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Contact dermatitis in children: The top 10 allergens
Contact dermatitis should be suspected in patients with eczematous dermatitis atypical in location, geometric or symmetric in distribution, or unresponsive to or worsened by common therapies, Dr. Catalina Matiz emphasized.
Allergic contact dermatitis is a complex disorder characterized by a type IV delayed-type hypersensitivity reaction that occurs when a patient’s skin is exposed to a substance easily penetrates the skin barrier.
Increasingly recognized in the United States, many pediatric patients are becoming sensitized to contact allergens found in personal care products, including skin care products, topical medications, and clothing.
A study published by Hill et al. in 2016 reviewed pediatric patch test studies to determine the top contact allergens in children (Expert Rev Clin Immunol. 2016;12[5]:551-61).
Dr. Matiz presented the top 10 allergens discovered by this group, and offered practical advice for allergen avoidance.
Topping the list in descending order are the following:
- Tixocortol pivalate (a corticosteroid).
- Propylene glycol.
- Methylchloroisothiazolinone (MCI)/methylisothiazolinone (MI).
- Formaldehyde.
- Cocamidopropyl betaine.
- Lanolin.
- Benzalkonium chloride.
- Fragrance and balsam of peru.
- Neomycin.
- Nickel.
Dr. Matiz educated meeting attendees on allergen-containing products and clinical correlations suggestive of allergic sensitization to common allergens. Tixocortol pivilate is a corticosteroid present in Class A corticosteroids including hydrocortisone acetate. She highlighted the cross reactivity between class A and class D2 corticosteroids including hydrocortisone butyrate and valerate.
“Usually topical corticosteroid–contact sensitivity manifests as a failure to improve or worsening of existing dermatitis,” emphasized Dr. Matiz of departments of dermatology and pediatrics at the university.
Propylene glycol, benzalkonium chloride, and neomycin also represent top contact allergens frequently found in topical medications. Similarly, lanolin contact sensitivity often presents as refractory or worsening atopic dermatitis. “Lanolin, also known as wool alcohol, is commonly found in emollients, medications, and personal care products used by atopic dermatitis patients,” Dr. Matiz stressed.
Methylchloroisothiazolinone/methylisothiazolinone represent preservatives commonly found in wet wipes, hypoallergenic, and sensitive skin products. This was the allergen of the year in 2013 and was subsequently removed from many wet wipe formulations and products in response.
In addition to acute management of allergic contact dermatitis with corticosteroids, Dr. Matiz further emphasized the importance of preemptive avoidance of the top ten allergens.
She recommends patch testing if no clinical improvement is evident after 8 weeks of common allergen avoidance, for definitive allergen identification.
Dr. Matiz said she had no relevant financial disclosures.
Contact dermatitis should be suspected in patients with eczematous dermatitis atypical in location, geometric or symmetric in distribution, or unresponsive to or worsened by common therapies, Dr. Catalina Matiz emphasized.
Allergic contact dermatitis is a complex disorder characterized by a type IV delayed-type hypersensitivity reaction that occurs when a patient’s skin is exposed to a substance easily penetrates the skin barrier.
Increasingly recognized in the United States, many pediatric patients are becoming sensitized to contact allergens found in personal care products, including skin care products, topical medications, and clothing.
A study published by Hill et al. in 2016 reviewed pediatric patch test studies to determine the top contact allergens in children (Expert Rev Clin Immunol. 2016;12[5]:551-61).
Dr. Matiz presented the top 10 allergens discovered by this group, and offered practical advice for allergen avoidance.
Topping the list in descending order are the following:
- Tixocortol pivalate (a corticosteroid).
- Propylene glycol.
- Methylchloroisothiazolinone (MCI)/methylisothiazolinone (MI).
- Formaldehyde.
- Cocamidopropyl betaine.
- Lanolin.
- Benzalkonium chloride.
- Fragrance and balsam of peru.
- Neomycin.
- Nickel.
Dr. Matiz educated meeting attendees on allergen-containing products and clinical correlations suggestive of allergic sensitization to common allergens. Tixocortol pivilate is a corticosteroid present in Class A corticosteroids including hydrocortisone acetate. She highlighted the cross reactivity between class A and class D2 corticosteroids including hydrocortisone butyrate and valerate.
“Usually topical corticosteroid–contact sensitivity manifests as a failure to improve or worsening of existing dermatitis,” emphasized Dr. Matiz of departments of dermatology and pediatrics at the university.
Propylene glycol, benzalkonium chloride, and neomycin also represent top contact allergens frequently found in topical medications. Similarly, lanolin contact sensitivity often presents as refractory or worsening atopic dermatitis. “Lanolin, also known as wool alcohol, is commonly found in emollients, medications, and personal care products used by atopic dermatitis patients,” Dr. Matiz stressed.
Methylchloroisothiazolinone/methylisothiazolinone represent preservatives commonly found in wet wipes, hypoallergenic, and sensitive skin products. This was the allergen of the year in 2013 and was subsequently removed from many wet wipe formulations and products in response.
In addition to acute management of allergic contact dermatitis with corticosteroids, Dr. Matiz further emphasized the importance of preemptive avoidance of the top ten allergens.
She recommends patch testing if no clinical improvement is evident after 8 weeks of common allergen avoidance, for definitive allergen identification.
Dr. Matiz said she had no relevant financial disclosures.
Contact dermatitis should be suspected in patients with eczematous dermatitis atypical in location, geometric or symmetric in distribution, or unresponsive to or worsened by common therapies, Dr. Catalina Matiz emphasized.
Allergic contact dermatitis is a complex disorder characterized by a type IV delayed-type hypersensitivity reaction that occurs when a patient’s skin is exposed to a substance easily penetrates the skin barrier.
Increasingly recognized in the United States, many pediatric patients are becoming sensitized to contact allergens found in personal care products, including skin care products, topical medications, and clothing.
A study published by Hill et al. in 2016 reviewed pediatric patch test studies to determine the top contact allergens in children (Expert Rev Clin Immunol. 2016;12[5]:551-61).
Dr. Matiz presented the top 10 allergens discovered by this group, and offered practical advice for allergen avoidance.
Topping the list in descending order are the following:
- Tixocortol pivalate (a corticosteroid).
- Propylene glycol.
- Methylchloroisothiazolinone (MCI)/methylisothiazolinone (MI).
- Formaldehyde.
- Cocamidopropyl betaine.
- Lanolin.
- Benzalkonium chloride.
- Fragrance and balsam of peru.
- Neomycin.
- Nickel.
Dr. Matiz educated meeting attendees on allergen-containing products and clinical correlations suggestive of allergic sensitization to common allergens. Tixocortol pivilate is a corticosteroid present in Class A corticosteroids including hydrocortisone acetate. She highlighted the cross reactivity between class A and class D2 corticosteroids including hydrocortisone butyrate and valerate.
“Usually topical corticosteroid–contact sensitivity manifests as a failure to improve or worsening of existing dermatitis,” emphasized Dr. Matiz of departments of dermatology and pediatrics at the university.
Propylene glycol, benzalkonium chloride, and neomycin also represent top contact allergens frequently found in topical medications. Similarly, lanolin contact sensitivity often presents as refractory or worsening atopic dermatitis. “Lanolin, also known as wool alcohol, is commonly found in emollients, medications, and personal care products used by atopic dermatitis patients,” Dr. Matiz stressed.
Methylchloroisothiazolinone/methylisothiazolinone represent preservatives commonly found in wet wipes, hypoallergenic, and sensitive skin products. This was the allergen of the year in 2013 and was subsequently removed from many wet wipe formulations and products in response.
In addition to acute management of allergic contact dermatitis with corticosteroids, Dr. Matiz further emphasized the importance of preemptive avoidance of the top ten allergens.
She recommends patch testing if no clinical improvement is evident after 8 weeks of common allergen avoidance, for definitive allergen identification.
Dr. Matiz said she had no relevant financial disclosures.
Molecular tests for GAS pharyngitis could spur overuse of antibiotics
SAN FRANCISCO – The diagnosis of pharyngitis due to infection by group A streptococcus (GAS) based on the detection of nucleic acid is fast and accurate. But this benefit brings the possibility of overuse of antibiotics, with treatment offered to those who, in the era of growth-based detection of the bacteria, would not have received treatment, according to Robert R. Tanz, MD.
Dr. Tanz, professor of pediatrics at Northwestern University, Chicago, delivered this cautionary note at the meeting of the Pediatrics Academics Societies.
“The short turnaround time, high sensitivity, and high specificity of newer molecular tests for GAS will make their use increasingly common. Many of the additional patients identified by molecular testing may not have an illness attributable to GAS. The increase in positive tests will probably be associated with increased antibiotic prescribing. This may not be beneficial, especially in areas with low rates of acute rheumatic fever,” said Dr. Tanz, who practices at Ann & Robert Lurie Children’s Hospital of Chicago.
Nowadays, diagnosis of GAS at Ann & Robert Lurie Children’s Hospital uses the Illumigene system. Its use has been approved by the Food and Drug Administration for diagnosis without the need for backup culture of throat swabs. Results are available in about 1 hour.
Dr. Tanz and his colleagues took a retrospective look at patient records during 2013, when testing was still growth-based, and in 2014 and 2015, after the hospital had shifted to the molecular analysis of throat swabs. The aim was to determine the proportion of tests positive for GAS prior to and after the switch.
The positive detection rate of 9.6% (96 of 997 samples) in 2013 climbed to 17% (152 of 894) in 2014 and 16% (138 of 859) in 2015. The difference was highly significant (P less than .00001).
Sore throats increase in the colder months when people tend to be indoors more often, and this seasonality was evident in 2013. However, detection was more consistent throughout the 12 months in 2014 (2013 vs 2014, P less than .000001) and 2015 (2013 vs 2015, P less than .00001). The detection rates in 2014 and 2015 were similar (P equal to .59), according to Dr. Tanz.
The new era of molecular testing circumvents what is known as the spectrum effect, in which culture-based tests are more often positive in patients with symptoms that are consistent with the infection, he said. In contrast, molecular tests can increase the identification of the target bacterium, here GAS, in patients who have sore throat caused by a viral infection.
Preliminary results presented by Dr. Tanz indicated a significantly greater detection of GAS in children not displaying symptoms of infection. In decades past, these children would not have been treated.
“The increase in positive tests for group A strep is likely associated with increased antibiotic prescribing. This may or may not represent a benefit to patients, as the additional identified patients may not have an illness actually attributable to group A strep,” said Dr. Tanz.
“Our findings support rigorous selectivity in choosing which patients to test, specifically excluding those with overt viral symptoms, as recommended in the guidelines from the [Infectious Diseases Society of America], [American Academy of Pediatrics], and other groups,” he said, adding that clinician guidance on the use of molecular diagnostic tests for pharyngitis caused by group A strep is a prudent step.
Features suggestive of GAS may include sudden onset of sore throat, age 5-15 years, fever, headache, nausea, vomiting, and abdominal pain, tonsillopharyngeal inflammation and patchy tonsillopharyngeal exudates, palatal petechiae, tender nodes, and scarlatiniform rash. Viral pharyngitis features include conjunctivitis, coryza, cough, diarrhea, discrete ulcerative stomatitis, viral exanthema, and hoarseness, according to the 2012 Infectious Diseases Society of American guidelines (Clin Infect Dis. 2012. doi: 10.1093/cid/cis629).
