsely positive because of cross-reacting antibodies, the authors noted.
Other tests that can be considered include a plaque reduction neutralization test to measure virus-specific neutralizing antibodies and to discriminate between cross-reacting antibodies and closely related flaviviruses, and immunohistochemical staining to detect the virus antigen on fixed placenta and umbilical cord tissues.
Further clinical evaluation and laboratory testing is recommended for infants with microcephaly or intracranial calcifications detected prenatally or at birth if the mother was potentially infected during pregnancy, they said.
In infants with possible Zika virus exposure during pregnancy, but without microcephaly or intracranial calcification, subsequent evaluation depends on maternal testing results. Routine care is recommended if maternal test results are negative, and testing for a possible congenital infection is recommended if maternal results are positive or inconclusive.
If all of an infant’s tests are negative for Zika virus infection, no further Zika virus testing or evaluation is recommended. In the event of any positive or inconclusive test, further evaluation and follow-up is recommended.
Other considerations
Abnormal eye findings have been reported in infants with possible congenital infection, therefore an opthalmologic evaluation, including retinal examination is advised during the first month of life, as is a repeat hearing screen at age 6 months – even if the initial screen was normal, the authors said.
The infant should be followed to assess for long-term sequelae, and the case should be reported. Follow-up should include a cranial ultrasound to assess for subclinical findings, unless a third trimester ultrasound showed no brain abnormalities, they added.
No specific antiviral treatment or vaccine exists for Zika virus infection; treatment is supportive and should address specific medical and neurodevelopmental issues, and mothers should be encouraged to breastfeed infants regardless of exposure, as available evidence suggests the benefits of breastfeeding outweigh the theoretical risks of transmission through breast milk, they said.
The authors stressed that prevention of maternal infection is the only way to prevent congenital Zika virus infection and is achieved by avoiding areas with ongoing Zika virus transmission or by strictly following steps to avoid mosquito bites by using air-conditioning or window and door screens, wearing protective clothing, and using insect repellents.
Environmental Protection Agency–registered insect repellents are safe for pregnant women when used according to the product label, they noted.
FROM MMWR
New testing guidelines for infants with possible Zika virus infection
The Centers for Disease Control and Prevention has released interim guidelines for U.S. clinicians caring for infants born to mothers who traveled to or resided in an area with Zika virus transmission during pregnancy.
The guidelines, released Jan. 26, address the evaluation and testing of infants with possible congenital Zika virus infection, and follow the Jan. 19 release of similar guidelines for the care of pregnant women with possible exposure to the mosquito-borne virus. Most importantly, the new guidelines say Zika virus testing should be performed for infants with microcephaly or intracranial calcifications who are born to women with possible Zika virus exposure during pregnancy, and for infants born to women with positive or inconclusive Zika virus test results.
“Pediatric health are providers should work closely with obstetric providers to identify infants whose mothers were potentially infected with Zika virus during pregnancy (based on travel to or residence in an area with Zika virus transmission),” according to the guidelines, which were published in Morbidity and Mortality Weekly Report (MMWR. 2016 Jan 26;65[Early Release:1-5]).
Infants with laboratory evidence of a possible congenital Zika virus infection should undergo additional clinical evaluation, and state or territorial health departments should be contacted to facilitate testing. Zika virus disease is an arboviral disease and thus is a nationally notifiable condition, according to guideline authors Dr. J. Erin Staples and her colleagues at the CDC, Atlanta.
Both molecular and serologic tests are recommended for infants undergoing evaluation for possible congenital Zika virus infection, they noted.
Serum specimens for reverse-transcription-polymerase chain reaction testing should be collected from the umbilical cord or directly from the infant within 2 days of birth, and cerebrospinal fluid collected for other studies, as well as frozen and fixed placenta obtained at delivery, should also be tested by RT-PCR.
IgM ELISA for Zika virus and dengue virus should also be performed on infant serum, infant CSF, and maternal serum, but results from these assays can be falsely positive because of cross-reacting antibodies, the authors noted.
Other tests that can be considered include a plaque reduction neutralization test to measure virus-specific neutralizing antibodies and to discriminate between cross-reacting antibodies and closely related flaviviruses, and immunohistochemical staining to detect the virus antigen on fixed placenta and umbilical cord tissues.
Further clinical evaluation and laboratory testing is recommended for infants with microcephaly or intracranial calcifications detected prenatally or at birth if the mother was potentially infected during pregnancy, they said.
In infants with possible Zika virus exposure during pregnancy, but without microcephaly or intracranial calcification, subsequent evaluation depends on maternal testing results. Routine care is recommended if maternal test results are negative, and testing for a possible congenital infection is recommended if maternal results are positive or inconclusive.
If all of an infant’s tests are negative for Zika virus infection, no further Zika virus testing or evaluation is recommended. In the event of any positive or inconclusive test, further evaluation and follow-up is recommended.
Other considerations
Abnormal eye findings have been reported in infants with possible congenital infection, therefore an opthalmologic evaluation, including retinal examination is advised during the first month of life, as is a repeat hearing screen at age 6 months – even if the initial screen was normal, the authors said.
The infant should be followed to assess for long-term sequelae, and the case should be reported. Follow-up should include a cranial ultrasound to assess for subclinical findings, unless a third trimester ultrasound showed no brain abnormalities, they added.
No specific antiviral treatment or vaccine exists for Zika virus infection; treatment is supportive and should address specific medical and neurodevelopmental issues, and mothers should be encouraged to breastfeed infants regardless of exposure, as available evidence suggests the benefits of breastfeeding outweigh the theoretical risks of transmission through breast milk, they said.
The authors stressed that prevention of maternal infection is the only way to prevent congenital Zika virus infection and is achieved by avoiding areas with ongoing Zika virus transmission or by strictly following steps to avoid mosquito bites by using air-conditioning or window and door screens, wearing protective clothing, and using insect repellents.
Environmental Protection Agency–registered insect repellents are safe for pregnant women when used according to the product label, they noted.
The Centers for Disease Control and Prevention has released interim guidelines for U.S. clinicians caring for infants born to mothers who traveled to or resided in an area with Zika virus transmission during pregnancy.
The guidelines, released Jan. 26, address the evaluation and testing of infants with possible congenital Zika virus infection, and follow the Jan. 19 release of similar guidelines for the care of pregnant women with possible exposure to the mosquito-borne virus. Most importantly, the new guidelines say Zika virus testing should be performed for infants with microcephaly or intracranial calcifications who are born to women with possible Zika virus exposure during pregnancy, and for infants born to women with positive or inconclusive Zika virus test results.
