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CDC: First-trimester Zika infection had highest rate of birth defects
One in 12 infant or fetus born to mothers from the U.S. territories with laboratory-confirmed Zika infection during the first trimester had a birth defect possibly-associated with the infection, officials from the Centers for Disease Control and Prevention reported.
Overall, there were 3,930 pregnant women with laboratory evidence of possible Zika infection reported in the U.S. territories during Jan. 1, 2016-May 24, 2017. Of the 2,549 completed pregnancies, 122 resulted in a fetus or infant with possible Zika-related birth defects. The greatest number of birth defects was for maternal infections in the first trimester at 8%, followed by 5% in the second trimester, and 4% in the third trimester (MMWR. 2017, June 8. doi: 10.15585/mmwr.mm6623e1).
“These data indicate that Zika virus is associated with risks to pregnant women and their babies, even when the infection is identified later during pregnancy,” Dr. Schuchat said. “Although we are still learning about the full range of birth defects that can occur within a woman infected with Zika during pregnancy, we know that it causes brain abnormalities, vision problems, and other consequences of brain damage that might require long-term specialized care.”
In depth analysis of Zika side effects among the studied population found that 108 (89%) of the 122 fetuses or infants with infection confirmed by nucleic acid testing were diagnosed with brain abnormalities and/or microcephaly.
Researchers also found potential gaps in the evaluation of infants at birth with possible congenital Zika virus infections in the U.S. territories, according to Peggy Honein, PhD, a coleader of the CDC Pregnancy and Birth Defects Task Force.
“There are still opportunities to ensure every health care provider is aware of how to screen for exposure to Zika, the need for comprehensive evaluation of infants, and how to monitor and provide follow-up care,” Dr. Honein said. “Identification and follow-ups with laboratory evidence of Zika infection during pregnancy can facilitate timely and appropriate clinical intervention services and help assess their future needs.”
This research was limited by the size of the population analyzed, which was small and, therefore, may not be the full scope of the Zika population. The clinical guidance for infants was also changed in August of 2016, which may have affected reporting, officials said.
To help collect more accurate data, U.S. territories will begin using the same standard case definition as used by the U.S. states and Washington, DC starting June 22, 2017.
One of the investigators reported personal fees from Population Services International, Dexis Consulting Group, and Public Health Institute outside the submitted work. The other investigators reported no relevant financial disclosures.
ezimmerman@frontlinemedcom.com
On Twitter @eaztweets
One in 12 infant or fetus born to mothers from the U.S. territories with laboratory-confirmed Zika infection during the first trimester had a birth defect possibly-associated with the infection, officials from the Centers for Disease Control and Prevention reported.
Overall, there were 3,930 pregnant women with laboratory evidence of possible Zika infection reported in the U.S. territories during Jan. 1, 2016-May 24, 2017. Of the 2,549 completed pregnancies, 122 resulted in a fetus or infant with possible Zika-related birth defects. The greatest number of birth defects was for maternal infections in the first trimester at 8%, followed by 5% in the second trimester, and 4% in the third trimester (MMWR. 2017, June 8. doi: 10.15585/mmwr.mm6623e1).
“These data indicate that Zika virus is associated with risks to pregnant women and their babies, even when the infection is identified later during pregnancy,” Dr. Schuchat said. “Although we are still learning about the full range of birth defects that can occur within a woman infected with Zika during pregnancy, we know that it causes brain abnormalities, vision problems, and other consequences of brain damage that might require long-term specialized care.”
In depth analysis of Zika side effects among the studied population found that 108 (89%) of the 122 fetuses or infants with infection confirmed by nucleic acid testing were diagnosed with brain abnormalities and/or microcephaly.
Researchers also found potential gaps in the evaluation of infants at birth with possible congenital Zika virus infections in the U.S. territories, according to Peggy Honein, PhD, a coleader of the CDC Pregnancy and Birth Defects Task Force.
“There are still opportunities to ensure every health care provider is aware of how to screen for exposure to Zika, the need for comprehensive evaluation of infants, and how to monitor and provide follow-up care,” Dr. Honein said. “Identification and follow-ups with laboratory evidence of Zika infection during pregnancy can facilitate timely and appropriate clinical intervention services and help assess their future needs.”
This research was limited by the size of the population analyzed, which was small and, therefore, may not be the full scope of the Zika population. The clinical guidance for infants was also changed in August of 2016, which may have affected reporting, officials said.
To help collect more accurate data, U.S. territories will begin using the same standard case definition as used by the U.S. states and Washington, DC starting June 22, 2017.