For most people, a sore throat is more of a temporary inconvenience rather than a looming health threat, but GAS easily spreads from person to person and can lead to the more serious condition of acute rheumatic fever, Dr. Tanz said. Hence the concern with diagnosing the cause of sore throat and, when the cause is bacterial, alleviating the infection using antibiotics.
The study was conducted at Ann & Robert H. Lurie Children’s Hospital of Chicago and was not funded. Dr. Tanz reported having received support from Meridian Bioscience, manufacturer of the Illumigene Group A Streptococcus assay. Meridian Bioscience did not support this study.
SAN FRANCISCO – The diagnosis of pharyngitis due to infection by group A streptococcus (GAS) based on the detection of nucleic acid is fast and accurate. But this benefit brings the possibility of overuse of antibiotics, with treatment offered to those who, in the era of growth-based detection of the bacteria, would not have received treatment, according to Robert R. Tanz, MD.
Dr. Tanz, professor of pediatrics at Northwestern University, Chicago, delivered this cautionary note at the meeting of the Pediatrics Academics Societies.
“The short turnaround time, high sensitivity, and high specificity of newer molecular tests for GAS will make their use increasingly common. Many of the additional patients identified by molecular testing may not have an illness attributable to GAS. The increase in positive tests will probably be associated with increased antibiotic prescribing. This may not be beneficial, especially in areas with low rates of acute rheumatic fever,” said Dr. Tanz, who practices at Ann & Robert Lurie Children’s Hospital of Chicago.
Nowadays, diagnosis of GAS at Ann & Robert Lurie Children’s Hospital uses the Illumigene system. Its use has been approved by the Food and Drug Administration for diagnosis without the need for backup culture of throat swabs. Results are available in about 1 hour.
Dr. Tanz and his colleagues took a retrospective look at patient records during 2013, when testing was still growth-based, and in 2014 and 2015, after the hospital had shifted to the molecular analysis of throat swabs. The aim was to determine the proportion of tests positive for GAS prior to and after the switch.
The positive detection rate of 9.6% (96 of 997 samples) in 2013 climbed to 17% (152 of 894) in 2014 and 16% (138 of 859) in 2015. The difference was highly significant (P less than .00001).
Sore throats increase in the colder months when people tend to be indoors more often, and this seasonality was evident in 2013. However, detection was more consistent throughout the 12 months in 2014 (2013 vs 2014, P less than .000001) and 2015 (2013 vs 2015, P less than .00001). The detection rates in 2014 and 2015 were similar (P equal to .59), according to Dr. Tanz.
The new era of molecular testing circumvents what is known as the spectrum effect, in which culture-based tests are more often positive in patients with symptoms that are consistent with the infection, he said. In contrast, molecular tests can increase the identification of the target bacterium, here GAS, in patients who have sore throat caused by a viral infection.
Preliminary results presented by Dr. Tanz indicated a significantly greater detection of GAS in children not displaying symptoms of infection. In decades past, these children would not have been treated.
“The increase in positive tests for group A strep is likely associated with increased antibiotic prescribing. This may or may not represent a benefit to patients, as the additional identified patients may not have an illness actually attributable to group A strep,” said Dr. Tanz.
“Our findings support rigorous selectivity in choosing which patients to test, specifically excluding those with overt viral symptoms, as recommended in the guidelines from the [Infectious Diseases Society of America], [American Academy of Pediatrics], and other groups,” he said, adding that clinician guidance on the use of molecular diagnostic tests for pharyngitis caused by group A strep is a prudent step.
Features suggestive of GAS may include sudden onset of sore throat, age 5-15 years, fever, headache, nausea, vomiting, and abdominal pain, tonsillopharyngeal inflammation and patchy tonsillopharyngeal exudates, palatal petechiae, tender nodes, and scarlatiniform rash. Viral pharyngitis features include conjunctivitis, coryza, cough, diarrhea, discrete ulcerative stomatitis, viral exanthema, and hoarseness, according to the 2012 Infectious Diseases Society of American guidelines (Clin Infect Dis. 2012. doi: 10.1093/cid/cis629).
For most people, a sore throat is more of a temporary inconvenience rather than a looming health threat, but GAS easily spreads from person to person and can lead to the more serious condition of acute rheumatic fever, Dr. Tanz said. Hence the concern with diagnosing the cause of sore throat and, when the cause is bacterial, alleviating the infection using antibiotics.
The study was conducted at Ann & Robert H. Lurie Children’s Hospital of Chicago and was not funded. Dr. Tanz reported having received support from Meridian Bioscience, manufacturer of the Illumigene Group A Streptococcus assay. Meridian Bioscience did not support this study.
SAN FRANCISCO – The diagnosis of pharyngitis due to infection by group A streptococcus (GAS) based on the detection of nucleic acid is fast and accurate. But this benefit brings the possibility of overuse of antibiotics, with treatment offered to those who, in the era of growth-based detection of the bacteria, would not have received treatment, according to Robert R. Tanz, MD.
Dr. Tanz, professor of pediatrics at Northwestern University, Chicago, delivered this cautionary note at the meeting of the Pediatrics Academics Societies.
“The short turnaround time, high sensitivity, and high specificity of newer molecular tests for GAS will make their use increasingly common. Many of the additional patients identified by molecular testing may not have an illness attributable to GAS. The increase in positive tests will probably be associated with increased antibiotic prescribing. This may not be beneficial, especially in areas with low rates of acute rheumatic fever,” said Dr. Tanz, who practices at Ann & Robert Lurie Children’s Hospital of Chicago.
Nowadays, diagnosis of GAS at Ann & Robert Lurie Children’s Hospital uses the Illumigene system. Its use has been approved by the Food and Drug Administration for diagnosis without the need for backup culture of throat swabs. Results are available in about 1 hour.
Dr. Tanz and his colleagues took a retrospective look at patient records during 2013, when testing was still growth-based, and in 2014 and 2015, after the hospital had shifted to the molecular analysis of throat swabs. The aim was to determine the proportion of tests positive for GAS prior to and after the switch.
The positive detection rate of 9.6% (96 of 997 samples) in 2013 climbed to 17% (152 of 894) in 2014 and 16% (138 of 859) in 2015. The difference was highly significant (P less than .00001).
Sore throats increase in the colder months when people tend to be indoors more often, and this seasonality was evident in 2013. However, detection was more consistent throughout the 12 months in 2014 (2013 vs 2014, P less than .000001) and 2015 (2013 vs 2015, P less than .00001). The detection rates in 2014 and 2015 were similar (P equal to .59), according to Dr. Tanz.
The new era of molecular testing circumvents what is known as the spectrum effect, in which culture-based tests are more often positive in patients with symptoms that are consistent with the infection, he said. In contrast, molecular tests can increase the identification of the target bacterium, here GAS, in patients who have sore throat caused by a viral infection.
Preliminary results presented by Dr. Tanz indicated a significantly greater detection of GAS in children not displaying symptoms of infection. In decades past, these children would not have been treated.
“The increase in positive tests for group A strep is likely associated with increased antibiotic prescribing. This may or may not represent a benefit to patients, as the additional identified patients may not have an illness actually attributable to group A strep,” said Dr. Tanz.
“Our findings support rigorous selectivity in choosing which patients to test, specifically excluding those with overt viral symptoms, as recommended in the guidelines from the [Infectious Diseases Society of America], [American Academy of Pediatrics], and other groups,” he said, adding that clinician guidance on the use of molecular diagnostic tests for pharyngitis caused by group A strep is a prudent step.
Features suggestive of GAS may include sudden onset of sore throat, age 5-15 years, fever, headache, nausea, vomiting, and abdominal pain, tonsillopharyngeal inflammation and patchy tonsillopharyngeal exudates, palatal petechiae, tender nodes, and scarlatiniform rash. Viral pharyngitis features include conjunctivitis, coryza, cough, diarrhea, discrete ulcerative stomatitis, viral exanthema, and hoarseness, according to the 2012 Infectious Diseases Society of American guidelines (Clin Infect Dis. 2012. doi: 10.1093/cid/cis629).
For most people, a sore throat is more of a temporary inconvenience rather than a looming health threat, but GAS easily spreads from person to person and can lead to the more serious condition of acute rheumatic fever, Dr. Tanz said. Hence the concern with diagnosing the cause of sore throat and, when the cause is bacterial, alleviating the infection using antibiotics.
The study was conducted at Ann & Robert H. Lurie Children’s Hospital of Chicago and was not funded. Dr. Tanz reported having received support from Meridian Bioscience, manufacturer of the Illumigene Group A Streptococcus assay. Meridian Bioscience did not support this study.
Key clinical point: The increased molecular-based detection of group A streptococci could led to antibiotic overuse, with prescriptions for patients who do not have bacterial infections.
Major finding: In the most recent year of culture-based testing at Lurie Children’s Hospital, the detection rate of group A streptococci was 9.6%; detection rates were 17.0% and 16.1% in the next 2 years when molecular-based analysis was implemented.
Data source: Quality assessment study involving a retrospective review of hospital electronic medical records.
Disclosures: The study was conducted at Ann & Robert H. Lurie Children’s Hospital of Chicago and was not funded. Dr. Tanz reported having received support from Meridian Bioscience, manufacturer of the Illumigene Group A Streptococcus assay. Meridian Bioscience did not support this study.
Children exposed to violence show accelerated cellular aging
SAN FRANCISCO – Children exposed to high levels of urban violence demonstrate accelerated cellular aging beyond their chronologic years, Vasiliki Michopoulos, PhD, reported at the annual conference of the Anxiety and Depression Association of America.
This fast-running cellular biologic clock is not a good thing. Neither is their blunted heart rate variability in response to stress, an indicator of autonomic dysfunction that constitutes a cardiovascular risk factor, she added.
Accelerated cellular aging as measured by DNA methylation in blood or saliva samples has become a red hot research area. Investigators have shown that a person’s DNA methylation age, also known as epigenetic age, predicts all-cause mortality risk in later life. In adults, accelerated cellular aging as reflected in a 5-year discrepancy between DNA methylation age and chronologic age is predictive of an adjusted 16% increased mortality risk independent of social class, education level, lifestyle factors, and chronic diseases, including diabetes and cardiovascular disease (Genome Biol. 2015 Jan 30;16:25).
Lifetime exposure to stress has been convincingly shown to accelerate epigenetic aging, as reflected by DNA methylation level. But, prior to Dr. Michopoulos’s study, it wasn’t known if exposure to violence during childhood influences epigenetic aging or if perhaps only later-life trauma is relevant.
To address this question, she and her coinvestigators recruited 101 African American children aged 6-11 years and their mothers. Of note, medical attention wasn’t being sought for the children. Rather, their mothers were approached regarding study participation while attending primary care clinics at Atlanta’s Grady Memorial Hospital. Children were not eligible to participate if they had been diagnosed with autism spectrum disorder, bipolar disorder, cognitive impairment, or a psychotic disorder.
The children had been exposed to a lot of violence, both witnessed and directly experienced, as reflected in their mean total score of 18.9 on the Violence Exposure Scale for Children-Revised (VEX-R). More than 80% of the children had witnessed an assault and 30% a murder. Stabbings, shootings, drug trafficking, and arrests were other common exposures.