“Pediatric health are providers should work closely with obstetric providers to identify infants whose mothers were potentially infected with Zika virus during pregnancy (based on travel to or residence in an area with Zika virus transmission),” according to the guidelines, which were published in Morbidity and Mortality Weekly Report (MMWR. 2016 Jan 26;65[Early Release:1-5]).
Infants with laboratory evidence of a possible congenital Zika virus infection should undergo additional clinical evaluation, and state or territorial health departments should be contacted to facilitate testing. Zika virus disease is an arboviral disease and thus is a nationally notifiable condition, according to guideline authors Dr. J. Erin Staples and her colleagues at the CDC, Atlanta.
Both molecular and serologic tests are recommended for infants undergoing evaluation for possible congenital Zika virus infection, they noted.
Serum specimens for reverse-transcription-polymerase chain reaction testing should be collected from the umbilical cord or directly from the infant within 2 days of birth, and cerebrospinal fluid collected for other studies, as well as frozen and fixed placenta obtained at delivery, should also be tested by RT-PCR.
IgM ELISA for Zika virus and dengue virus should also be performed on infant serum, infant CSF, and maternal serum, but results from these assays can be falsely positive because of cross-reacting antibodies, the authors noted.
Other tests that can be considered include a plaque reduction neutralization test to measure virus-specific neutralizing antibodies and to discriminate between cross-reacting antibodies and closely related flaviviruses, and immunohistochemical staining to detect the virus antigen on fixed placenta and umbilical cord tissues.
Further clinical evaluation and laboratory testing is recommended for infants with microcephaly or intracranial calcifications detected prenatally or at birth if the mother was potentially infected during pregnancy, they said.
In infants with possible Zika virus exposure during pregnancy, but without microcephaly or intracranial calcification, subsequent evaluation depends on maternal testing results. Routine care is recommended if maternal test results are negative, and testing for a possible congenital infection is recommended if maternal results are positive or inconclusive.
If all of an infant’s tests are negative for Zika virus infection, no further Zika virus testing or evaluation is recommended. In the event of any positive or inconclusive test, further evaluation and follow-up is recommended.
Other considerations
Abnormal eye findings have been reported in infants with possible congenital infection, therefore an opthalmologic evaluation, including retinal examination is advised during the first month of life, as is a repeat hearing screen at age 6 months – even if the initial screen was normal, the authors said.
The infant should be followed to assess for long-term sequelae, and the case should be reported. Follow-up should include a cranial ultrasound to assess for subclinical findings, unless a third trimester ultrasound showed no brain abnormalities, they added.
No specific antiviral treatment or vaccine exists for Zika virus infection; treatment is supportive and should address specific medical and neurodevelopmental issues, and mothers should be encouraged to breastfeed infants regardless of exposure, as available evidence suggests the benefits of breastfeeding outweigh the theoretical risks of transmission through breast milk, they said.
The authors stressed that prevention of maternal infection is the only way to prevent congenital Zika virus infection and is achieved by avoiding areas with ongoing Zika virus transmission or by strictly following steps to avoid mosquito bites by using air-conditioning or window and door screens, wearing protective clothing, and using insect repellents.
Environmental Protection Agency–registered insect repellents are safe for pregnant women when used according to the product label, they noted.
The Centers for Disease Control and Prevention has released interim guidelines for U.S. clinicians caring for infants born to mothers who traveled to or resided in an area with Zika virus transmission during pregnancy.
The guidelines, released Jan. 26, address the evaluation and testing of infants with possible congenital Zika virus infection, and follow the Jan. 19 release of similar guidelines for the care of pregnant women with possible exposure to the mosquito-borne virus. Most importantly, the new guidelines say Zika virus testing should be performed for infants with microcephaly or intracranial calcifications who are born to women with possible Zika virus exposure during pregnancy, and for infants born to women with positive or inconclusive Zika virus test results.
“Pediatric health are providers should work closely with obstetric providers to identify infants whose mothers were potentially infected with Zika virus during pregnancy (based on travel to or residence in an area with Zika virus transmission),” according to the guidelines, which were published in Morbidity and Mortality Weekly Report (MMWR. 2016 Jan 26;65[Early Release:1-5]).
Infants with laboratory evidence of a possible congenital Zika virus infection should undergo additional clinical evaluation, and state or territorial health departments should be contacted to facilitate testing. Zika virus disease is an arboviral disease and thus is a nationally notifiable condition, according to guideline authors Dr. J. Erin Staples and her colleagues at the CDC, Atlanta.
Both molecular and serologic tests are recommended for infants undergoing evaluation for possible congenital Zika virus infection, they noted.
Serum specimens for reverse-transcription-polymerase chain reaction testing should be collected from the umbilical cord or directly from the infant within 2 days of birth, and cerebrospinal fluid collected for other studies, as well as frozen and fixed placenta obtained at delivery, should also be tested by RT-PCR.
IgM ELISA for Zika virus and dengue virus should also be performed on infant serum, infant CSF, and maternal serum, but results from these assays can be falsely positive because of cross-reacting antibodies, the authors noted.
Other tests that can be considered include a plaque reduction neutralization test to measure virus-specific neutralizing antibodies and to discriminate between cross-reacting antibodies and closely related flaviviruses, and immunohistochemical staining to detect the virus antigen on fixed placenta and umbilical cord tissues.
Further clinical evaluation and laboratory testing is recommended for infants with microcephaly or intracranial calcifications detected prenatally or at birth if the mother was potentially infected during pregnancy, they said.
In infants with possible Zika virus exposure during pregnancy, but without microcephaly or intracranial calcification, subsequent evaluation depends on maternal testing results. Routine care is recommended if maternal test results are negative, and testing for a possible congenital infection is recommended if maternal results are positive or inconclusive.
If all of an infant’s tests are negative for Zika virus infection, no further Zika virus testing or evaluation is recommended. In the event of any positive or inconclusive test, further evaluation and follow-up is recommended.
Other considerations
Abnormal eye findings have been reported in infants with possible congenital infection, therefore an opthalmologic evaluation, including retinal examination is advised during the first month of life, as is a repeat hearing screen at age 6 months – even if the initial screen was normal, the authors said.
The infant should be followed to assess for long-term sequelae, and the case should be reported. Follow-up should include a cranial ultrasound to assess for subclinical findings, unless a third trimester ultrasound showed no brain abnormalities, they added.
No specific antiviral treatment or vaccine exists for Zika virus infection; treatment is supportive and should address specific medical and neurodevelopmental issues, and mothers should be encouraged to breastfeed infants regardless of exposure, as available evidence suggests the benefits of breastfeeding outweigh the theoretical risks of transmission through breast milk, they said.
The authors stressed that prevention of maternal infection is the only way to prevent congenital Zika virus infection and is achieved by avoiding areas with ongoing Zika virus transmission or by strictly following steps to avoid mosquito bites by using air-conditioning or window and door screens, wearing protective clothing, and using insect repellents.