One of the investigators reported personal fees from Population Services International, Dexis Consulting Group, and Public Health Institute outside the submitted work. The other investigators reported no relevant financial disclosures.
ezimmerman@frontlinemedcom.com
On Twitter @eaztweets
One in 12 infant or fetus born to mothers from the U.S. territories with laboratory-confirmed Zika infection during the first trimester had a birth defect possibly-associated with the infection, officials from the Centers for Disease Control and Prevention reported.
Overall, there were 3,930 pregnant women with laboratory evidence of possible Zika infection reported in the U.S. territories during Jan. 1, 2016-May 24, 2017. Of the 2,549 completed pregnancies, 122 resulted in a fetus or infant with possible Zika-related birth defects. The greatest number of birth defects was for maternal infections in the first trimester at 8%, followed by 5% in the second trimester, and 4% in the third trimester (MMWR. 2017, June 8. doi: 10.15585/mmwr.mm6623e1).
“These data indicate that Zika virus is associated with risks to pregnant women and their babies, even when the infection is identified later during pregnancy,” Dr. Schuchat said. “Although we are still learning about the full range of birth defects that can occur within a woman infected with Zika during pregnancy, we know that it causes brain abnormalities, vision problems, and other consequences of brain damage that might require long-term specialized care.”
In depth analysis of Zika side effects among the studied population found that 108 (89%) of the 122 fetuses or infants with infection confirmed by nucleic acid testing were diagnosed with brain abnormalities and/or microcephaly.
Researchers also found potential gaps in the evaluation of infants at birth with possible congenital Zika virus infections in the U.S. territories, according to Peggy Honein, PhD, a coleader of the CDC Pregnancy and Birth Defects Task Force.
“There are still opportunities to ensure every health care provider is aware of how to screen for exposure to Zika, the need for comprehensive evaluation of infants, and how to monitor and provide follow-up care,” Dr. Honein said. “Identification and follow-ups with laboratory evidence of Zika infection during pregnancy can facilitate timely and appropriate clinical intervention services and help assess their future needs.”
This research was limited by the size of the population analyzed, which was small and, therefore, may not be the full scope of the Zika population. The clinical guidance for infants was also changed in August of 2016, which may have affected reporting, officials said.
To help collect more accurate data, U.S. territories will begin using the same standard case definition as used by the U.S. states and Washington, DC starting June 22, 2017.
One of the investigators reported personal fees from Population Services International, Dexis Consulting Group, and Public Health Institute outside the submitted work. The other investigators reported no relevant financial disclosures.
ezimmerman@frontlinemedcom.com
On Twitter @eaztweets
FROM MMWR
The changing face of JIA sets the tone for pediatric sessions at EULAR
The heterogeneous nature of juvenile idiopathic arthritis (JIA), the use of biologics in childhood rheumatic diseases, and a look at the long-term outcomes for children with JIA are just some of the highlights from the pediatric rheumatology sessions at this year’s EULAR Congress in Madrid, June 14-17.
EULAR Standing Committee Chairperson for Paediatric Rheumatology Tadej Avcin, MD, PhD, said that a bench-to-bedside session on the heterogeneity of JIA on the afternoon of Thursday, June 15, would explore the biologic basis of the disease, the role of cytokine profiling, and the clinical variability in the disease.
“By highlighting the heterogeneity of JIA, we hope this session will contribute to the further understanding of differences between JIA subtypes, as well as contribute some scientific background for the further classification of children with JIA,” he said.
Another “not to miss” session from the pediatric program that will be held on the afternoon of Friday, June 16, is the open issues session on the use of biologic agents in JIA, according to Dr. Avcin, professor of pediatrics and head of the department of allergology, rheumatology, and clinical immunology at University Children’s Hospital, University Medical Center, Ljubljana, Slovenia.
Speaking on the long-term side effects of biologics, Joost Swart, MD, from Utrecht in the Netherlands will present some novel data from the large ongoing pharmacovigilance project Pharmachild that follows children aged 3-10 years who have been treated with methotrexate or a biologic.
At the same session, Pierre Quartier, MD, from Paris will take delegates through data on autoimmune phenomena that can occur in children who are on biologic treatment.
“We know that, in treating children with biologics, they can sometimes develop antidrug antibodies and various induced autoimmune phenomena. We would like to highlight this aspect so that physicians can have more of an overview of possible immune-mediated adverse effects in their patients,” Dr. Avcin said.
The session will also address what Dr. Avcin describes as an emerging and important clinical question: When and how do you discontinue treatment in children with sustained remission?