One-quarter of the children showed accelerated cellular aging. They had experienced twice as much violence exposure as reflected in their VEX-R scores, compared with children whose epigenetic and chronologic ages were the same.
The children with accelerated cellular aging also demonstrated decreased heart rate variability in response to a standardized stressor, which involved a startle experience in a darkened room. Their heart rate in the stressor situation shot up on average by 17 bpm less than the children whose cellular age as measured by DNA methylation matched their chronologic age.
“Our data suggest that DNA methylation may serve as a biomarker by which to identify at-risk individuals who may benefit from interventions that decrease risk for cardiometabolic disorders in adulthood,” Dr. Michopoulos said. “It’ll be really interesting to see, as these kids grow up and develop, whether their phenotype stays static, reverses, or changes completely.”
Dr. Michopoulos reported having no financial conflicts regarding the study, conducted as part of the Grady Trauma Project (www.gradytraumaproject.com) with funding from the National Institute of Mental Health and Emory University and Grady Memorial Hospital, both in Atlanta.
SAN FRANCISCO – Children exposed to high levels of urban violence demonstrate accelerated cellular aging beyond their chronologic years, Vasiliki Michopoulos, PhD, reported at the annual conference of the Anxiety and Depression Association of America.
This fast-running cellular biologic clock is not a good thing. Neither is their blunted heart rate variability in response to stress, an indicator of autonomic dysfunction that constitutes a cardiovascular risk factor, she added.
Accelerated cellular aging as measured by DNA methylation in blood or saliva samples has become a red hot research area. Investigators have shown that a person’s DNA methylation age, also known as epigenetic age, predicts all-cause mortality risk in later life. In adults, accelerated cellular aging as reflected in a 5-year discrepancy between DNA methylation age and chronologic age is predictive of an adjusted 16% increased mortality risk independent of social class, education level, lifestyle factors, and chronic diseases, including diabetes and cardiovascular disease (Genome Biol. 2015 Jan 30;16:25).
Lifetime exposure to stress has been convincingly shown to accelerate epigenetic aging, as reflected by DNA methylation level. But, prior to Dr. Michopoulos’s study, it wasn’t known if exposure to violence during childhood influences epigenetic aging or if perhaps only later-life trauma is relevant.
To address this question, she and her coinvestigators recruited 101 African American children aged 6-11 years and their mothers. Of note, medical attention wasn’t being sought for the children. Rather, their mothers were approached regarding study participation while attending primary care clinics at Atlanta’s Grady Memorial Hospital. Children were not eligible to participate if they had been diagnosed with autism spectrum disorder, bipolar disorder, cognitive impairment, or a psychotic disorder.
The children had been exposed to a lot of violence, both witnessed and directly experienced, as reflected in their mean total score of 18.9 on the Violence Exposure Scale for Children-Revised (VEX-R). More than 80% of the children had witnessed an assault and 30% a murder. Stabbings, shootings, drug trafficking, and arrests were other common exposures.
One-quarter of the children showed accelerated cellular aging. They had experienced twice as much violence exposure as reflected in their VEX-R scores, compared with children whose epigenetic and chronologic ages were the same.
The children with accelerated cellular aging also demonstrated decreased heart rate variability in response to a standardized stressor, which involved a startle experience in a darkened room. Their heart rate in the stressor situation shot up on average by 17 bpm less than the children whose cellular age as measured by DNA methylation matched their chronologic age.
“Our data suggest that DNA methylation may serve as a biomarker by which to identify at-risk individuals who may benefit from interventions that decrease risk for cardiometabolic disorders in adulthood,” Dr. Michopoulos said. “It’ll be really interesting to see, as these kids grow up and develop, whether their phenotype stays static, reverses, or changes completely.”
Dr. Michopoulos reported having no financial conflicts regarding the study, conducted as part of the Grady Trauma Project (www.gradytraumaproject.com) with funding from the National Institute of Mental Health and Emory University and Grady Memorial Hospital, both in Atlanta.
SAN FRANCISCO – Children exposed to high levels of urban violence demonstrate accelerated cellular aging beyond their chronologic years, Vasiliki Michopoulos, PhD, reported at the annual conference of the Anxiety and Depression Association of America.
This fast-running cellular biologic clock is not a good thing. Neither is their blunted heart rate variability in response to stress, an indicator of autonomic dysfunction that constitutes a cardiovascular risk factor, she added.
Accelerated cellular aging as measured by DNA methylation in blood or saliva samples has become a red hot research area. Investigators have shown that a person’s DNA methylation age, also known as epigenetic age, predicts all-cause mortality risk in later life. In adults, accelerated cellular aging as reflected in a 5-year discrepancy between DNA methylation age and chronologic age is predictive of an adjusted 16% increased mortality risk independent of social class, education level, lifestyle factors, and chronic diseases, including diabetes and cardiovascular disease (Genome Biol. 2015 Jan 30;16:25).
Lifetime exposure to stress has been convincingly shown to accelerate epigenetic aging, as reflected by DNA methylation level. But, prior to Dr. Michopoulos’s study, it wasn’t known if exposure to violence during childhood influences epigenetic aging or if perhaps only later-life trauma is relevant.
To address this question, she and her coinvestigators recruited 101 African American children aged 6-11 years and their mothers. Of note, medical attention wasn’t being sought for the children. Rather, their mothers were approached regarding study participation while attending primary care clinics at Atlanta’s Grady Memorial Hospital. Children were not eligible to participate if they had been diagnosed with autism spectrum disorder, bipolar disorder, cognitive impairment, or a psychotic disorder.
The children had been exposed to a lot of violence, both witnessed and directly experienced, as reflected in their mean total score of 18.9 on the Violence Exposure Scale for Children-Revised (VEX-R). More than 80% of the children had witnessed an assault and 30% a murder. Stabbings, shootings, drug trafficking, and arrests were other common exposures.
One-quarter of the children showed accelerated cellular aging. They had experienced twice as much violence exposure as reflected in their VEX-R scores, compared with children whose epigenetic and chronologic ages were the same.
The children with accelerated cellular aging also demonstrated decreased heart rate variability in response to a standardized stressor, which involved a startle experience in a darkened room. Their heart rate in the stressor situation shot up on average by 17 bpm less than the children whose cellular age as measured by DNA methylation matched their chronologic age.
“Our data suggest that DNA methylation may serve as a biomarker by which to identify at-risk individuals who may benefit from interventions that decrease risk for cardiometabolic disorders in adulthood,” Dr. Michopoulos said. “It’ll be really interesting to see, as these kids grow up and develop, whether their phenotype stays static, reverses, or changes completely.”
Dr. Michopoulos reported having no financial conflicts regarding the study, conducted as part of the Grady Trauma Project (www.gradytraumaproject.com) with funding from the National Institute of Mental Health and Emory University and Grady Memorial Hospital, both in Atlanta.
AT THE ANXIETY AND DEPRESSION CONFERENCE 2017
Key clinical point:
Major finding: Children who demonstrated advanced cellular aging based on DNA methylation levels had experienced twice as much exposure to violence as those whose epigenetic and chronologic ages matched.
Data source: This cross-sectional study included 101 urban African American children aged 6-11 years.
Disclosures: The presenter reported having no financial conflicts regarding the study, which was funded by the National Institute of Mental Health and Emory University and Grady Memorial Hospital, both in Atlanta.
Safe, effective backup for U.S. MMR vaccine exists
Antibodies against measles, mumps, and rubella persisted for up to 2 years after vaccination of children 12-15 months with the MMR vaccine approved in the United States and a similar one approved in Europe, both of which are manufactured without human serum albumin, Andrea A. Berry, MD, at the University of Maryland, Baltimore, and her associates said.
In 752 children aged a mean 12 months who received either the United States MMR vaccine and the European one, seropositivity for measles, mumps, and rubella persisted for up to 2 years with both vaccines. Both vaccines also were well tolerated.
Because there is only one MMR vaccine licensed in the United States, interruption to this single supply line could present a public health risk, Dr. Berry and her associates said. As both the vaccines used in this study do not contain human serum albumin, the theoretical risk of microbial contamination is reduced, compared with previous formulations of MMR.
Read more at Human Vaccines Immunotherapeutics. (2017. doi: 10.1080/21645515.2017.1309486).
Antibodies against measles, mumps, and rubella persisted for up to 2 years after vaccination of children 12-15 months with the MMR vaccine approved in the United States and a similar one approved in Europe, both of which are manufactured without human serum albumin, Andrea A. Berry, MD, at the University of Maryland, Baltimore, and her associates said.
In 752 children aged a mean 12 months who received either the United States MMR vaccine and the European one, seropositivity for measles, mumps, and rubella persisted for up to 2 years with both vaccines. Both vaccines also were well tolerated.
Because there is only one MMR vaccine licensed in the United States, interruption to this single supply line could present a public health risk, Dr. Berry and her associates said. As both the vaccines used in this study do not contain human serum albumin, the theoretical risk of microbial contamination is reduced, compared with previous formulations of MMR.
Read more at Human Vaccines Immunotherapeutics. (2017. doi: 10.1080/21645515.2017.1309486).
Antibodies against measles, mumps, and rubella persisted for up to 2 years after vaccination of children 12-15 months with the MMR vaccine approved in the United States and a similar one approved in Europe, both of which are manufactured without human serum albumin, Andrea A. Berry, MD, at the University of Maryland, Baltimore, and her associates said.
In 752 children aged a mean 12 months who received either the United States MMR vaccine and the European one, seropositivity for measles, mumps, and rubella persisted for up to 2 years with both vaccines. Both vaccines also were well tolerated.
Because there is only one MMR vaccine licensed in the United States, interruption to this single supply line could present a public health risk, Dr. Berry and her associates said. As both the vaccines used in this study do not contain human serum albumin, the theoretical risk of microbial contamination is reduced, compared with previous formulations of MMR.
Read more at Human Vaccines Immunotherapeutics. (2017. doi: 10.1080/21645515.2017.1309486).
FROM HUMAN VACCINES & IMMUNOTHERAPEUTICS
Time to therapy for gram-positive bacteremia reduced from 60 hours to 4 hours
SAN FRANCISCO – Implementation of sample testing using a molecular approach, combined with coordinated and multidisciplinary notification of clinicians, has reduced the time to deliver adequate antibiotic therapy for bacteremia caused by gram-positive cocci including methicillin-resistant Staphylococcus aureus (MRSA) from 60 hours to 4 hours.
“We observed a significant decrease in the time to adequate antibiotics, significant decrease in time to first negative blood culture, and decreased variation in both measures,” Michael Tchou, MD, of the division of hospital medicine at Cincinnati Children’s Hospital Medical Center (CCHMC), reported at the Pediatric Academic Societies meeting.
Speeding up the time to delivery of adequate antibiotics is a must, Dr. Tchou emphasized.
CCHMC initiated the use of a multiplex polymerase chain reaction (PCR)–based identification protocol in mid-2013. Multiplex PCR targets specific regions of genetic material. In the protocol, empiric antibiotics are administered. At the same time, multiplex PCR is done. Blood culture and subsequent Gram staining of the bacteria in the colonies that grow also are done. PCR-based species identification and determination of probable antibiotic resistance, which takes about 3 hours, can be used to shift antibiotic therapy to adequate therapy, which is defined as the necessary antimicrobial therapy, even if it is still too broad. The growth-based results available the next day help fine-tune the therapy.