Environmental Protection Agency–registered insect repellents are safe for pregnant women when used according to the product label, they noted.
FROM MMWR
Studies backed propranolol in treating infantile hemangioma
Two new studies underscore the important role of oral propranolol in the first-line treatment of infantile hemangioma (IH), as well as the need for better long-term data on the safety of the beta-blocker in very young children, according to the authors.
In the first study, an uncontrolled prospective analysis of 906 infants with IH, 84% of those who stopped propranolol did so because of “satisfactory efficacy” while only 6% discontinued because of adverse drug reactions (ADRs), reported Dr. Sorilla Prey at Bordeaux (France) University and her associates. The median dose of propranolol was 2 mg/kg per day for 198 days, with a median follow-up period of 396 days, in the study, which was published on Jan. 26, in a research letter (JAMA. 2016 Jan 26;315;413-5).
Almost 9% had ADRs; most involved respiratory infections. Serious ADRs affected 2.6% of patients; the most serious were cardiac and metabolic disorders. They included one episode of serious bradycardia, as well as one fatal episode of atrioventricular block considered probably unrelated to therapy.
In a separate meta-analysis of 18 studies published online in Pediatrics in January, treatment with propranolol cleared an average of 95% of IH cases, more than double the average clearance for corticosteroids (Pediatrics. 2016 Jan 15. pii: peds.2015-3896). Harms “were relatively well tolerated in the short term,” but needed longer-term study, especially of cardiovascular and metabolic effects and effects on cognition, memory, and the central nervous system, said the authors, Dr. Sivakumar Chinnadurai of Vanderbilt University, Nashville, Tenn., and his associates.
A linked comparative effectiveness review, based on this research and published by the Agency for Healthcare Research and Quality found a “moderate” strength of evidence for oral propranolol over steroids, alongside “moderate” evidence linking the beta-blocker to potential harms.
In an interview, Dr. Michael Cabana, who was not involved the studies, noted that historically, lesions were considered benign, but that management “has changed tremendously in the last few years.” Systematic reviews suggest that propranolol is “extremely effective” in treating IH, said Dr. Cabana, professor of pediatrics at the University of California, San Francisco. “But every child and every IH lesion is different. Usually, for thin, superficial IH lesions in low-risk areas, topical corticosteroids can still be useful.”
Because the early growth of IH is nonlinear and occurs fastest at about 1-2 months of age, high-risk patients should be referred to a pediatric dermatologist by age 4 weeks, Dr. Cabana said. These include patients with facial or ulcerated hemangiomas, lesions that could threaten vision or the airway, those associated with other anomalies, or lesions in the perineal area or lumbosacral area, he added. Propranolol can cause sleep disruption and cold hands and feet, he noted. Cardiovascular effects are “usually minor,” while hypoglycemia is usually the most serious ADR.
The overall rate of treatment-related hypoglycemia in the JAMA study was only 0.4%, but half these patients had hypoglycemic seizures. Hypoglycemia was “aggravated by the beta-adrenergic antagonist properties of propranolol, and worsening conditions of children who also had other concomitant diseases,” Dr. Prey and her associates said. Despite monitoring, bradycardia also occurred in patients with severe comorbidities.
“Prescribers must counsel parents at each follow-up visit to discontinue propranolol during fasting and intercurrent illness, especially in the setting of restricted oral intake and respiratory symptoms,” they emphasized.
The comparative effectiveness review included 148 studies and 15 randomized controlled trials. Few studies compared lasers and beta-blockers, but lasers historically have yielded much lower success rates than have more recent studies of propranolol, the researchers noted. Pulsed dye laser was generally more effective than were other laser modalities, with moderate strength of evidence for improvement in skin pigmentation and relatively low risk of pain.
A third study also published in January reported that infantile hemangiomas have become more common in recent decades in conjunction with declines in gestational age and birth weight (J Am Acad Dermatol. 2016 Jan;74 [1] 120-6).
Dr. Prey and her associates were funded by Pierre Fabre Dermatologie and the French Health Products Agency. She and one coinvestigator reported involvement in clinical trials of propranolol for infantile hemangioma. The other researchers had no disclosures. The systematic review was supported by the Agency for Healthcare Research and Quality, U.S. Department of Health & Human Services. The investigators had no disclosures.
Two new studies underscore the important role of oral propranolol in the first-line treatment of infantile hemangioma (IH), as well as the need for better long-term data on the safety of the beta-blocker in very young children, according to the authors.
In the first study, an uncontrolled prospective analysis of 906 infants with IH, 84% of those who stopped propranolol did so because of “satisfactory efficacy” while only 6% discontinued because of adverse drug reactions (ADRs), reported Dr. Sorilla Prey at Bordeaux (France) University and her associates. The median dose of propranolol was 2 mg/kg per day for 198 days, with a median follow-up period of 396 days, in the study, which was published on Jan. 26, in a research letter (JAMA. 2016 Jan 26;315;413-5).
Almost 9% had ADRs; most involved respiratory infections. Serious ADRs affected 2.6% of patients; the most serious were cardiac and metabolic disorders. They included one episode of serious bradycardia, as well as one fatal episode of atrioventricular block considered probably unrelated to therapy.
In a separate meta-analysis of 18 studies published online in Pediatrics in January, treatment with propranolol cleared an average of 95% of IH cases, more than double the average clearance for corticosteroids (Pediatrics. 2016 Jan 15. pii: peds.2015-3896). Harms “were relatively well tolerated in the short term,” but needed longer-term study, especially of cardiovascular and metabolic effects and effects on cognition, memory, and the central nervous system, said the authors, Dr. Sivakumar Chinnadurai of Vanderbilt University, Nashville, Tenn., and his associates.
A linked comparative effectiveness review, based on this research and published by the Agency for Healthcare Research and Quality found a “moderate” strength of evidence for oral propranolol over steroids, alongside “moderate” evidence linking the beta-blocker to potential harms.
In an interview, Dr. Michael Cabana, who was not involved the studies, noted that historically, lesions were considered benign, but that management “has changed tremendously in the last few years.” Systematic reviews suggest that propranolol is “extremely effective” in treating IH, said Dr. Cabana, professor of pediatrics at the University of California, San Francisco. “But every child and every IH lesion is different. Usually, for thin, superficial IH lesions in low-risk areas, topical corticosteroids can still be useful.”
Because the early growth of IH is nonlinear and occurs fastest at about 1-2 months of age, high-risk patients should be referred to a pediatric dermatologist by age 4 weeks, Dr. Cabana said. These include patients with facial or ulcerated hemangiomas, lesions that could threaten vision or the airway, those associated with other anomalies, or lesions in the perineal area or lumbosacral area, he added. Propranolol can cause sleep disruption and cold hands and feet, he noted. Cardiovascular effects are “usually minor,” while hypoglycemia is usually the most serious ADR.