It’s a question he hopes Gerd Horneff, MD, from Germany will be able to shed some light on when he shares data on how frequently children experience disease flares after discontinuing treatment.
Another pediatric highlight is a morning session on Saturday, June 17, that will address the long-term outcomes of children with JIA.
A presentation by Marion van Rossum, MD, PhD, from the Netherlands will explore whether there are certain clinical or laboratory markers that can help identify children who are more likely to respond well to treatment, compared with other children.
Dirk Foell, MD, from Germany will follow with a session on immunological markers of remission in JIA.
As Dr. Avcin explained, immunological markers such as S100 proteins have shown promise as a biomarker of subclinical active disease.
“Even if a child appears to have clinically inactive disease, elevated levels of these markers may help predict which children will remain in remission after discontinuing treatment and which children may be at an increased risk of a disease flare,” he said.
Rounding off the session, Berit Flatø, MD, PhD, from Norway will present delegates with data from an epidemiological study of long-term outcomes of children with JIA as they move into adulthood.
“Dr. Flatø will present the long-term outcome data from children followed for up to 20 years,” Dr. Avcin said. “Biologics have been in pediatric rheumatology for around 17 years so we will be able to see what is the outcome of children with JIA moving into adulthood with our current treatment protocols.”
In the afternoon, on Friday, pediatric experts will team up with their adult rheumatology colleagues in a “challenges in clinical practice” session to update delegates on life-threatening presentations of rheumatic diseases.
“We will highlight life-threatening presentations that are of particular interest in children, like macrophage activation syndrome and complications of systemic connective tissue diseases and systemic vasculitides like Kawasaki disease and Takayasu’s arteritis,” Dr. Avcin said.
The heterogeneous nature of juvenile idiopathic arthritis (JIA), the use of biologics in childhood rheumatic diseases, and a look at the long-term outcomes for children with JIA are just some of the highlights from the pediatric rheumatology sessions at this year’s EULAR Congress in Madrid, June 14-17.
EULAR Standing Committee Chairperson for Paediatric Rheumatology Tadej Avcin, MD, PhD, said that a bench-to-bedside session on the heterogeneity of JIA on the afternoon of Thursday, June 15, would explore the biologic basis of the disease, the role of cytokine profiling, and the clinical variability in the disease.
“By highlighting the heterogeneity of JIA, we hope this session will contribute to the further understanding of differences between JIA subtypes, as well as contribute some scientific background for the further classification of children with JIA,” he said.
Another “not to miss” session from the pediatric program that will be held on the afternoon of Friday, June 16, is the open issues session on the use of biologic agents in JIA, according to Dr. Avcin, professor of pediatrics and head of the department of allergology, rheumatology, and clinical immunology at University Children’s Hospital, University Medical Center, Ljubljana, Slovenia.
Speaking on the long-term side effects of biologics, Joost Swart, MD, from Utrecht in the Netherlands will present some novel data from the large ongoing pharmacovigilance project Pharmachild that follows children aged 3-10 years who have been treated with methotrexate or a biologic.
At the same session, Pierre Quartier, MD, from Paris will take delegates through data on autoimmune phenomena that can occur in children who are on biologic treatment.
“We know that, in treating children with biologics, they can sometimes develop antidrug antibodies and various induced autoimmune phenomena. We would like to highlight this aspect so that physicians can have more of an overview of possible immune-mediated adverse effects in their patients,” Dr. Avcin said.
The session will also address what Dr. Avcin describes as an emerging and important clinical question: When and how do you discontinue treatment in children with sustained remission?
It’s a question he hopes Gerd Horneff, MD, from Germany will be able to shed some light on when he shares data on how frequently children experience disease flares after discontinuing treatment.
Another pediatric highlight is a morning session on Saturday, June 17, that will address the long-term outcomes of children with JIA.
A presentation by Marion van Rossum, MD, PhD, from the Netherlands will explore whether there are certain clinical or laboratory markers that can help identify children who are more likely to respond well to treatment, compared with other children.
Dirk Foell, MD, from Germany will follow with a session on immunological markers of remission in JIA.
As Dr. Avcin explained, immunological markers such as S100 proteins have shown promise as a biomarker of subclinical active disease.
“Even if a child appears to have clinically inactive disease, elevated levels of these markers may help predict which children will remain in remission after discontinuing treatment and which children may be at an increased risk of a disease flare,” he said.
Rounding off the session, Berit Flatø, MD, PhD, from Norway will present delegates with data from an epidemiological study of long-term outcomes of children with JIA as they move into adulthood.