The use of multiplex PCR speeds the time to an “actionable result” – the time to recognize that the empiric antibiotic therapy is not the best, Dr. Tchou said.
At CCHMC, an actionable result is obtained for about 1 of every 40 cases of bloodstream infection determined to be caused by gram-positive cocci. The delay in switching to adequate antibiotic coverage used to average 60 hours.
In an effort to do better, Dr. Tchou and colleagues set a goal of reducing the time to adequate antibiotic therapy for gram-positive bacteremia from 60 to 12 hours within 6 months.
The effort necessitated the coordinated involvement of a multidisciplinary team, with a rapid system of clinician notification, and the real-time software-based monitoring of results. In the system, an actionable result triggers a text message to the on-call antibiotic stewardship contact, who in turn notifies the primary care team.
The multidisciplinary system was rolled out first for MRSA. The effort was even more successful than they hoped for. Delivery of appropriate antibiotics for MRSA infections dropped from about 60 hours to 13 hours within a few months, with a further decrease to 4 hours within another few months. Roll out of the initiative to all gram-positive cocci including coagulase-negative staphylococci, Streptococcus pyogenes, Enterococcus faecalis, and E. faecium similarly achieved the 4-hour target within months.
And preliminary results not presented by Dr. Tchou indicate an earlier resolution of bacteremia.
Next steps include modifying the decision support software to allow direct paging of providers instead of using text messages, expansion of the antibiotic coverage, and achieving similar improved treatment time for gram-negative bloodstream infections.
The study was sponsored by Cincinnati Children’s Hospital and was not funded. Dr. Tchou reported having no relevant financial disclosures.
SAN FRANCISCO – Implementation of sample testing using a molecular approach, combined with coordinated and multidisciplinary notification of clinicians, has reduced the time to deliver adequate antibiotic therapy for bacteremia caused by gram-positive cocci including methicillin-resistant Staphylococcus aureus (MRSA) from 60 hours to 4 hours.
“We observed a significant decrease in the time to adequate antibiotics, significant decrease in time to first negative blood culture, and decreased variation in both measures,” Michael Tchou, MD, of the division of hospital medicine at Cincinnati Children’s Hospital Medical Center (CCHMC), reported at the Pediatric Academic Societies meeting.
Speeding up the time to delivery of adequate antibiotics is a must, Dr. Tchou emphasized.
CCHMC initiated the use of a multiplex polymerase chain reaction (PCR)–based identification protocol in mid-2013. Multiplex PCR targets specific regions of genetic material. In the protocol, empiric antibiotics are administered. At the same time, multiplex PCR is done. Blood culture and subsequent Gram staining of the bacteria in the colonies that grow also are done. PCR-based species identification and determination of probable antibiotic resistance, which takes about 3 hours, can be used to shift antibiotic therapy to adequate therapy, which is defined as the necessary antimicrobial therapy, even if it is still too broad. The growth-based results available the next day help fine-tune the therapy.
The use of multiplex PCR speeds the time to an “actionable result” – the time to recognize that the empiric antibiotic therapy is not the best, Dr. Tchou said.
At CCHMC, an actionable result is obtained for about 1 of every 40 cases of bloodstream infection determined to be caused by gram-positive cocci. The delay in switching to adequate antibiotic coverage used to average 60 hours.
In an effort to do better, Dr. Tchou and colleagues set a goal of reducing the time to adequate antibiotic therapy for gram-positive bacteremia from 60 to 12 hours within 6 months.
The effort necessitated the coordinated involvement of a multidisciplinary team, with a rapid system of clinician notification, and the real-time software-based monitoring of results. In the system, an actionable result triggers a text message to the on-call antibiotic stewardship contact, who in turn notifies the primary care team.
The multidisciplinary system was rolled out first for MRSA. The effort was even more successful than they hoped for. Delivery of appropriate antibiotics for MRSA infections dropped from about 60 hours to 13 hours within a few months, with a further decrease to 4 hours within another few months. Roll out of the initiative to all gram-positive cocci including coagulase-negative staphylococci, Streptococcus pyogenes, Enterococcus faecalis, and E. faecium similarly achieved the 4-hour target within months.
And preliminary results not presented by Dr. Tchou indicate an earlier resolution of bacteremia.
Next steps include modifying the decision support software to allow direct paging of providers instead of using text messages, expansion of the antibiotic coverage, and achieving similar improved treatment time for gram-negative bloodstream infections.
The study was sponsored by Cincinnati Children’s Hospital and was not funded. Dr. Tchou reported having no relevant financial disclosures.
SAN FRANCISCO – Implementation of sample testing using a molecular approach, combined with coordinated and multidisciplinary notification of clinicians, has reduced the time to deliver adequate antibiotic therapy for bacteremia caused by gram-positive cocci including methicillin-resistant Staphylococcus aureus (MRSA) from 60 hours to 4 hours.
“We observed a significant decrease in the time to adequate antibiotics, significant decrease in time to first negative blood culture, and decreased variation in both measures,” Michael Tchou, MD, of the division of hospital medicine at Cincinnati Children’s Hospital Medical Center (CCHMC), reported at the Pediatric Academic Societies meeting.
Speeding up the time to delivery of adequate antibiotics is a must, Dr. Tchou emphasized.
CCHMC initiated the use of a multiplex polymerase chain reaction (PCR)–based identification protocol in mid-2013. Multiplex PCR targets specific regions of genetic material. In the protocol, empiric antibiotics are administered. At the same time, multiplex PCR is done. Blood culture and subsequent Gram staining of the bacteria in the colonies that grow also are done. PCR-based species identification and determination of probable antibiotic resistance, which takes about 3 hours, can be used to shift antibiotic therapy to adequate therapy, which is defined as the necessary antimicrobial therapy, even if it is still too broad. The growth-based results available the next day help fine-tune the therapy.
The use of multiplex PCR speeds the time to an “actionable result” – the time to recognize that the empiric antibiotic therapy is not the best, Dr. Tchou said.
At CCHMC, an actionable result is obtained for about 1 of every 40 cases of bloodstream infection determined to be caused by gram-positive cocci. The delay in switching to adequate antibiotic coverage used to average 60 hours.
In an effort to do better, Dr. Tchou and colleagues set a goal of reducing the time to adequate antibiotic therapy for gram-positive bacteremia from 60 to 12 hours within 6 months.
The effort necessitated the coordinated involvement of a multidisciplinary team, with a rapid system of clinician notification, and the real-time software-based monitoring of results. In the system, an actionable result triggers a text message to the on-call antibiotic stewardship contact, who in turn notifies the primary care team.
The multidisciplinary system was rolled out first for MRSA. The effort was even more successful than they hoped for. Delivery of appropriate antibiotics for MRSA infections dropped from about 60 hours to 13 hours within a few months, with a further decrease to 4 hours within another few months. Roll out of the initiative to all gram-positive cocci including coagulase-negative staphylococci, Streptococcus pyogenes, Enterococcus faecalis, and E. faecium similarly achieved the 4-hour target within months.
And preliminary results not presented by Dr. Tchou indicate an earlier resolution of bacteremia.
Next steps include modifying the decision support software to allow direct paging of providers instead of using text messages, expansion of the antibiotic coverage, and achieving similar improved treatment time for gram-negative bloodstream infections.
The study was sponsored by Cincinnati Children’s Hospital and was not funded. Dr. Tchou reported having no relevant financial disclosures.
AT PAS 2017
Key clinical point: Multiplex PCR and a revamped system of notification reduced the time to deliver adequate antibiotic therapy for bacteremia caused by gram-positive cocci from 60 hours to 4 hours within 6 months of implementation.
Major finding: and other gram-positive cocci-related infections.
Data source: A retrospective review of hospital records including patient data prior to and following implementation of multiplex PCR testing at one hospital.
Disclosures: The study was sponsored by Cincinnati Children’s Hospital and was not funded. Dr. Tchou reported having no relevant financial disclosures.
Isothiazolinone allergy frequent and underdiagnosed in children
Sensitization to the isothiazolinones MCI (methylchloroisothiazolinone) and MI (methylisothiazolinone), which are used as preservatives in a wide variety of personal and household products, is both frequent and underdiagnosed in U.S. children, according to a report published in Pediatric Dermatology.
These agents are compatible with surfactants and emulsifiers, and because they maintain biocidal activity across a broad range of pH levels they are frequently used as preservatives in products such as wet wipes; shampoos and hair conditioners; soaps, cleansers, and disinfectants; and laundry products. However, they are known to cause contact dermatitis very frequently, and are among the top five contact allergens identified in infants’ patch tests.
A recent survey showed that among 152 pediatric skin care products available at major retail stores, 20% contained MI. These were specifically targeted to infants and children, advertised as being “hypoallergenic,” “natural,” good for “sensitive” skin, and containing “gentle ingredients,” said Alina Goldenberg, MD, of the department of dermatology at the University of California, San Diego, and her associates.
During the past 10 years, only 35 U.S. cases of a positive patch-test reaction to MCI and/or MI have been reported in the literature. To get a more accurate estimate of the true prevalence of pediatric sensitization to MCI and MI, the investigators analyzed information in a database of patch-test results, the Provider Contact Dermatitis Registry. They focused on 1,056 patch tests performed during a 1-year period.
They found 37 positive reactions to combined MCI/MI and another 39 reactions that were negative to combined MCI/MI but positive to MI alone. This shows how important it is to test for sensitization to both formulations separately, Dr. Goldenberg and her associates noted (Pediatr Dermatol. 2017 Mar;34[2]:138-43).
In stark contrast to the reported 35 cases across the entire country during a 10-year period, the investigators found 76 cases (1%) in 1,056 patch tests during a 1-year period.
When test results for MCI/MI and MI alone were compared with those for all other allergens, children sensitized to the isothiazolinones showed marked differences: They were significantly younger, and the location of their dermatitis was more likely to involve the groin and buttocks. This probably is due to the increased use of wet wipes containing MCI and MI being used to clean up urinary and fecal accidents in young children, the researchers said.
The Society for Pediatric Dermatology supported the work. Dr. Goldenberg reported having no relevant financial disclosures; an associate reported serving as a consultant for Johnson & Johnson.
Sensitization to the isothiazolinones MCI (methylchloroisothiazolinone) and MI (methylisothiazolinone), which are used as preservatives in a wide variety of personal and household products, is both frequent and underdiagnosed in U.S. children, according to a report published in Pediatric Dermatology.
These agents are compatible with surfactants and emulsifiers, and because they maintain biocidal activity across a broad range of pH levels they are frequently used as preservatives in products such as wet wipes; shampoos and hair conditioners; soaps, cleansers, and disinfectants; and laundry products. However, they are known to cause contact dermatitis very frequently, and are among the top five contact allergens identified in infants’ patch tests.
A recent survey showed that among 152 pediatric skin care products available at major retail stores, 20% contained MI. These were specifically targeted to infants and children, advertised as being “hypoallergenic,” “natural,” good for “sensitive” skin, and containing “gentle ingredients,” said Alina Goldenberg, MD, of the department of dermatology at the University of California, San Diego, and her associates.