The overall rate of treatment-related hypoglycemia in the JAMA study was only 0.4%, but half these patients had hypoglycemic seizures. Hypoglycemia was “aggravated by the beta-adrenergic antagonist properties of propranolol, and worsening conditions of children who also had other concomitant diseases,” Dr. Prey and her associates said. Despite monitoring, bradycardia also occurred in patients with severe comorbidities.
“Prescribers must counsel parents at each follow-up visit to discontinue propranolol during fasting and intercurrent illness, especially in the setting of restricted oral intake and respiratory symptoms,” they emphasized.
The comparative effectiveness review included 148 studies and 15 randomized controlled trials. Few studies compared lasers and beta-blockers, but lasers historically have yielded much lower success rates than have more recent studies of propranolol, the researchers noted. Pulsed dye laser was generally more effective than were other laser modalities, with moderate strength of evidence for improvement in skin pigmentation and relatively low risk of pain.
A third study also published in January reported that infantile hemangiomas have become more common in recent decades in conjunction with declines in gestational age and birth weight (J Am Acad Dermatol. 2016 Jan;74 [1] 120-6).
Dr. Prey and her associates were funded by Pierre Fabre Dermatologie and the French Health Products Agency. She and one coinvestigator reported involvement in clinical trials of propranolol for infantile hemangioma. The other researchers had no disclosures. The systematic review was supported by the Agency for Healthcare Research and Quality, U.S. Department of Health & Human Services. The investigators had no disclosures.
Two new studies underscore the important role of oral propranolol in the first-line treatment of infantile hemangioma (IH), as well as the need for better long-term data on the safety of the beta-blocker in very young children, according to the authors.
In the first study, an uncontrolled prospective analysis of 906 infants with IH, 84% of those who stopped propranolol did so because of “satisfactory efficacy” while only 6% discontinued because of adverse drug reactions (ADRs), reported Dr. Sorilla Prey at Bordeaux (France) University and her associates. The median dose of propranolol was 2 mg/kg per day for 198 days, with a median follow-up period of 396 days, in the study, which was published on Jan. 26, in a research letter (JAMA. 2016 Jan 26;315;413-5).
Almost 9% had ADRs; most involved respiratory infections. Serious ADRs affected 2.6% of patients; the most serious were cardiac and metabolic disorders. They included one episode of serious bradycardia, as well as one fatal episode of atrioventricular block considered probably unrelated to therapy.
In a separate meta-analysis of 18 studies published online in Pediatrics in January, treatment with propranolol cleared an average of 95% of IH cases, more than double the average clearance for corticosteroids (Pediatrics. 2016 Jan 15. pii: peds.2015-3896). Harms “were relatively well tolerated in the short term,” but needed longer-term study, especially of cardiovascular and metabolic effects and effects on cognition, memory, and the central nervous system, said the authors, Dr. Sivakumar Chinnadurai of Vanderbilt University, Nashville, Tenn., and his associates.
A linked comparative effectiveness review, based on this research and published by the Agency for Healthcare Research and Quality found a “moderate” strength of evidence for oral propranolol over steroids, alongside “moderate” evidence linking the beta-blocker to potential harms.
In an interview, Dr. Michael Cabana, who was not involved the studies, noted that historically, lesions were considered benign, but that management “has changed tremendously in the last few years.” Systematic reviews suggest that propranolol is “extremely effective” in treating IH, said Dr. Cabana, professor of pediatrics at the University of California, San Francisco. “But every child and every IH lesion is different. Usually, for thin, superficial IH lesions in low-risk areas, topical corticosteroids can still be useful.”
Because the early growth of IH is nonlinear and occurs fastest at about 1-2 months of age, high-risk patients should be referred to a pediatric dermatologist by age 4 weeks, Dr. Cabana said. These include patients with facial or ulcerated hemangiomas, lesions that could threaten vision or the airway, those associated with other anomalies, or lesions in the perineal area or lumbosacral area, he added. Propranolol can cause sleep disruption and cold hands and feet, he noted. Cardiovascular effects are “usually minor,” while hypoglycemia is usually the most serious ADR.
The overall rate of treatment-related hypoglycemia in the JAMA study was only 0.4%, but half these patients had hypoglycemic seizures. Hypoglycemia was “aggravated by the beta-adrenergic antagonist properties of propranolol, and worsening conditions of children who also had other concomitant diseases,” Dr. Prey and her associates said. Despite monitoring, bradycardia also occurred in patients with severe comorbidities.
“Prescribers must counsel parents at each follow-up visit to discontinue propranolol during fasting and intercurrent illness, especially in the setting of restricted oral intake and respiratory symptoms,” they emphasized.
The comparative effectiveness review included 148 studies and 15 randomized controlled trials. Few studies compared lasers and beta-blockers, but lasers historically have yielded much lower success rates than have more recent studies of propranolol, the researchers noted. Pulsed dye laser was generally more effective than were other laser modalities, with moderate strength of evidence for improvement in skin pigmentation and relatively low risk of pain.
A third study also published in January reported that infantile hemangiomas have become more common in recent decades in conjunction with declines in gestational age and birth weight (J Am Acad Dermatol. 2016 Jan;74 [1] 120-6).
Dr. Prey and her associates were funded by Pierre Fabre Dermatologie and the French Health Products Agency. She and one coinvestigator reported involvement in clinical trials of propranolol for infantile hemangioma. The other researchers had no disclosures. The systematic review was supported by the Agency for Healthcare Research and Quality, U.S. Department of Health & Human Services. The investigators had no disclosures.
FROM JAMA, PEDIATRICS, AND AHRQ
Key clinical point: Propranolol is highly effective in the treatment of infantile hemangioma, but its long-term safety merits further study.
Major finding: In a large cohort study, 84% of patients who stopped propranolol therapy did so because of “satisfactory efficacy.” In a separate meta-analysis, propranolol had the highest mean estimate of expected clearance of IH of any therapy.
Data source: An uncontrolled prospective study of 906 children with proliferative infantile hemangioma and a separate meta-analysis of 18 other studies.
Disclosures: Dr. Prey and the other authors of the cohort study were funded by Pierre Fabre Dermatologie and the French Health Products Agency. She and one coinvestigator reported involvement in clinical trials of propranolol for infantile hemangioma. The other researchers had no disclosures. The systematic review was supported by the Agency for Healthcare Research and Quality, the U.S. Department of Health & Human Services. The investigators had no disclosures.
High-dose vitamin D in pregnancy fails to prevent wheezing risk in children
Among pregnant women at high risk for having a child with asthma, high doses of vitamin D administered during the third trimester failed to prevent persistent wheezing illness in their children at age 3, according to two separate reports published online Jan. 26 in JAMA.