“Dr. Flatø will present the long-term outcome data from children followed for up to 20 years,” Dr. Avcin said. “Biologics have been in pediatric rheumatology for around 17 years so we will be able to see what is the outcome of children with JIA moving into adulthood with our current treatment protocols.”
In the afternoon, on Friday, pediatric experts will team up with their adult rheumatology colleagues in a “challenges in clinical practice” session to update delegates on life-threatening presentations of rheumatic diseases.
“We will highlight life-threatening presentations that are of particular interest in children, like macrophage activation syndrome and complications of systemic connective tissue diseases and systemic vasculitides like Kawasaki disease and Takayasu’s arteritis,” Dr. Avcin said.
The heterogeneous nature of juvenile idiopathic arthritis (JIA), the use of biologics in childhood rheumatic diseases, and a look at the long-term outcomes for children with JIA are just some of the highlights from the pediatric rheumatology sessions at this year’s EULAR Congress in Madrid, June 14-17.
EULAR Standing Committee Chairperson for Paediatric Rheumatology Tadej Avcin, MD, PhD, said that a bench-to-bedside session on the heterogeneity of JIA on the afternoon of Thursday, June 15, would explore the biologic basis of the disease, the role of cytokine profiling, and the clinical variability in the disease.
“By highlighting the heterogeneity of JIA, we hope this session will contribute to the further understanding of differences between JIA subtypes, as well as contribute some scientific background for the further classification of children with JIA,” he said.
Another “not to miss” session from the pediatric program that will be held on the afternoon of Friday, June 16, is the open issues session on the use of biologic agents in JIA, according to Dr. Avcin, professor of pediatrics and head of the department of allergology, rheumatology, and clinical immunology at University Children’s Hospital, University Medical Center, Ljubljana, Slovenia.
Speaking on the long-term side effects of biologics, Joost Swart, MD, from Utrecht in the Netherlands will present some novel data from the large ongoing pharmacovigilance project Pharmachild that follows children aged 3-10 years who have been treated with methotrexate or a biologic.
At the same session, Pierre Quartier, MD, from Paris will take delegates through data on autoimmune phenomena that can occur in children who are on biologic treatment.
“We know that, in treating children with biologics, they can sometimes develop antidrug antibodies and various induced autoimmune phenomena. We would like to highlight this aspect so that physicians can have more of an overview of possible immune-mediated adverse effects in their patients,” Dr. Avcin said.
The session will also address what Dr. Avcin describes as an emerging and important clinical question: When and how do you discontinue treatment in children with sustained remission?
It’s a question he hopes Gerd Horneff, MD, from Germany will be able to shed some light on when he shares data on how frequently children experience disease flares after discontinuing treatment.
Another pediatric highlight is a morning session on Saturday, June 17, that will address the long-term outcomes of children with JIA.
A presentation by Marion van Rossum, MD, PhD, from the Netherlands will explore whether there are certain clinical or laboratory markers that can help identify children who are more likely to respond well to treatment, compared with other children.
Dirk Foell, MD, from Germany will follow with a session on immunological markers of remission in JIA.
As Dr. Avcin explained, immunological markers such as S100 proteins have shown promise as a biomarker of subclinical active disease.
“Even if a child appears to have clinically inactive disease, elevated levels of these markers may help predict which children will remain in remission after discontinuing treatment and which children may be at an increased risk of a disease flare,” he said.
Rounding off the session, Berit Flatø, MD, PhD, from Norway will present delegates with data from an epidemiological study of long-term outcomes of children with JIA as they move into adulthood.
“Dr. Flatø will present the long-term outcome data from children followed for up to 20 years,” Dr. Avcin said. “Biologics have been in pediatric rheumatology for around 17 years so we will be able to see what is the outcome of children with JIA moving into adulthood with our current treatment protocols.”
In the afternoon, on Friday, pediatric experts will team up with their adult rheumatology colleagues in a “challenges in clinical practice” session to update delegates on life-threatening presentations of rheumatic diseases.
“We will highlight life-threatening presentations that are of particular interest in children, like macrophage activation syndrome and complications of systemic connective tissue diseases and systemic vasculitides like Kawasaki disease and Takayasu’s arteritis,” Dr. Avcin said.
Factors tied to parents’ intent to vaccinate teens for HPV
in a large study, said Kahee A. Mohammed, MD, of Saint Louis (Missouri) University Center for Outcomes Research, and associates.
Messages to boost HPV vaccination rates may need to be targeted based on maternal education, non-Hispanic white ethnicity, and provider recommendations, the researchers said.