During the past 10 years, only 35 U.S. cases of a positive patch-test reaction to MCI and/or MI have been reported in the literature. To get a more accurate estimate of the true prevalence of pediatric sensitization to MCI and MI, the investigators analyzed information in a database of patch-test results, the Provider Contact Dermatitis Registry. They focused on 1,056 patch tests performed during a 1-year period.
They found 37 positive reactions to combined MCI/MI and another 39 reactions that were negative to combined MCI/MI but positive to MI alone. This shows how important it is to test for sensitization to both formulations separately, Dr. Goldenberg and her associates noted (Pediatr Dermatol. 2017 Mar;34[2]:138-43).
In stark contrast to the reported 35 cases across the entire country during a 10-year period, the investigators found 76 cases (1%) in 1,056 patch tests during a 1-year period.
When test results for MCI/MI and MI alone were compared with those for all other allergens, children sensitized to the isothiazolinones showed marked differences: They were significantly younger, and the location of their dermatitis was more likely to involve the groin and buttocks. This probably is due to the increased use of wet wipes containing MCI and MI being used to clean up urinary and fecal accidents in young children, the researchers said.
The Society for Pediatric Dermatology supported the work. Dr. Goldenberg reported having no relevant financial disclosures; an associate reported serving as a consultant for Johnson & Johnson.
Sensitization to the isothiazolinones MCI (methylchloroisothiazolinone) and MI (methylisothiazolinone), which are used as preservatives in a wide variety of personal and household products, is both frequent and underdiagnosed in U.S. children, according to a report published in Pediatric Dermatology.
These agents are compatible with surfactants and emulsifiers, and because they maintain biocidal activity across a broad range of pH levels they are frequently used as preservatives in products such as wet wipes; shampoos and hair conditioners; soaps, cleansers, and disinfectants; and laundry products. However, they are known to cause contact dermatitis very frequently, and are among the top five contact allergens identified in infants’ patch tests.
A recent survey showed that among 152 pediatric skin care products available at major retail stores, 20% contained MI. These were specifically targeted to infants and children, advertised as being “hypoallergenic,” “natural,” good for “sensitive” skin, and containing “gentle ingredients,” said Alina Goldenberg, MD, of the department of dermatology at the University of California, San Diego, and her associates.
During the past 10 years, only 35 U.S. cases of a positive patch-test reaction to MCI and/or MI have been reported in the literature. To get a more accurate estimate of the true prevalence of pediatric sensitization to MCI and MI, the investigators analyzed information in a database of patch-test results, the Provider Contact Dermatitis Registry. They focused on 1,056 patch tests performed during a 1-year period.
They found 37 positive reactions to combined MCI/MI and another 39 reactions that were negative to combined MCI/MI but positive to MI alone. This shows how important it is to test for sensitization to both formulations separately, Dr. Goldenberg and her associates noted (Pediatr Dermatol. 2017 Mar;34[2]:138-43).
In stark contrast to the reported 35 cases across the entire country during a 10-year period, the investigators found 76 cases (1%) in 1,056 patch tests during a 1-year period.
When test results for MCI/MI and MI alone were compared with those for all other allergens, children sensitized to the isothiazolinones showed marked differences: They were significantly younger, and the location of their dermatitis was more likely to involve the groin and buttocks. This probably is due to the increased use of wet wipes containing MCI and MI being used to clean up urinary and fecal accidents in young children, the researchers said.
The Society for Pediatric Dermatology supported the work. Dr. Goldenberg reported having no relevant financial disclosures; an associate reported serving as a consultant for Johnson & Johnson.
FROM PEDIATRIC DERMATOLOGY
Key clinical point:
Major finding: There were 37 positive patch-test reactions to combined MCI/MI and another 39 reactions that were negative to combined MCI/MI but positive to MI alone.
Data source: An analysis of 1,056 patch-test results recorded in a database by clinicians during a 1-year period.
Disclosures: The Society for Pediatric Dermatology supported the work. Dr. Goldenberg reported having no relevant financial disclosures; an associate reported serving as a consultant for Johnson & Johnson.
Non-cow’s milk associated with lower childhood height
SAN FRANCISCO – Consumption of non-cow’s milk in early childhood is associated with decreased height, compared with consumption of cow’s milk by children in the same stage of life, a study has shown. The results call into question perceived health benefits of the consumption of non-cow’s milk in childhood.
“These findings are important for health care workers and parents in terms of optimal growth of children and the kind of milk needed to achieve that,” presenter Marie-Elssa Morency explained at the meeting of the Pediatric Academic Societies. Ms. Morency is a master’s student in the department of nutritional sciences at the University of Toronto.
Whether cow’s milk is a better source than non-cow’s milk of nutritional and caloric energy to a growing body has not been studied with rigor. Perceived health benefits of non-cow’s milk have led some parents to substitute cow’s milk with other types of milk for their children, Ms. Morency said.
To gain some clarity, the researchers looked at data from the TARGetKids! longitudinal cohort of children. The cohort is being followed into adolescence to link early life exposures to various physiological and developmental health problems. The present study looked at more than 5,000 healthy children aged 24-72 months. Any conditions that could affect growth were grounds for exclusion.
The primary exposure was the daily consumption of cow’s milk in 4,632 children or non-cow’s milk in 643 children. The typical number of 250-mL glasses of milk consumed per day was gleaned by a questionnaire completed by the parents. The primary outcome was height-for-age z score.
The two groups were similar at baseline in age, sex (slightly more than half were male), body mass index, and maternal height. Those who predominantly consumed cow’s milk averaged 2 cups per day. Some also consumed non-cow’s milk (about one glass per day). Those in the non-cow’s milk group consumed on average 1.4 cups per day, with cow’s milk consumption being rare.
The overall z-score was 0.1 (95% confidence interval [CI], –0.6 to 0.8). The groups differed in z-score, with a score of 0.2 (95% CI, –0.6 to 0.8) in the cow’s milk group and –0.04 (95% CI, –0.8 to 0.7) in the non-cow’s milk group. The resulting shorter height in those consuming non-cow’s milk was 0.42 cm (95% CI, –0.61 to –0.19) in a univariate analysis (P less than .001). A multivariate analysis that adjusted for age, sex, maternal ethnicity, maternal height, z-score, and neighborhood income revealed a significant difference in the same group of 0.31 cm (95% CI, –0.50 to –0.11; P less than .001).
The reduced consumption of cow’s milk in the non-cow’s milk group was identified as a partial mediator of the association between non-cow’s milk consumption and height. Putting the results into context, Ms. Morency explained that a 3-year-old child typically drinking 3 cups of non-cow’s milk each day (about twice the average in this study) would be 1.5 cm shorter than a similar child drinking the same amount of cow’s milk each day.
The literature shows that height children achieve during childhood is an important benchmark of growth and development, adequate nutrition, and pending obesity. Shorter-than average children can often be shorter than average in height as adults, which has been linked with increased risk of type 2 diabetes, gestational diabetes, coronary heart disease, and hypertension.
Diet influences height: Reduced calories and nutrients in an inadequate diet hinder growth, Ms. Morency noted. Cow’s milk delivers more protein, fat, vitamins, minerals, and calories than do non-cow’s milk formulations, such as almond milk and soy milk, she said.
“While non-cow’s milk consumption in childhood may have other health benefits, increased height does not appear to be one of them,” said Ms. Morency.
Study strengths include the relatively large sample size, statistical rigor, and consistent findings with prior studies. Limitations include the cross-sectional design that rules out any conclusions about direct cause, and the use of questionnaire data, which inherently comes with problems of report and recall bias.
A causal connection awaits randomized controlled trials.
The University of Toronto sponsored the study, which was funded by the Canadian Institutes for Health Research. Ms. Morency reported having no financial disclosures.
SAN FRANCISCO – Consumption of non-cow’s milk in early childhood is associated with decreased height, compared with consumption of cow’s milk by children in the same stage of life, a study has shown. The results call into question perceived health benefits of the consumption of non-cow’s milk in childhood.
“These findings are important for health care workers and parents in terms of optimal growth of children and the kind of milk needed to achieve that,” presenter Marie-Elssa Morency explained at the meeting of the Pediatric Academic Societies. Ms. Morency is a master’s student in the department of nutritional sciences at the University of Toronto.
Whether cow’s milk is a better source than non-cow’s milk of nutritional and caloric energy to a growing body has not been studied with rigor. Perceived health benefits of non-cow’s milk have led some parents to substitute cow’s milk with other types of milk for their children, Ms. Morency said.
To gain some clarity, the researchers looked at data from the TARGetKids! longitudinal cohort of children. The cohort is being followed into adolescence to link early life exposures to various physiological and developmental health problems. The present study looked at more than 5,000 healthy children aged 24-72 months. Any conditions that could affect growth were grounds for exclusion.
The primary exposure was the daily consumption of cow’s milk in 4,632 children or non-cow’s milk in 643 children. The typical number of 250-mL glasses of milk consumed per day was gleaned by a questionnaire completed by the parents. The primary outcome was height-for-age z score.
The two groups were similar at baseline in age, sex (slightly more than half were male), body mass index, and maternal height. Those who predominantly consumed cow’s milk averaged 2 cups per day. Some also consumed non-cow’s milk (about one glass per day). Those in the non-cow’s milk group consumed on average 1.4 cups per day, with cow’s milk consumption being rare.
The overall z-score was 0.1 (95% confidence interval [CI], –0.6 to 0.8). The groups differed in z-score, with a score of 0.2 (95% CI, –0.6 to 0.8) in the cow’s milk group and –0.04 (95% CI, –0.8 to 0.7) in the non-cow’s milk group. The resulting shorter height in those consuming non-cow’s milk was 0.42 cm (95% CI, –0.61 to –0.19) in a univariate analysis (P less than .001). A multivariate analysis that adjusted for age, sex, maternal ethnicity, maternal height, z-score, and neighborhood income revealed a significant difference in the same group of 0.31 cm (95% CI, –0.50 to –0.11; P less than .001).
The reduced consumption of cow’s milk in the non-cow’s milk group was identified as a partial mediator of the association between non-cow’s milk consumption and height. Putting the results into context, Ms. Morency explained that a 3-year-old child typically drinking 3 cups of non-cow’s milk each day (about twice the average in this study) would be 1.5 cm shorter than a similar child drinking the same amount of cow’s milk each day.
The literature shows that height children achieve during childhood is an important benchmark of growth and development, adequate nutrition, and pending obesity. Shorter-than average children can often be shorter than average in height as adults, which has been linked with increased risk of type 2 diabetes, gestational diabetes, coronary heart disease, and hypertension.
Diet influences height: Reduced calories and nutrients in an inadequate diet hinder growth, Ms. Morency noted. Cow’s milk delivers more protein, fat, vitamins, minerals, and calories than do non-cow’s milk formulations, such as almond milk and soy milk, she said.
“While non-cow’s milk consumption in childhood may have other health benefits, increased height does not appear to be one of them,” said Ms. Morency.
Study strengths include the relatively large sample size, statistical rigor, and consistent findings with prior studies. Limitations include the cross-sectional design that rules out any conclusions about direct cause, and the use of questionnaire data, which inherently comes with problems of report and recall bias.
A causal connection awaits randomized controlled trials.
The University of Toronto sponsored the study, which was funded by the Canadian Institutes for Health Research. Ms. Morency reported having no financial disclosures.