Both studies were conducted because vitamin D insufficiency during pregnancy is commonplace and is thought to affect fetal immune programming and to contribute to asthma pathogenesis. In addition, observational studies have found an association between low levels of vitamin D in cord blood and later asthma in the child.
The two randomized, double-blind placebo-controlled clinical trials found that neither 2,800 IU/day nor 4,400 IU/day of vitamin D significantly reduced the risk of persistent wheeze in the offspring through 3 years of age. However, both research groups noted that their studies may have been underpowered to detect a clinically important protective effect, and both recommended longer-term observation of their study participants, as well as further studies using larger sample sizes, higher doses of vitamin D, administration earlier in pregnancy, and postnatal supplementation to establish a definitive result.
In the first study – conducted as part of the Copenhagen Prospective Studies on Asthma in Childhood 2010 cohort – 623 Danish women already taking the standard 400 IU of vitamin D3 during pregnancy were randomly assigned to receive an additional 2,400 IU (315 women) or a matching placebo (308 women) from 22 to 26 weeks’ gestation until delivery. After exclusions, researchers analyzed data on 581 children.
Maternal serum vitamin D levels increased markedly in the active-treatment group. “Correspondingly, the percentage of women with sufficient levels of vitamin D (greater than 30 ng/mL) after the intervention was 81% in the vitamin D group, compared with 44% in the control group,” wrote Dr. Bo L. Chawes of Copenhagen Prospective Studies on Asthma in Childhood, University of Copenhagen, and his associates.
Persistent wheeze developed in 104 (18%) of the 581 children: 47 (16%) in the vitamin D group and 57 (20%) in the control group, a nonsignificant difference. Similarly, asthma was diagnosed in 79 children: 32 (12%) in the vitamin D group and 47 (14%) in the control group, another nonsignificant difference.
Vitamin D supplementation also made no difference in infants’ levels of C-reactive protein, interleukin-6, tumor necrosis factor–alpha, or CXCL8, nor in the number of upper respiratory tract infections (5.2 per year vs 5.3 per year), the number of lower respiratory tract infections (32% vs 33%), the risk of allergic sensitization as measured by skin prick test or specific IgE level, or the development of eczema (23% vs 25%).
However, the risk of persistent wheeze was higher in children whose mothers’ vitamin D levels were lowest, compared with those whose mothers’ vitamin D levels were in the middle and upper tertiles. And high-dose vitamin D was protective with regard to some secondary endpoints, such as preventing more episodes of “troublesome lung symptoms” (5.9 vs. 7.2).
This finding, together with the study’s somewhat reduced statistical power, mean that a clinically important protective effect cannot be ruled out. In addition, the supplementation dose may have been too low or may have been given too late in the course of pregnancy to produce a significant effect, Dr. Chawes and his associates wrote (JAMA. 2016;315[4]:353-61. doi: 10.1001/jama.2015.18318).In the second study – the Vitamin D Antenatal Asthma Reduction Trial – 876 pregnant women in Boston, St. Louis, and San Diego who were already taking the standard 400 IU of vitamin D were randomly assigned to receive either an additional 4,000 IU/day (440 participants) or a matching placebo (436 participants). Maternal levels of vitamin D rose markedly in the active-treatment group (mean, 39.2 ng/mL), compared with the control group (mean, 26.8 ng/mL), and the proportion of women who achieved higher than “inadequate” levels was much greater (74.9% vs 34.0%), reported Dr. Augusto A. Litonjua of Brigham and Women’s Hospital, Boston, and his associates.
A total of 24.3% of the vitamin D group and 30.4% of the control group developed asthma or recurrent wheeze by age 3 years, a nonsignificant difference. However, the incidence of asthma was so much lower than anticipated in both study groups that the study may have lost statistical power to detect a clinically meaningful difference, according to the investigators (JAMA. 2016;315[4]:362-70. doi: 10.1001/jama.2015.18589).
It remains unclear whether vitamin D supplementation during pregnancy will reduce asthma and persistent wheezing in the offspring. “Larger studies and longer follow-up of the children in this study will be needed to answer the question,” the investigators wrote. “If additional studies identify a significant effect, given the high prevalence of low vitamin D levels in pregnant women, the effect of this inexpensive intervention on child health could be substantial.”
The first study was supported by the Copenhagen Prospective Study on Asthma in Childhood, which is funded by private and public research groups. One of the coauthors reported receiving consulting fees from Chiesi. The Vitamin D Antenatal Asthma Reduction Trial was supported by the U.S. National Heart, Lung, and Blood Institute and the National Centers for Advancing Translational Sciences. The lead author, Dr. Litonjua, reported receiving personal fees from UpToDate and Springer Humana Press; his associates reported ties to numerous industry sources.
These are sobering findings. Even if we assume that prenatal vitamin D supplementation will prove more protective as the children in these studies grow older, vitamin D insufficiency still would explain only a small portion of the current asthma epidemic.
But neither study showed any unwanted effects from supplementation, so it seems reasonable for clinicians to prescribe vitamin D to mothers at high risk of having children with asthma by virtue of their own asthma, eczema, or allergic rhinitis – especially if those mothers are deficient in vitamin D. However, the data in these two clinical trials do not support the use of very high-dose vitamin D, since any beneficial effects achieved with 4,400 IU/day were identical to those achieved with approximately half as high a dose.
Dr. Erika von Mutius is at Ludwig Maximilians University, Munich. Dr. Fernando D. Martinez is at the asthma and airway disease research center and the department of pediatrics at the University of Arizona, Tucson. Both reported having no relevant financial disclosures. Their remarks are adapted from an editorial accompanying the two reports (JAMA 2016;315[4]:347-8.).
These are sobering findings. Even if we assume that prenatal vitamin D supplementation will prove more protective as the children in these studies grow older, vitamin D insufficiency still would explain only a small portion of the current asthma epidemic.
But neither study showed any unwanted effects from supplementation, so it seems reasonable for clinicians to prescribe vitamin D to mothers at high risk of having children with asthma by virtue of their own asthma, eczema, or allergic rhinitis – especially if those mothers are deficient in vitamin D. However, the data in these two clinical trials do not support the use of very high-dose vitamin D, since any beneficial effects achieved with 4,400 IU/day were identical to those achieved with approximately half as high a dose.
Dr. Erika von Mutius is at Ludwig Maximilians University, Munich. Dr. Fernando D. Martinez is at the asthma and airway disease research center and the department of pediatrics at the University of Arizona, Tucson. Both reported having no relevant financial disclosures. Their remarks are adapted from an editorial accompanying the two reports (JAMA 2016;315[4]:347-8.).