Among unvaccinated girls, independent variables predicting parents’ intent to vaccinate teens for HPV were Hispanic race/ethnicity (AOR, 1.57), compared with non-Hispanic whites; mothers with less than a high school diploma (AOR, 1.86), compared with mothers with a college education; and a provider recommendation for HPV vaccine (AOR, 1.38).
Also, mothers with some college education were more likely to intend to vaccinate their sons (AOR, 1.21), but less likely to intend to vaccinate their daughters (AOR, .69) than mothers with a college education.
About 7% of the survey respondents said “not sure/don’t know” regarding their intent to vaccinate their teens. The largest percentage had boys (66%), were non-Hispanic whites (47%), lived in the South (38%), lived above the poverty line (62%), the mother was a college graduate (31%), and had never received a recommendation for HPV vaccination from a health care provider (75%).
“Health care providers should actively engage in discussions with parents about HPV and strongly recommend the vaccine to all eligible patients concurrently with other routinely administered vaccinations to dispel any potential negative assumptions or opinions regarding HPV vaccination, especially among girls,” Dr. Mohammed and his associates said.
Read more at (Prev Chronic Dis. 2017. doi: 10.5888/pcd14.160314).
in a large study, said Kahee A. Mohammed, MD, of Saint Louis (Missouri) University Center for Outcomes Research, and associates.
Messages to boost HPV vaccination rates may need to be targeted based on maternal education, non-Hispanic white ethnicity, and provider recommendations, the researchers said.
Among unvaccinated girls, independent variables predicting parents’ intent to vaccinate teens for HPV were Hispanic race/ethnicity (AOR, 1.57), compared with non-Hispanic whites; mothers with less than a high school diploma (AOR, 1.86), compared with mothers with a college education; and a provider recommendation for HPV vaccine (AOR, 1.38).
Also, mothers with some college education were more likely to intend to vaccinate their sons (AOR, 1.21), but less likely to intend to vaccinate their daughters (AOR, .69) than mothers with a college education.
About 7% of the survey respondents said “not sure/don’t know” regarding their intent to vaccinate their teens. The largest percentage had boys (66%), were non-Hispanic whites (47%), lived in the South (38%), lived above the poverty line (62%), the mother was a college graduate (31%), and had never received a recommendation for HPV vaccination from a health care provider (75%).
“Health care providers should actively engage in discussions with parents about HPV and strongly recommend the vaccine to all eligible patients concurrently with other routinely administered vaccinations to dispel any potential negative assumptions or opinions regarding HPV vaccination, especially among girls,” Dr. Mohammed and his associates said.
Read more at (Prev Chronic Dis. 2017. doi: 10.5888/pcd14.160314).
in a large study, said Kahee A. Mohammed, MD, of Saint Louis (Missouri) University Center for Outcomes Research, and associates.
Messages to boost HPV vaccination rates may need to be targeted based on maternal education, non-Hispanic white ethnicity, and provider recommendations, the researchers said.
Among unvaccinated girls, independent variables predicting parents’ intent to vaccinate teens for HPV were Hispanic race/ethnicity (AOR, 1.57), compared with non-Hispanic whites; mothers with less than a high school diploma (AOR, 1.86), compared with mothers with a college education; and a provider recommendation for HPV vaccine (AOR, 1.38).
Also, mothers with some college education were more likely to intend to vaccinate their sons (AOR, 1.21), but less likely to intend to vaccinate their daughters (AOR, .69) than mothers with a college education.
About 7% of the survey respondents said “not sure/don’t know” regarding their intent to vaccinate their teens. The largest percentage had boys (66%), were non-Hispanic whites (47%), lived in the South (38%), lived above the poverty line (62%), the mother was a college graduate (31%), and had never received a recommendation for HPV vaccination from a health care provider (75%).
“Health care providers should actively engage in discussions with parents about HPV and strongly recommend the vaccine to all eligible patients concurrently with other routinely administered vaccinations to dispel any potential negative assumptions or opinions regarding HPV vaccination, especially among girls,” Dr. Mohammed and his associates said.
Read more at (Prev Chronic Dis. 2017. doi: 10.5888/pcd14.160314).
FROM PREVENTING CHRONIC DISEASE
It matters how you phrase a child’s flu vaccine recommendation
Vaccine hesitant parents were more likely to change their minds about flu vaccine for their children when pediatricians or pediatric nurse practitioners used a presumptive recommendation that their children get the vaccine, pursued the recommendation if the parent was resistant, and combined their recommendation for the flu vaccine with other childhood vaccines, said Annika M. Hofstetter, MD, PhD, of the University of Washington, Seattle, and her associates.