SAN FRANCISCO – Consumption of non-cow’s milk in early childhood is associated with decreased height, compared with consumption of cow’s milk by children in the same stage of life, a study has shown. The results call into question perceived health benefits of the consumption of non-cow’s milk in childhood.
“These findings are important for health care workers and parents in terms of optimal growth of children and the kind of milk needed to achieve that,” presenter Marie-Elssa Morency explained at the meeting of the Pediatric Academic Societies. Ms. Morency is a master’s student in the department of nutritional sciences at the University of Toronto.
Whether cow’s milk is a better source than non-cow’s milk of nutritional and caloric energy to a growing body has not been studied with rigor. Perceived health benefits of non-cow’s milk have led some parents to substitute cow’s milk with other types of milk for their children, Ms. Morency said.
To gain some clarity, the researchers looked at data from the TARGetKids! longitudinal cohort of children. The cohort is being followed into adolescence to link early life exposures to various physiological and developmental health problems. The present study looked at more than 5,000 healthy children aged 24-72 months. Any conditions that could affect growth were grounds for exclusion.
The primary exposure was the daily consumption of cow’s milk in 4,632 children or non-cow’s milk in 643 children. The typical number of 250-mL glasses of milk consumed per day was gleaned by a questionnaire completed by the parents. The primary outcome was height-for-age z score.
The two groups were similar at baseline in age, sex (slightly more than half were male), body mass index, and maternal height. Those who predominantly consumed cow’s milk averaged 2 cups per day. Some also consumed non-cow’s milk (about one glass per day). Those in the non-cow’s milk group consumed on average 1.4 cups per day, with cow’s milk consumption being rare.
The overall z-score was 0.1 (95% confidence interval [CI], –0.6 to 0.8). The groups differed in z-score, with a score of 0.2 (95% CI, –0.6 to 0.8) in the cow’s milk group and –0.04 (95% CI, –0.8 to 0.7) in the non-cow’s milk group. The resulting shorter height in those consuming non-cow’s milk was 0.42 cm (95% CI, –0.61 to –0.19) in a univariate analysis (P less than .001). A multivariate analysis that adjusted for age, sex, maternal ethnicity, maternal height, z-score, and neighborhood income revealed a significant difference in the same group of 0.31 cm (95% CI, –0.50 to –0.11; P less than .001).
The reduced consumption of cow’s milk in the non-cow’s milk group was identified as a partial mediator of the association between non-cow’s milk consumption and height. Putting the results into context, Ms. Morency explained that a 3-year-old child typically drinking 3 cups of non-cow’s milk each day (about twice the average in this study) would be 1.5 cm shorter than a similar child drinking the same amount of cow’s milk each day.
The literature shows that height children achieve during childhood is an important benchmark of growth and development, adequate nutrition, and pending obesity. Shorter-than average children can often be shorter than average in height as adults, which has been linked with increased risk of type 2 diabetes, gestational diabetes, coronary heart disease, and hypertension.
Diet influences height: Reduced calories and nutrients in an inadequate diet hinder growth, Ms. Morency noted. Cow’s milk delivers more protein, fat, vitamins, minerals, and calories than do non-cow’s milk formulations, such as almond milk and soy milk, she said.
“While non-cow’s milk consumption in childhood may have other health benefits, increased height does not appear to be one of them,” said Ms. Morency.
Study strengths include the relatively large sample size, statistical rigor, and consistent findings with prior studies. Limitations include the cross-sectional design that rules out any conclusions about direct cause, and the use of questionnaire data, which inherently comes with problems of report and recall bias.
A causal connection awaits randomized controlled trials.
The University of Toronto sponsored the study, which was funded by the Canadian Institutes for Health Research. Ms. Morency reported having no financial disclosures.
Lower-dose aluminum hydroxide–adjuvanted polio vaccine noninferior to standard IPV
Aluminum hydroxide–adjuvanted vaccines with reduced doses of inactivated polio vaccine (IPV-Al) were noninferior to standard inactivated poliovirus vaccine (IPV) in a large trial in the Dominican Republic, said Luis Rivera, MD, of the Hospital Maternidad Nuestra Señora de la Altagracia, Santo Domingo, Dominican Republic, and his associates.
If these findings are replicated in phase III trials and regulatory approval follows, such vaccines could be low-cost replacements for standard IPV and oral poliovirus vaccines in low-resource countries, the study authors suggested.
In this phase II, blinded, randomized trial with three investigational IPV-Al groups and one IPV group, the vaccines were given at 6 weeks, 10 weeks, 14 weeks, and 18 weeks to 823 infants who had not previously received any polio vaccination. The three new IPV-Al vaccines all proved to be noninferior to IPV for poliovirus types 1, 2, and 3.
For 1/10 IPV-Al, the seroconversion rates for the different poliovirus types were 98.5% (type 1), 94.6% (type 2), and 99.5% (type 3), compared with 100% (type 1), 98.5% (type 2), and 100% (type 3) for IPV.
This and the results from other studies “have paved the way for further clinical investigations of IPV-Al in phase III trials,” Dr. Rivera and his associates wrote.
“The low frequency of adverse events in this phase II trial suggests that a safety evaluation is not necessarily justified,” they concluded.
The Bill & Melinda Gates Foundation funded the study. The authors had no disclosures.
Read more in the Lancet Infectious Diseases (2017 Apr 25. doi: 10.1016/S1473-3099(17)30177-9).
Aluminum hydroxide–adjuvanted vaccines with reduced doses of inactivated polio vaccine (IPV-Al) were noninferior to standard inactivated poliovirus vaccine (IPV) in a large trial in the Dominican Republic, said Luis Rivera, MD, of the Hospital Maternidad Nuestra Señora de la Altagracia, Santo Domingo, Dominican Republic, and his associates.
If these findings are replicated in phase III trials and regulatory approval follows, such vaccines could be low-cost replacements for standard IPV and oral poliovirus vaccines in low-resource countries, the study authors suggested.
In this phase II, blinded, randomized trial with three investigational IPV-Al groups and one IPV group, the vaccines were given at 6 weeks, 10 weeks, 14 weeks, and 18 weeks to 823 infants who had not previously received any polio vaccination. The three new IPV-Al vaccines all proved to be noninferior to IPV for poliovirus types 1, 2, and 3.
For 1/10 IPV-Al, the seroconversion rates for the different poliovirus types were 98.5% (type 1), 94.6% (type 2), and 99.5% (type 3), compared with 100% (type 1), 98.5% (type 2), and 100% (type 3) for IPV.
This and the results from other studies “have paved the way for further clinical investigations of IPV-Al in phase III trials,” Dr. Rivera and his associates wrote.
“The low frequency of adverse events in this phase II trial suggests that a safety evaluation is not necessarily justified,” they concluded.
The Bill & Melinda Gates Foundation funded the study. The authors had no disclosures.
Read more in the Lancet Infectious Diseases (2017 Apr 25. doi: 10.1016/S1473-3099(17)30177-9).
Aluminum hydroxide–adjuvanted vaccines with reduced doses of inactivated polio vaccine (IPV-Al) were noninferior to standard inactivated poliovirus vaccine (IPV) in a large trial in the Dominican Republic, said Luis Rivera, MD, of the Hospital Maternidad Nuestra Señora de la Altagracia, Santo Domingo, Dominican Republic, and his associates.
If these findings are replicated in phase III trials and regulatory approval follows, such vaccines could be low-cost replacements for standard IPV and oral poliovirus vaccines in low-resource countries, the study authors suggested.
In this phase II, blinded, randomized trial with three investigational IPV-Al groups and one IPV group, the vaccines were given at 6 weeks, 10 weeks, 14 weeks, and 18 weeks to 823 infants who had not previously received any polio vaccination. The three new IPV-Al vaccines all proved to be noninferior to IPV for poliovirus types 1, 2, and 3.
For 1/10 IPV-Al, the seroconversion rates for the different poliovirus types were 98.5% (type 1), 94.6% (type 2), and 99.5% (type 3), compared with 100% (type 1), 98.5% (type 2), and 100% (type 3) for IPV.
This and the results from other studies “have paved the way for further clinical investigations of IPV-Al in phase III trials,” Dr. Rivera and his associates wrote.
“The low frequency of adverse events in this phase II trial suggests that a safety evaluation is not necessarily justified,” they concluded.
The Bill & Melinda Gates Foundation funded the study. The authors had no disclosures.
Read more in the Lancet Infectious Diseases (2017 Apr 25. doi: 10.1016/S1473-3099(17)30177-9).
FROM THE LANCET INFECTIOUS DISEASES
Antacid use in infants linked to increased fracture risk
SAN FRANCISCO – Children were more likely to experience a fracture if they were prescribed antacids before age 1 year, according to a study of military families.
The large study revealed that use of proton pump inhibitors (PPIs) before age 1 year was linked to a 22% increased risk of fracture, compared with those not prescribed antacids. Similarly, children prescribed both PPIs and H2 blockers before age 1 year were 31% more likely to have a fracture compared to those not taking the drugs.
“A lot of data are coming out that proton pump inhibitors are not quite as benign as we used to think, and we are seeing that fracture risk is increased with use,” U.S. Air Force Capt. Laura Malchodi, MD, a pediatrics resident at Walter Reed National Military Medical Center in Bethesda, Md., told colleagues at the Pediatric Academic Societies meeting.
Antacid use has been increasing among both adults and children, but the biggest rise has been in children under age 1 year, she said. Previous research into adult use of antacids has revealed an increased incidence of fractures, so Dr. Malchodi investigated the incidence of fractures in children under age 1 year among those who had taken PPIs, H2 blockers, neither, or both.
“What this means for doctors is that when you do start to think of using proton pump inhibitors or any antacid therapy in children, we should really think of limiting it to one type if possible – H2 blockers are now preferable – and for the shortest amount of time as possible,” Dr. Malchodi said of her findings.
The retrospective study’s cohort comprised 874,447 children born between 2001 and 2013 who had been in the U.S. Military Health System for at least 2 years. Children who took antacids after age 1, spent more than a week in a neonatal intensive care unit, or had nonaccidental trauma (abuse) or osteogenesis imperfecta were excluded.
Ninety percent of the cohort had not received prescriptions for any antacids (789,631 children) in their first year of life, and 1.2% had received prescriptions for both PPIs and H2 blockers before age 1 year. Of the remaining children, 7.7% had received prescriptions for H2 blockers, and 0.8% for PPIs.
The children who had and had not been prescribed antacids were similar in median years enrolled in the system, but nearly twice as many who received antacid prescription had been preterm (6.4% vs. 3.5%, P less than .05). Similarly, 3.7% of those prescribed antacids had a low birth weight, compared with 2.2% of those not prescribed antacids (P less than .05). The median age of fracture also differed for the two groups: 3.9 years for those prescribed antacids and 4.5 years for those not (P less than .05).
In using medical records during their analysis, the researchers excluded follow-up visits for the same fracture within the previous 6 months. Before adjustment for covariates, boys had a slightly increased risk of fracture (hazard ratio [HR], 1.08), and those with a previous fracture had an 85% increased risk (HR, 1.85). Compared with children not prescribed antacids, those prescribed PPIs had a 23% increased risk of fracture (HR, 1.23), and those prescribed H2 blockers had a 13% increased risk (HR, 1.13). Those prescribed combination antacid therapy had a 32% increased risk of fractures (HR, 1.32).