These are sobering findings. Even if we assume that prenatal vitamin D supplementation will prove more protective as the children in these studies grow older, vitamin D insufficiency still would explain only a small portion of the current asthma epidemic.
But neither study showed any unwanted effects from supplementation, so it seems reasonable for clinicians to prescribe vitamin D to mothers at high risk of having children with asthma by virtue of their own asthma, eczema, or allergic rhinitis – especially if those mothers are deficient in vitamin D. However, the data in these two clinical trials do not support the use of very high-dose vitamin D, since any beneficial effects achieved with 4,400 IU/day were identical to those achieved with approximately half as high a dose.
Dr. Erika von Mutius is at Ludwig Maximilians University, Munich. Dr. Fernando D. Martinez is at the asthma and airway disease research center and the department of pediatrics at the University of Arizona, Tucson. Both reported having no relevant financial disclosures. Their remarks are adapted from an editorial accompanying the two reports (JAMA 2016;315[4]:347-8.).
Among pregnant women at high risk for having a child with asthma, high doses of vitamin D administered during the third trimester failed to prevent persistent wheezing illness in their children at age 3, according to two separate reports published online Jan. 26 in JAMA.
Both studies were conducted because vitamin D insufficiency during pregnancy is commonplace and is thought to affect fetal immune programming and to contribute to asthma pathogenesis. In addition, observational studies have found an association between low levels of vitamin D in cord blood and later asthma in the child.
The two randomized, double-blind placebo-controlled clinical trials found that neither 2,800 IU/day nor 4,400 IU/day of vitamin D significantly reduced the risk of persistent wheeze in the offspring through 3 years of age. However, both research groups noted that their studies may have been underpowered to detect a clinically important protective effect, and both recommended longer-term observation of their study participants, as well as further studies using larger sample sizes, higher doses of vitamin D, administration earlier in pregnancy, and postnatal supplementation to establish a definitive result.
In the first study – conducted as part of the Copenhagen Prospective Studies on Asthma in Childhood 2010 cohort – 623 Danish women already taking the standard 400 IU of vitamin D3 during pregnancy were randomly assigned to receive an additional 2,400 IU (315 women) or a matching placebo (308 women) from 22 to 26 weeks’ gestation until delivery. After exclusions, researchers analyzed data on 581 children.
Maternal serum vitamin D levels increased markedly in the active-treatment group. “Correspondingly, the percentage of women with sufficient levels of vitamin D (greater than 30 ng/mL) after the intervention was 81% in the vitamin D group, compared with 44% in the control group,” wrote Dr. Bo L. Chawes of Copenhagen Prospective Studies on Asthma in Childhood, University of Copenhagen, and his associates.
Persistent wheeze developed in 104 (18%) of the 581 children: 47 (16%) in the vitamin D group and 57 (20%) in the control group, a nonsignificant difference. Similarly, asthma was diagnosed in 79 children: 32 (12%) in the vitamin D group and 47 (14%) in the control group, another nonsignificant difference.
Vitamin D supplementation also made no difference in infants’ levels of C-reactive protein, interleukin-6, tumor necrosis factor–alpha, or CXCL8, nor in the number of upper respiratory tract infections (5.2 per year vs 5.3 per year), the number of lower respiratory tract infections (32% vs 33%), the risk of allergic sensitization as measured by skin prick test or specific IgE level, or the development of eczema (23% vs 25%).
However, the risk of persistent wheeze was higher in children whose mothers’ vitamin D levels were lowest, compared with those whose mothers’ vitamin D levels were in the middle and upper tertiles. And high-dose vitamin D was protective with regard to some secondary endpoints, such as preventing more episodes of “troublesome lung symptoms” (5.9 vs. 7.2).
This finding, together with the study’s somewhat reduced statistical power, mean that a clinically important protective effect cannot be ruled out. In addition, the supplementation dose may have been too low or may have been given too late in the course of pregnancy to produce a significant effect, Dr. Chawes and his associates wrote (JAMA. 2016;315[4]:353-61. doi: 10.1001/jama.2015.18318).In the second study – the Vitamin D Antenatal Asthma Reduction Trial – 876 pregnant women in Boston, St. Louis, and San Diego who were already taking the standard 400 IU of vitamin D were randomly assigned to receive either an additional 4,000 IU/day (440 participants) or a matching placebo (436 participants). Maternal levels of vitamin D rose markedly in the active-treatment group (mean, 39.2 ng/mL), compared with the control group (mean, 26.8 ng/mL), and the proportion of women who achieved higher than “inadequate” levels was much greater (74.9% vs 34.0%), reported Dr. Augusto A. Litonjua of Brigham and Women’s Hospital, Boston, and his associates.
A total of 24.3% of the vitamin D group and 30.4% of the control group developed asthma or recurrent wheeze by age 3 years, a nonsignificant difference. However, the incidence of asthma was so much lower than anticipated in both study groups that the study may have lost statistical power to detect a clinically meaningful difference, according to the investigators (JAMA. 2016;315[4]:362-70. doi: 10.1001/jama.2015.18589).
It remains unclear whether vitamin D supplementation during pregnancy will reduce asthma and persistent wheezing in the offspring. “Larger studies and longer follow-up of the children in this study will be needed to answer the question,” the investigators wrote. “If additional studies identify a significant effect, given the high prevalence of low vitamin D levels in pregnant women, the effect of this inexpensive intervention on child health could be substantial.”
The first study was supported by the Copenhagen Prospective Study on Asthma in Childhood, which is funded by private and public research groups. One of the coauthors reported receiving consulting fees from Chiesi. The Vitamin D Antenatal Asthma Reduction Trial was supported by the U.S. National Heart, Lung, and Blood Institute and the National Centers for Advancing Translational Sciences. The lead author, Dr. Litonjua, reported receiving personal fees from UpToDate and Springer Humana Press; his associates reported ties to numerous industry sources.
Among pregnant women at high risk for having a child with asthma, high doses of vitamin D administered during the third trimester failed to prevent persistent wheezing illness in their children at age 3, according to two separate reports published online Jan. 26 in JAMA.
Both studies were conducted because vitamin D insufficiency during pregnancy is commonplace and is thought to affect fetal immune programming and to contribute to asthma pathogenesis. In addition, observational studies have found an association between low levels of vitamin D in cord blood and later asthma in the child.
The two randomized, double-blind placebo-controlled clinical trials found that neither 2,800 IU/day nor 4,400 IU/day of vitamin D significantly reduced the risk of persistent wheeze in the offspring through 3 years of age. However, both research groups noted that their studies may have been underpowered to detect a clinically important protective effect, and both recommended longer-term observation of their study participants, as well as further studies using larger sample sizes, higher doses of vitamin D, administration earlier in pregnancy, and postnatal supplementation to establish a definitive result.