The researchers recruited 17 pediatricians and pediatric nurse practitioners from eight primary care pediatric practices in the Seattle area to take part in 50 videotaped visits with parents during the 2011-2012 and 2013-2014 flu seasons.
(83% vs. 33%; P less than .01), Dr. Hofstetter and her colleagues said. The various communication patterns did not appear to negatively affect the way parents rated their visit experiences.
Read more at Vaccine. 2017;35:2709-15.
Vaccine hesitant parents were more likely to change their minds about flu vaccine for their children when pediatricians or pediatric nurse practitioners used a presumptive recommendation that their children get the vaccine, pursued the recommendation if the parent was resistant, and combined their recommendation for the flu vaccine with other childhood vaccines, said Annika M. Hofstetter, MD, PhD, of the University of Washington, Seattle, and her associates.
The researchers recruited 17 pediatricians and pediatric nurse practitioners from eight primary care pediatric practices in the Seattle area to take part in 50 videotaped visits with parents during the 2011-2012 and 2013-2014 flu seasons.
(83% vs. 33%; P less than .01), Dr. Hofstetter and her colleagues said. The various communication patterns did not appear to negatively affect the way parents rated their visit experiences.
Read more at Vaccine. 2017;35:2709-15.
Vaccine hesitant parents were more likely to change their minds about flu vaccine for their children when pediatricians or pediatric nurse practitioners used a presumptive recommendation that their children get the vaccine, pursued the recommendation if the parent was resistant, and combined their recommendation for the flu vaccine with other childhood vaccines, said Annika M. Hofstetter, MD, PhD, of the University of Washington, Seattle, and her associates.
The researchers recruited 17 pediatricians and pediatric nurse practitioners from eight primary care pediatric practices in the Seattle area to take part in 50 videotaped visits with parents during the 2011-2012 and 2013-2014 flu seasons.
(83% vs. 33%; P less than .01), Dr. Hofstetter and her colleagues said. The various communication patterns did not appear to negatively affect the way parents rated their visit experiences.
Read more at Vaccine. 2017;35:2709-15.
FROM VACCINE
Everything We Say and Do: Setting discharge goals and visit expectations
Editor’s note: “Everything We Say and Do” is an informational series developed by SHM’s Patient Experience Committee to provide readers with thoughtful and actionable communication tactics that have great potential to positively impact patients’ experience of care. Each article will focus on how the contributor applies one or more of the “key communication” tactics in practice to maintain provider accountability for “everything we say and do that affects our patients’ thoughts, feelings, and well-being.”
What I say and do
I always ensure at the end of my visit with a patient and their family that they know when to expect me to return to see their child again.
Why I do it
One of the biggest frustrations I hear from families pertains to the discharge process. In talking with families, they want to know the approximate time for discharge. Often, during morning rounds, we mention that the patient may be able to go home later in the day and we say that we will come in again later to check on them. However, unless we give families a time frame for when we will come back and do that check, they are left waiting without any clear expectations.
How I do it
One of our goals during morning family-centered rounds is to discuss discharge for every patient, every day. Along with discussing the possibility of going home, we try to give the family goals that they can work on throughout the day that are tied to discharge – for example, the approximate by-mouth intake for a toddler admitted for gastroenteritis and dehydration.
I also give the family an approximate time when either I or the resident team will come back to see if they have achieved this goal. This may be either late afternoon or first thing in the morning if we are planning an early-morning discharge before rounds. The families seem to find this helpful because they are not tied to the room all day waiting for the doctor to come back.
I also make sure that the families know they can contact their nurse any time if they need to see any of the doctors sooner than we planned. I let them know that a physician is here on the floor 24 hours a day and that the nurses can easily reach us at any time if they have further concerns. In my experience, this is reassuring to our families.
Christine Hrach is a pediatric hospitalist at Washington University School of Medicine in St. Louis.
Editor’s note: “Everything We Say and Do” is an informational series developed by SHM’s Patient Experience Committee to provide readers with thoughtful and actionable communication tactics that have great potential to positively impact patients’ experience of care. Each article will focus on how the contributor applies one or more of the “key communication” tactics in practice to maintain provider accountability for “everything we say and do that affects our patients’ thoughts, feelings, and well-being.”
What I say and do
I always ensure at the end of my visit with a patient and their family that they know when to expect me to return to see their child again.
Why I do it
One of the biggest frustrations I hear from families pertains to the discharge process. In talking with families, they want to know the approximate time for discharge. Often, during morning rounds, we mention that the patient may be able to go home later in the day and we say that we will come in again later to check on them. However, unless we give families a time frame for when we will come back and do that check, they are left waiting without any clear expectations.