Adjustment for preterm birth, low birth weight, sex, and a previous fracture barely reduced those risks: 22% increased risk for PPI use, 4% increased risk for H2 blocker use, and 31% increased risk for using both. The vast majority of children who took antacids had been prescribed them in their first 6 months, so the researchers calculated adjusted risk by age of exposure. For H2 blockers, no statistically significant increased risk of fracture existed in those taking them before or after 6 months old.
Those taking PPIs, however, had a 25% increased risk of fracture if they took them before 6 months old, compared with a 20% increased risk if prescribed PPIs between 6 and 12 months. Likewise, children taking both PPIs and H2 blockers before 6 months old had a 32% increased risk of fracture, compared with a 23% increased risk between 6 and 12 months old.
Analysis of the duration of children’s use of antacids revealed a dose-response relationship, with an increasing risk alongside increasing days taking the medication. For example, those on PPIs for a month or less had a 19% increased risk of fracture, compared with children not prescribed antacids, but that rose to a 23% increased risk for those taking PPIs from 60 to 150 days and to a 42% increased risk for taking them longer than 150 days.
Similarly, the risk of fracture after having taken H2 blockers for up to a month was 14%, which increased to 22% for medication durations over 120 days. Children on combination therapy took the medication for much longer than did children prescribed either antacid. The risk of fracture was 17% greater for those taking them for up to 4 months, but that increased to a 50% greater risk for children taking both antacids for longer than 338 days.
“A couple of decades ago, we thought these medications were super safe, that there could be no problem with them,” Dr. Malchodi said, suggesting that their availability over the counter for adults may contribute to that perception. “With this growing evidence, there’s at least a lot more caution about using them,” she said.
Because the study relied on prescriptions for antacids, the researchers could not take into account which children actually took the antacids. Another limitation was their inability to consider other potential confounders, such as socioeconomic status or comorbidities that may later increase the risk of fracture. Further, exclusion of 6 months of follow-up after one fracture may have missed new fractures in that time period. Using a military cohort, on the other hand, meant having a geographically and socioeconomically diverse population with less risk of care bias because all the children had universal health care coverage.
No external funding was used. Dr. Malchodi reported having no disclosures.
*The View on the News was added on 6/13/17.
Acid suppression is frequently prescribed in infants for the treatment of symptoms such as fussiness, arching, and poor feeding, despite randomized controlled trials showing no benefit for these symptoms over placebo. These medications are often prescribed because physicians think they are useful; families are frustrated, exhausted, and worried about the infant’s symptoms; and these medications are considered safe and well tolerated. Recent adult studies have raised the possibility that these medications may not be as safe as once thought, with case-controlled studies linking them to increased risk of infectious, renal, cardiac, neurologic, and orthopedic complications. While there are pediatric studies supporting an increased infectious risk from both PPI and H2 antagonist use, there are no pediatric studies that address other complications. In this study by Dr. Malchodi et al., acid suppression use in infants under the age of 1 year was associated with an increased risk of fractures over the duration of enrollment in the U.S. Military Health System. They also found a dose-dependent effect, which further strengthens the conclusions that acid suppression may predispose patients to fractures. This research is a critical first step in elucidating the relationship of acid suppression and fracture risk in infants.
As with all database studies, there are some limitations to this study. First, patients taking acid suppression often have more comorbidities than do patients who are not taking the medications; because these patients are sicker, they may have more risk factors including compromised nutritional status and malabsorption predisposing them to fractures. The authors controlled for some of these comorbidities, but future studies should address additional ones. Second, as with all case-control studies, proving causality, not just association, is difficult so any future prospective acid suppression trials should include an assessment of bone health. Third, because the dosing per kilogram is not included, it is difficult to determine if there is a safe level of acid suppression for those children who need it. Fourth, because this is a database review, it is not clear if patients actually took the prescribed medication.
Because of the safety concerns regarding acid suppression as well as the lack of benefit in reducing symptoms in infants, nonpharmacologic therapies should be considered as first-line therapy for the treatment of bothersome symptoms. In the fussy, arching, or irritable child, changing the frequency or volume of feeds, thickening feeds, or changing to partially hydrolyzed formulas or eliminating dairy from the maternal diet (for breastfed infants) should be considered before starting acid suppression therapy. Other diagnoses besides gastroesophageal reflux disease, such as colic and cow’s milk protein allergy, need to be considered as well to ensure that the therapy matches the diagnosis. For those patients in whom acid suppression is required, using the lowest dose possible for the shortest amount of time is critical. Finally, for patients on multiple medications that may impact fracture risk (such as acid suppression, steroids), extra vigilance is needed to stop unnecessary medications as soon as possible.
Acid suppression is frequently prescribed in infants for the treatment of symptoms such as fussiness, arching, and poor feeding, despite randomized controlled trials showing no benefit for these symptoms over placebo. These medications are often prescribed because physicians think they are useful; families are frustrated, exhausted, and worried about the infant’s symptoms; and these medications are considered safe and well tolerated. Recent adult studies have raised the possibility that these medications may not be as safe as once thought, with case-controlled studies linking them to increased risk of infectious, renal, cardiac, neurologic, and orthopedic complications. While there are pediatric studies supporting an increased infectious risk from both PPI and H2 antagonist use, there are no pediatric studies that address other complications. In this study by Dr. Malchodi et al., acid suppression use in infants under the age of 1 year was associated with an increased risk of fractures over the duration of enrollment in the U.S. Military Health System. They also found a dose-dependent effect, which further strengthens the conclusions that acid suppression may predispose patients to fractures. This research is a critical first step in elucidating the relationship of acid suppression and fracture risk in infants.
As with all database studies, there are some limitations to this study. First, patients taking acid suppression often have more comorbidities than do patients who are not taking the medications; because these patients are sicker, they may have more risk factors including compromised nutritional status and malabsorption predisposing them to fractures. The authors controlled for some of these comorbidities, but future studies should address additional ones. Second, as with all case-control studies, proving causality, not just association, is difficult so any future prospective acid suppression trials should include an assessment of bone health. Third, because the dosing per kilogram is not included, it is difficult to determine if there is a safe level of acid suppression for those children who need it. Fourth, because this is a database review, it is not clear if patients actually took the prescribed medication.
Because of the safety concerns regarding acid suppression as well as the lack of benefit in reducing symptoms in infants, nonpharmacologic therapies should be considered as first-line therapy for the treatment of bothersome symptoms. In the fussy, arching, or irritable child, changing the frequency or volume of feeds, thickening feeds, or changing to partially hydrolyzed formulas or eliminating dairy from the maternal diet (for breastfed infants) should be considered before starting acid suppression therapy. Other diagnoses besides gastroesophageal reflux disease, such as colic and cow’s milk protein allergy, need to be considered as well to ensure that the therapy matches the diagnosis. For those patients in whom acid suppression is required, using the lowest dose possible for the shortest amount of time is critical. Finally, for patients on multiple medications that may impact fracture risk (such as acid suppression, steroids), extra vigilance is needed to stop unnecessary medications as soon as possible.
Acid suppression is frequently prescribed in infants for the treatment of symptoms such as fussiness, arching, and poor feeding, despite randomized controlled trials showing no benefit for these symptoms over placebo. These medications are often prescribed because physicians think they are useful; families are frustrated, exhausted, and worried about the infant’s symptoms; and these medications are considered safe and well tolerated. Recent adult studies have raised the possibility that these medications may not be as safe as once thought, with case-controlled studies linking them to increased risk of infectious, renal, cardiac, neurologic, and orthopedic complications. While there are pediatric studies supporting an increased infectious risk from both PPI and H2 antagonist use, there are no pediatric studies that address other complications. In this study by Dr. Malchodi et al., acid suppression use in infants under the age of 1 year was associated with an increased risk of fractures over the duration of enrollment in the U.S. Military Health System. They also found a dose-dependent effect, which further strengthens the conclusions that acid suppression may predispose patients to fractures. This research is a critical first step in elucidating the relationship of acid suppression and fracture risk in infants.
As with all database studies, there are some limitations to this study. First, patients taking acid suppression often have more comorbidities than do patients who are not taking the medications; because these patients are sicker, they may have more risk factors including compromised nutritional status and malabsorption predisposing them to fractures. The authors controlled for some of these comorbidities, but future studies should address additional ones. Second, as with all case-control studies, proving causality, not just association, is difficult so any future prospective acid suppression trials should include an assessment of bone health. Third, because the dosing per kilogram is not included, it is difficult to determine if there is a safe level of acid suppression for those children who need it. Fourth, because this is a database review, it is not clear if patients actually took the prescribed medication.
Because of the safety concerns regarding acid suppression as well as the lack of benefit in reducing symptoms in infants, nonpharmacologic therapies should be considered as first-line therapy for the treatment of bothersome symptoms. In the fussy, arching, or irritable child, changing the frequency or volume of feeds, thickening feeds, or changing to partially hydrolyzed formulas or eliminating dairy from the maternal diet (for breastfed infants) should be considered before starting acid suppression therapy. Other diagnoses besides gastroesophageal reflux disease, such as colic and cow’s milk protein allergy, need to be considered as well to ensure that the therapy matches the diagnosis. For those patients in whom acid suppression is required, using the lowest dose possible for the shortest amount of time is critical. Finally, for patients on multiple medications that may impact fracture risk (such as acid suppression, steroids), extra vigilance is needed to stop unnecessary medications as soon as possible.
SAN FRANCISCO – Children were more likely to experience a fracture if they were prescribed antacids before age 1 year, according to a study of military families.
The large study revealed that use of proton pump inhibitors (PPIs) before age 1 year was linked to a 22% increased risk of fracture, compared with those not prescribed antacids. Similarly, children prescribed both PPIs and H2 blockers before age 1 year were 31% more likely to have a fracture compared to those not taking the drugs.
“A lot of data are coming out that proton pump inhibitors are not quite as benign as we used to think, and we are seeing that fracture risk is increased with use,” U.S. Air Force Capt. Laura Malchodi, MD, a pediatrics resident at Walter Reed National Military Medical Center in Bethesda, Md., told colleagues at the Pediatric Academic Societies meeting.
Antacid use has been increasing among both adults and children, but the biggest rise has been in children under age 1 year, she said. Previous research into adult use of antacids has revealed an increased incidence of fractures, so Dr. Malchodi investigated the incidence of fractures in children under age 1 year among those who had taken PPIs, H2 blockers, neither, or both.
“What this means for doctors is that when you do start to think of using proton pump inhibitors or any antacid therapy in children, we should really think of limiting it to one type if possible – H2 blockers are now preferable – and for the shortest amount of time as possible,” Dr. Malchodi said of her findings.
The retrospective study’s cohort comprised 874,447 children born between 2001 and 2013 who had been in the U.S. Military Health System for at least 2 years. Children who took antacids after age 1, spent more than a week in a neonatal intensive care unit, or had nonaccidental trauma (abuse) or osteogenesis imperfecta were excluded.
Ninety percent of the cohort had not received prescriptions for any antacids (789,631 children) in their first year of life, and 1.2% had received prescriptions for both PPIs and H2 blockers before age 1 year. Of the remaining children, 7.7% had received prescriptions for H2 blockers, and 0.8% for PPIs.