In the first study – conducted as part of the Copenhagen Prospective Studies on Asthma in Childhood 2010 cohort – 623 Danish women already taking the standard 400 IU of vitamin D3 during pregnancy were randomly assigned to receive an additional 2,400 IU (315 women) or a matching placebo (308 women) from 22 to 26 weeks’ gestation until delivery. After exclusions, researchers analyzed data on 581 children.
Maternal serum vitamin D levels increased markedly in the active-treatment group. “Correspondingly, the percentage of women with sufficient levels of vitamin D (greater than 30 ng/mL) after the intervention was 81% in the vitamin D group, compared with 44% in the control group,” wrote Dr. Bo L. Chawes of Copenhagen Prospective Studies on Asthma in Childhood, University of Copenhagen, and his associates.
Persistent wheeze developed in 104 (18%) of the 581 children: 47 (16%) in the vitamin D group and 57 (20%) in the control group, a nonsignificant difference. Similarly, asthma was diagnosed in 79 children: 32 (12%) in the vitamin D group and 47 (14%) in the control group, another nonsignificant difference.
Vitamin D supplementation also made no difference in infants’ levels of C-reactive protein, interleukin-6, tumor necrosis factor–alpha, or CXCL8, nor in the number of upper respiratory tract infections (5.2 per year vs 5.3 per year), the number of lower respiratory tract infections (32% vs 33%), the risk of allergic sensitization as measured by skin prick test or specific IgE level, or the development of eczema (23% vs 25%).
However, the risk of persistent wheeze was higher in children whose mothers’ vitamin D levels were lowest, compared with those whose mothers’ vitamin D levels were in the middle and upper tertiles. And high-dose vitamin D was protective with regard to some secondary endpoints, such as preventing more episodes of “troublesome lung symptoms” (5.9 vs. 7.2).
This finding, together with the study’s somewhat reduced statistical power, mean that a clinically important protective effect cannot be ruled out. In addition, the supplementation dose may have been too low or may have been given too late in the course of pregnancy to produce a significant effect, Dr. Chawes and his associates wrote (JAMA. 2016;315[4]:353-61. doi: 10.1001/jama.2015.18318).In the second study – the Vitamin D Antenatal Asthma Reduction Trial – 876 pregnant women in Boston, St. Louis, and San Diego who were already taking the standard 400 IU of vitamin D were randomly assigned to receive either an additional 4,000 IU/day (440 participants) or a matching placebo (436 participants). Maternal levels of vitamin D rose markedly in the active-treatment group (mean, 39.2 ng/mL), compared with the control group (mean, 26.8 ng/mL), and the proportion of women who achieved higher than “inadequate” levels was much greater (74.9% vs 34.0%), reported Dr. Augusto A. Litonjua of Brigham and Women’s Hospital, Boston, and his associates.
A total of 24.3% of the vitamin D group and 30.4% of the control group developed asthma or recurrent wheeze by age 3 years, a nonsignificant difference. However, the incidence of asthma was so much lower than anticipated in both study groups that the study may have lost statistical power to detect a clinically meaningful difference, according to the investigators (JAMA. 2016;315[4]:362-70. doi: 10.1001/jama.2015.18589).
It remains unclear whether vitamin D supplementation during pregnancy will reduce asthma and persistent wheezing in the offspring. “Larger studies and longer follow-up of the children in this study will be needed to answer the question,” the investigators wrote. “If additional studies identify a significant effect, given the high prevalence of low vitamin D levels in pregnant women, the effect of this inexpensive intervention on child health could be substantial.”
The first study was supported by the Copenhagen Prospective Study on Asthma in Childhood, which is funded by private and public research groups. One of the coauthors reported receiving consulting fees from Chiesi. The Vitamin D Antenatal Asthma Reduction Trial was supported by the U.S. National Heart, Lung, and Blood Institute and the National Centers for Advancing Translational Sciences. The lead author, Dr. Litonjua, reported receiving personal fees from UpToDate and Springer Humana Press; his associates reported ties to numerous industry sources.
FROM JAMA
Key clinical point: High doses of vitamin D administered during the third trimester didn’t prevent wheezing in children at age 3.
Major finding: In a study of 581 children, persistent wheeze developed in 16% in the vitamin D group and in 20% in the control group. In a separate trial of 806 infants, there was a 6.1% reduction in asthma or recurrent wheezing at age 3, which was not statistically significant.
Data source: Two separate randomized, double-blind placebo-controlled trials involving a total of nearly 1,500 pregnant women.
Disclosures: The first study was supported by the Copenhagen Prospective Study on Asthma in Childhood, which is funded by private and public research groups. One of the coauthors reported receiving consulting fees from Chiesi. The Vitamin D Antenatal Asthma Reduction Trial was supported by the U.S. National Heart, Lung, and Blood Institute and the National Centers for Advancing Translational Sciences. The lead author, Dr. Litonjua, reported receiving personal fees from UpToDate and Springer Humana Press; his associates reported ties to numerous industry sources.
Race plays role in Hodgkin lymphoma outcomes in kids
Photo courtesy of Sylvester
Comprehensive Cancer Center
In a retrospective study, young African American patients with Hodgkin lymphoma (HL) had inferior long-term overall survival when compared to their Hispanic and white peers.
Hispanic and white patients had similar rates of overall survival, but Hispanic males had inferior disease-specific survival compared to white males.
The study, published in Pediatric Blood & Cancer, is the largest yet on racial and ethnic disparity in the pediatric HL population in the US.
“Little was known about the association between race, ethnicity, and survival in the pediatric Hodgkin lymphoma population,” said Joseph Panoff, MD, of Sylvester Comprehensive Cancer Center at the University of Miami in Florida.
“Our study showed that African American children and teenagers had worse overall survival than whites and Hispanics at 25 years after diagnosis. We also found that Hispanic males had inferior disease-specific survival compared to white males.”
Dr Panoff and his colleagues analyzed data from more than 7800 patients listed in the Florida Cancer Data System (FCDS) and the National Institutes of Health’s Surveillance, Epidemiology, and End Results Program (SEER).
The patients were 0.1 to 21 years of age (average, 17 years) and were diagnosed with HL from 1981 to 2010.
In the FCDS cohort, which was significantly smaller than the SEER cohort (1778 vs 6027), African Americans had a 33% overall survival rate at 25 years, compared to 44.7% for Hispanics and 49.2% for whites (P=0.0005).
In a multivariate analysis, African American race was associated with inferior overall survival. The hazard ratio was 1.81 (P=0.0003).
Patients in the FCDS cohort had worse overall survival than patients in the SEER cohort, indicating that patients treated in Florida have worse outcomes when compared to the rest of the nation.