How I do it
One of our goals during morning family-centered rounds is to discuss discharge for every patient, every day. Along with discussing the possibility of going home, we try to give the family goals that they can work on throughout the day that are tied to discharge – for example, the approximate by-mouth intake for a toddler admitted for gastroenteritis and dehydration.
I also give the family an approximate time when either I or the resident team will come back to see if they have achieved this goal. This may be either late afternoon or first thing in the morning if we are planning an early-morning discharge before rounds. The families seem to find this helpful because they are not tied to the room all day waiting for the doctor to come back.
I also make sure that the families know they can contact their nurse any time if they need to see any of the doctors sooner than we planned. I let them know that a physician is here on the floor 24 hours a day and that the nurses can easily reach us at any time if they have further concerns. In my experience, this is reassuring to our families.
Christine Hrach is a pediatric hospitalist at Washington University School of Medicine in St. Louis.
Editor’s note: “Everything We Say and Do” is an informational series developed by SHM’s Patient Experience Committee to provide readers with thoughtful and actionable communication tactics that have great potential to positively impact patients’ experience of care. Each article will focus on how the contributor applies one or more of the “key communication” tactics in practice to maintain provider accountability for “everything we say and do that affects our patients’ thoughts, feelings, and well-being.”
What I say and do
I always ensure at the end of my visit with a patient and their family that they know when to expect me to return to see their child again.
Why I do it
One of the biggest frustrations I hear from families pertains to the discharge process. In talking with families, they want to know the approximate time for discharge. Often, during morning rounds, we mention that the patient may be able to go home later in the day and we say that we will come in again later to check on them. However, unless we give families a time frame for when we will come back and do that check, they are left waiting without any clear expectations.
How I do it
One of our goals during morning family-centered rounds is to discuss discharge for every patient, every day. Along with discussing the possibility of going home, we try to give the family goals that they can work on throughout the day that are tied to discharge – for example, the approximate by-mouth intake for a toddler admitted for gastroenteritis and dehydration.
I also give the family an approximate time when either I or the resident team will come back to see if they have achieved this goal. This may be either late afternoon or first thing in the morning if we are planning an early-morning discharge before rounds. The families seem to find this helpful because they are not tied to the room all day waiting for the doctor to come back.
I also make sure that the families know they can contact their nurse any time if they need to see any of the doctors sooner than we planned. I let them know that a physician is here on the floor 24 hours a day and that the nurses can easily reach us at any time if they have further concerns. In my experience, this is reassuring to our families.
Christine Hrach is a pediatric hospitalist at Washington University School of Medicine in St. Louis.
Pembrolizumab enhances CAR T-cell persistence in relapsed ALL
CHICAGO—Three of 6 pediatric patients with relapsed or refractory acute lymphoblastic leukemia (ALL) whose CD19 chimeric antigen receptor (CAR) T cells did not persist even after reinfusion demonstrated persistence when the PD-1 checkpoint inhibitor pembrolizumab was added to the regimen.
CAR T cells can persist for months or even years and have the potential to mediate long-term disease control.
But some patients recover their normal B cells, which is a marker of loss of functional CAR T cells. These patients are at a higher risk of disease relapse.
Investigators, therefore, undertook a pilot study to determine whether PD-1 checkpoint pathway inhibition can improve CAR T persistence in these patients.
Shannon L. Maude, MD, of the Children’s Hospital of Philadelphia and the University of Pennsylvania Perelman School of Medicine, shared some of the patient cases in this pilot study at the ASCO 2017 Annual Meeting (Abstract 103*).
The investigators hypothesized that possible anti-murine immunogenicity could be causing poor CAR T-cell persistence, since the first CAR T developed used scFv domains of murine origin.
If T-cell exhaustion caused poor CAR T-cell persistence, immune checkpoints might play a role. In this case, combination with PD-1 checkpoint blockade could improve persistence, they hypothesized.
The investigators proposed to administer a repeat CAR T-cell infusion for relapsed or refractory ALL patients with poor persistence and add pembrolizumab after retreatment if the patients still had poor persistence. Patients were offered the option of another reinfusion prior to treatment with pembrolizumab if their CAR T-cell persistence continued to be poor.
Investigators added pembrolizumab no earlier than 14 days after infusion and only after patients recovered from cytokine release syndrome (CRS).
The infusions in the pilot study were humanized CART19 (huCART19, CTL119), unless otherwise specified.