The children who had and had not been prescribed antacids were similar in median years enrolled in the system, but nearly twice as many who received antacid prescription had been preterm (6.4% vs. 3.5%, P less than .05). Similarly, 3.7% of those prescribed antacids had a low birth weight, compared with 2.2% of those not prescribed antacids (P less than .05). The median age of fracture also differed for the two groups: 3.9 years for those prescribed antacids and 4.5 years for those not (P less than .05).
In using medical records during their analysis, the researchers excluded follow-up visits for the same fracture within the previous 6 months. Before adjustment for covariates, boys had a slightly increased risk of fracture (hazard ratio [HR], 1.08), and those with a previous fracture had an 85% increased risk (HR, 1.85). Compared with children not prescribed antacids, those prescribed PPIs had a 23% increased risk of fracture (HR, 1.23), and those prescribed H2 blockers had a 13% increased risk (HR, 1.13). Those prescribed combination antacid therapy had a 32% increased risk of fractures (HR, 1.32).
Adjustment for preterm birth, low birth weight, sex, and a previous fracture barely reduced those risks: 22% increased risk for PPI use, 4% increased risk for H2 blocker use, and 31% increased risk for using both. The vast majority of children who took antacids had been prescribed them in their first 6 months, so the researchers calculated adjusted risk by age of exposure. For H2 blockers, no statistically significant increased risk of fracture existed in those taking them before or after 6 months old.
Those taking PPIs, however, had a 25% increased risk of fracture if they took them before 6 months old, compared with a 20% increased risk if prescribed PPIs between 6 and 12 months. Likewise, children taking both PPIs and H2 blockers before 6 months old had a 32% increased risk of fracture, compared with a 23% increased risk between 6 and 12 months old.
Analysis of the duration of children’s use of antacids revealed a dose-response relationship, with an increasing risk alongside increasing days taking the medication. For example, those on PPIs for a month or less had a 19% increased risk of fracture, compared with children not prescribed antacids, but that rose to a 23% increased risk for those taking PPIs from 60 to 150 days and to a 42% increased risk for taking them longer than 150 days.
Similarly, the risk of fracture after having taken H2 blockers for up to a month was 14%, which increased to 22% for medication durations over 120 days. Children on combination therapy took the medication for much longer than did children prescribed either antacid. The risk of fracture was 17% greater for those taking them for up to 4 months, but that increased to a 50% greater risk for children taking both antacids for longer than 338 days.
“A couple of decades ago, we thought these medications were super safe, that there could be no problem with them,” Dr. Malchodi said, suggesting that their availability over the counter for adults may contribute to that perception. “With this growing evidence, there’s at least a lot more caution about using them,” she said.
Because the study relied on prescriptions for antacids, the researchers could not take into account which children actually took the antacids. Another limitation was their inability to consider other potential confounders, such as socioeconomic status or comorbidities that may later increase the risk of fracture. Further, exclusion of 6 months of follow-up after one fracture may have missed new fractures in that time period. Using a military cohort, on the other hand, meant having a geographically and socioeconomically diverse population with less risk of care bias because all the children had universal health care coverage.
No external funding was used. Dr. Malchodi reported having no disclosures.
*The View on the News was added on 6/13/17.
SAN FRANCISCO – Children were more likely to experience a fracture if they were prescribed antacids before age 1 year, according to a study of military families.
The large study revealed that use of proton pump inhibitors (PPIs) before age 1 year was linked to a 22% increased risk of fracture, compared with those not prescribed antacids. Similarly, children prescribed both PPIs and H2 blockers before age 1 year were 31% more likely to have a fracture compared to those not taking the drugs.
“A lot of data are coming out that proton pump inhibitors are not quite as benign as we used to think, and we are seeing that fracture risk is increased with use,” U.S. Air Force Capt. Laura Malchodi, MD, a pediatrics resident at Walter Reed National Military Medical Center in Bethesda, Md., told colleagues at the Pediatric Academic Societies meeting.
Antacid use has been increasing among both adults and children, but the biggest rise has been in children under age 1 year, she said. Previous research into adult use of antacids has revealed an increased incidence of fractures, so Dr. Malchodi investigated the incidence of fractures in children under age 1 year among those who had taken PPIs, H2 blockers, neither, or both.
“What this means for doctors is that when you do start to think of using proton pump inhibitors or any antacid therapy in children, we should really think of limiting it to one type if possible – H2 blockers are now preferable – and for the shortest amount of time as possible,” Dr. Malchodi said of her findings.
The retrospective study’s cohort comprised 874,447 children born between 2001 and 2013 who had been in the U.S. Military Health System for at least 2 years. Children who took antacids after age 1, spent more than a week in a neonatal intensive care unit, or had nonaccidental trauma (abuse) or osteogenesis imperfecta were excluded.
Ninety percent of the cohort had not received prescriptions for any antacids (789,631 children) in their first year of life, and 1.2% had received prescriptions for both PPIs and H2 blockers before age 1 year. Of the remaining children, 7.7% had received prescriptions for H2 blockers, and 0.8% for PPIs.
The children who had and had not been prescribed antacids were similar in median years enrolled in the system, but nearly twice as many who received antacid prescription had been preterm (6.4% vs. 3.5%, P less than .05). Similarly, 3.7% of those prescribed antacids had a low birth weight, compared with 2.2% of those not prescribed antacids (P less than .05). The median age of fracture also differed for the two groups: 3.9 years for those prescribed antacids and 4.5 years for those not (P less than .05).
In using medical records during their analysis, the researchers excluded follow-up visits for the same fracture within the previous 6 months. Before adjustment for covariates, boys had a slightly increased risk of fracture (hazard ratio [HR], 1.08), and those with a previous fracture had an 85% increased risk (HR, 1.85). Compared with children not prescribed antacids, those prescribed PPIs had a 23% increased risk of fracture (HR, 1.23), and those prescribed H2 blockers had a 13% increased risk (HR, 1.13). Those prescribed combination antacid therapy had a 32% increased risk of fractures (HR, 1.32).
Adjustment for preterm birth, low birth weight, sex, and a previous fracture barely reduced those risks: 22% increased risk for PPI use, 4% increased risk for H2 blocker use, and 31% increased risk for using both. The vast majority of children who took antacids had been prescribed them in their first 6 months, so the researchers calculated adjusted risk by age of exposure. For H2 blockers, no statistically significant increased risk of fracture existed in those taking them before or after 6 months old.
Those taking PPIs, however, had a 25% increased risk of fracture if they took them before 6 months old, compared with a 20% increased risk if prescribed PPIs between 6 and 12 months. Likewise, children taking both PPIs and H2 blockers before 6 months old had a 32% increased risk of fracture, compared with a 23% increased risk between 6 and 12 months old.
Analysis of the duration of children’s use of antacids revealed a dose-response relationship, with an increasing risk alongside increasing days taking the medication. For example, those on PPIs for a month or less had a 19% increased risk of fracture, compared with children not prescribed antacids, but that rose to a 23% increased risk for those taking PPIs from 60 to 150 days and to a 42% increased risk for taking them longer than 150 days.
Similarly, the risk of fracture after having taken H2 blockers for up to a month was 14%, which increased to 22% for medication durations over 120 days. Children on combination therapy took the medication for much longer than did children prescribed either antacid. The risk of fracture was 17% greater for those taking them for up to 4 months, but that increased to a 50% greater risk for children taking both antacids for longer than 338 days.
“A couple of decades ago, we thought these medications were super safe, that there could be no problem with them,” Dr. Malchodi said, suggesting that their availability over the counter for adults may contribute to that perception. “With this growing evidence, there’s at least a lot more caution about using them,” she said.
Because the study relied on prescriptions for antacids, the researchers could not take into account which children actually took the antacids. Another limitation was their inability to consider other potential confounders, such as socioeconomic status or comorbidities that may later increase the risk of fracture. Further, exclusion of 6 months of follow-up after one fracture may have missed new fractures in that time period. Using a military cohort, on the other hand, meant having a geographically and socioeconomically diverse population with less risk of care bias because all the children had universal health care coverage.
No external funding was used. Dr. Malchodi reported having no disclosures.
*The View on the News was added on 6/13/17.
AT PAS 17
Key clinical point:
Major finding: Risk of fracture increased 22% among children who took proton pump inhibitors in their first year of life and increased 31% among children taking both PPIs and H2 blockers.
Data source: A retrospective cohort study of 874,447 children born between 2001 and 2013 and who were in the U.S. Military Health System for at least 2 years.
Disclosures: No external funding was used. Dr. Malchodi reported having no relevant financial disclosures.
Adalimumab is good first-line anti-TNF therapy for pediatric Crohn’s disease
Adalimumab (ADA) as a first-line anti–tumor necrosis factor therapy induced and maintained clinical remission in children with Crohn’s disease, said Víctor Manuel Navas-López, MD, PhD, of the Hospital Materno Infantil, Málaga, Spain, and his associates.
Infliximab is the usual first-line anti–tumor necrosis factor treatment given to children with Crohn’s disease, with ADA used in patients who don’t respond or who develop tolerance to infliximab.
Dose escalation was necessary for 26% of the 62 patients. Thirty-nine percent of patients had growth retardation.
“ADA treatment significantly improved z-score growth rate in children with Crohn’s disease, especially in those with severe growth failure at baseline,” the researchers said. Only 13% of patients reported adverse events, none of them severe.
Read more in the Anales de Pediatría (2017 Apr 14. doi: 10.1016/j.anpedi.2017.01.013).
Adalimumab (ADA) as a first-line anti–tumor necrosis factor therapy induced and maintained clinical remission in children with Crohn’s disease, said Víctor Manuel Navas-López, MD, PhD, of the Hospital Materno Infantil, Málaga, Spain, and his associates.
Infliximab is the usual first-line anti–tumor necrosis factor treatment given to children with Crohn’s disease, with ADA used in patients who don’t respond or who develop tolerance to infliximab.
Dose escalation was necessary for 26% of the 62 patients. Thirty-nine percent of patients had growth retardation.
“ADA treatment significantly improved z-score growth rate in children with Crohn’s disease, especially in those with severe growth failure at baseline,” the researchers said. Only 13% of patients reported adverse events, none of them severe.
Read more in the Anales de Pediatría (2017 Apr 14. doi: 10.1016/j.anpedi.2017.01.013).
Adalimumab (ADA) as a first-line anti–tumor necrosis factor therapy induced and maintained clinical remission in children with Crohn’s disease, said Víctor Manuel Navas-López, MD, PhD, of the Hospital Materno Infantil, Málaga, Spain, and his associates.
Infliximab is the usual first-line anti–tumor necrosis factor treatment given to children with Crohn’s disease, with ADA used in patients who don’t respond or who develop tolerance to infliximab.
Dose escalation was necessary for 26% of the 62 patients. Thirty-nine percent of patients had growth retardation.
“ADA treatment significantly improved z-score growth rate in children with Crohn’s disease, especially in those with severe growth failure at baseline,” the researchers said. Only 13% of patients reported adverse events, none of them severe.
Read more in the Anales de Pediatría (2017 Apr 14. doi: 10.1016/j.anpedi.2017.01.013).
FROM ANALES DE PEDIATRIA