In the SEER cohort, the overall survival rate at 25 years was 74.2% for African Americans and 82% for both Hispanic and white patients (P=0.0005). Disease-specific survival rates at 25 years were 85.7% for African Americans, 88.1% for Hispanics, and 90.8% for whites (P=0.0002).
The researchers noted that Hispanic males had inferior disease-specific survival when compared to white males—84.8% and 90.6%, respectively (P=0.0478).
And Hispanic race was a predictor of inferior disease-specific survival in multivariate analysis. The hazard ratio was 1.238 (P<0.0001).
“Clearly, racial and ethnic disparities persist in the pediatric Hodgkin lymphoma population, despite modern treatment, particularly in Florida,” Dr Panoff noted. “The underlying causes of these disparities are complex and need further explanation.”
As a next step, Dr Panoff suggests identifying flaws in the diagnostic and treatment process with regard to African American and Hispanic patients.
“It is important to identify sociocultural factors and health behaviors that negatively affect overall survival in African American patients and disease-free survival in Hispanic males,” he said. “The fact that the entire Florida cohort seems to have worse overall survival than patients in the rest of the country is a new finding that requires further research.” 
Photo courtesy of Sylvester
Comprehensive Cancer Center
In a retrospective study, young African American patients with Hodgkin lymphoma (HL) had inferior long-term overall survival when compared to their Hispanic and white peers.
Hispanic and white patients had similar rates of overall survival, but Hispanic males had inferior disease-specific survival compared to white males.
The study, published in Pediatric Blood & Cancer, is the largest yet on racial and ethnic disparity in the pediatric HL population in the US.
“Little was known about the association between race, ethnicity, and survival in the pediatric Hodgkin lymphoma population,” said Joseph Panoff, MD, of Sylvester Comprehensive Cancer Center at the University of Miami in Florida.
“Our study showed that African American children and teenagers had worse overall survival than whites and Hispanics at 25 years after diagnosis. We also found that Hispanic males had inferior disease-specific survival compared to white males.”
Dr Panoff and his colleagues analyzed data from more than 7800 patients listed in the Florida Cancer Data System (FCDS) and the National Institutes of Health’s Surveillance, Epidemiology, and End Results Program (SEER).
The patients were 0.1 to 21 years of age (average, 17 years) and were diagnosed with HL from 1981 to 2010.
In the FCDS cohort, which was significantly smaller than the SEER cohort (1778 vs 6027), African Americans had a 33% overall survival rate at 25 years, compared to 44.7% for Hispanics and 49.2% for whites (P=0.0005).
In a multivariate analysis, African American race was associated with inferior overall survival. The hazard ratio was 1.81 (P=0.0003).
Patients in the FCDS cohort had worse overall survival than patients in the SEER cohort, indicating that patients treated in Florida have worse outcomes when compared to the rest of the nation.
In the SEER cohort, the overall survival rate at 25 years was 74.2% for African Americans and 82% for both Hispanic and white patients (P=0.0005). Disease-specific survival rates at 25 years were 85.7% for African Americans, 88.1% for Hispanics, and 90.8% for whites (P=0.0002).
The researchers noted that Hispanic males had inferior disease-specific survival when compared to white males—84.8% and 90.6%, respectively (P=0.0478).
And Hispanic race was a predictor of inferior disease-specific survival in multivariate analysis. The hazard ratio was 1.238 (P<0.0001).
“Clearly, racial and ethnic disparities persist in the pediatric Hodgkin lymphoma population, despite modern treatment, particularly in Florida,” Dr Panoff noted. “The underlying causes of these disparities are complex and need further explanation.”
As a next step, Dr Panoff suggests identifying flaws in the diagnostic and treatment process with regard to African American and Hispanic patients.
“It is important to identify sociocultural factors and health behaviors that negatively affect overall survival in African American patients and disease-free survival in Hispanic males,” he said. “The fact that the entire Florida cohort seems to have worse overall survival than patients in the rest of the country is a new finding that requires further research.”
Photo courtesy of Sylvester
Comprehensive Cancer Center
In a retrospective study, young African American patients with Hodgkin lymphoma (HL) had inferior long-term overall survival when compared to their Hispanic and white peers.
Hispanic and white patients had similar rates of overall survival, but Hispanic males had inferior disease-specific survival compared to white males.
The study, published in Pediatric Blood & Cancer, is the largest yet on racial and ethnic disparity in the pediatric HL population in the US.
“Little was known about the association between race, ethnicity, and survival in the pediatric Hodgkin lymphoma population,” said Joseph Panoff, MD, of Sylvester Comprehensive Cancer Center at the University of Miami in Florida.
“Our study showed that African American children and teenagers had worse overall survival than whites and Hispanics at 25 years after diagnosis. We also found that Hispanic males had inferior disease-specific survival compared to white males.”
Dr Panoff and his colleagues analyzed data from more than 7800 patients listed in the Florida Cancer Data System (FCDS) and the National Institutes of Health’s Surveillance, Epidemiology, and End Results Program (SEER).
The patients were 0.1 to 21 years of age (average, 17 years) and were diagnosed with HL from 1981 to 2010.
In the FCDS cohort, which was significantly smaller than the SEER cohort (1778 vs 6027), African Americans had a 33% overall survival rate at 25 years, compared to 44.7% for Hispanics and 49.2% for whites (P=0.0005).
In a multivariate analysis, African American race was associated with inferior overall survival. The hazard ratio was 1.81 (P=0.0003).
Patients in the FCDS cohort had worse overall survival than patients in the SEER cohort, indicating that patients treated in Florida have worse outcomes when compared to the rest of the nation.
In the SEER cohort, the overall survival rate at 25 years was 74.2% for African Americans and 82% for both Hispanic and white patients (P=0.0005). Disease-specific survival rates at 25 years were 85.7% for African Americans, 88.1% for Hispanics, and 90.8% for whites (P=0.0002).
The researchers noted that Hispanic males had inferior disease-specific survival when compared to white males—84.8% and 90.6%, respectively (P=0.0478).
And Hispanic race was a predictor of inferior disease-specific survival in multivariate analysis. The hazard ratio was 1.238 (P<0.0001).
“Clearly, racial and ethnic disparities persist in the pediatric Hodgkin lymphoma population, despite modern treatment, particularly in Florida,” Dr Panoff noted. “The underlying causes of these disparities are complex and need further explanation.”
As a next step, Dr Panoff suggests identifying flaws in the diagnostic and treatment process with regard to African American and Hispanic patients.
“It is important to identify sociocultural factors and health behaviors that negatively affect overall survival in African American patients and disease-free survival in Hispanic males,” he said. “The fact that the entire Florida cohort seems to have worse overall survival than patients in the rest of the country is a new finding that requires further research.”