Patient 1 – Pembrolizumab for partial response
This patient had no response to the prior murine CD19 CAR infusion, but responded well to infusion with huCART19 with good CAR T-cell proliferation.
By day 28, the patient had achieved a complete response (CR) in bone marrow but had a minimal residual disease (MRD) level of 1.2%.
At 7 weeks, the patient had a CD19+ relapse with low levels of huCART19.
Investigators added pembrolizumb on day 52 after infusion, and the patient had a modest increase in huCART19.
The patient had a temporary clearance of peripheral blasts followed by disease progression.
Patient 2 – Pembrolizumab for no response
This patient had a CD19+ relapse at 12 months after prior murine CD19 CAR infusion.
The patient was treated with huCART19, had good proliferation, but a rapid drop of CART19, and no response of the disease with a CD19+ relapse.
The patient had a reinfusion of huCART19 at 6 weeks and investigators added pembrolizumab on day 14 after reinfusion.
The patient experienced good huCART19 proliferation and prolonged persistence, but by day 28 had persistent disease, this time with decreased expression of CD19+ cells.
Patient 3 – Pembrolizumab for poor persistence
This patient had a CR with a prior murine CD19 CAR, but had poor persistence and early B cell recovery at 2 months.
The patient had a CD19+ relapse, was treated with huCART19, and had good proliferation again.
The patient achieved an MRD-negative CR, but because of short persistence and early B-cell recovery at 2 months, relapsed at 15 months.
The patient was reinfused at 17 months and pembrolizumab was added on day 14. The patient entered CR with prolonged persistence, but ultimately B-cell recovery occurred.
The patient was reinfused a third time, and pembrolizumab was added to the regimen every 3 weeks. The patient is experiencing prolonged persistence and continued B-cell aplasia.
Patient 4 – Pembrolizumab for poor persistence
This patient had achieved a CR with murine CAR19, but had a CD19+ relapse at 9 months. The patient then received huCART19, had good proliferation and achieved a CR, but had short persistence and B-cell recovery at 2 months.
The patient relapsed at 12 months and was reinfused with huCART19 at 14 months.
Pembrolizumab was added on day 14 after reinfusion, but the patient had no huCART19 proliferation, no response, and CD19+ MRD.
Patient 5 – Pembrolizumab for poor persistence
The patient responded to a prior murine CART19, but had a CD19+ relapse at 12 months.
The patient was infused with huCART19 and had good proliferation but short persistence. The patient was reinfused at 6 months, but again had short persistence.
The patient was reinfused again at 8 months because of B-cell recovery, and pembrolizumab was added on day 14 and administered every 3 weeks thereafter.
The patient is experiencing prolonged persistence and continued B-cell aplasia.
Patient 6 – Pembrolizumab for lymphomatous disease
This patient, who had widespread lymphadenopathy and M3 bone marrow, had not received prior CAR T cells and was treated for the first time with a murine CART19 for r/r ALL.
The patient had good expansion of CART19, but by day 28, PET scan showed widespread lymph node disease despite CR in the bone marrow.
The patient was given pembrolizumab on day 32 after infusion and every 2-3 weeks thereafter. After the addition of pembrolizumab, the patient had increased CART19 cells in blood and a significant decrease in PET-avid disease.
Summary
Three of six patients achieved objective clinical responses with pembrolizumab: 2 had prolonged B-cell aplasia, and another had a decrease in PET-avid lymphomatous disease.
The addition of pembrolizumab was also well tolerated by the patients, with minimal side effects of fever in 2 patients, cytopenias in 2 patients, and no instances of severe CRS.
The investigators believe the addition of checkpoint pathway inhibitors has the potential to prolong CAR T-cell persistence and warrants further investigation. 
CHICAGO—Three of 6 pediatric patients with relapsed or refractory acute lymphoblastic leukemia (ALL) whose CD19 chimeric antigen receptor (CAR) T cells did not persist even after reinfusion demonstrated persistence when the PD-1 checkpoint inhibitor pembrolizumab was added to the regimen.
CAR T cells can persist for months or even years and have the potential to mediate long-term disease control.
But some patients recover their normal B cells, which is a marker of loss of functional CAR T cells. These patients are at a higher risk of disease relapse.
Investigators, therefore, undertook a pilot study to determine whether PD-1 checkpoint pathway inhibition can improve CAR T persistence in these patients.
Shannon L. Maude, MD, of the Children’s Hospital of Philadelphia and the University of Pennsylvania Perelman School of Medicine, shared some of the patient cases in this pilot study at the ASCO 2017 Annual Meeting (Abstract 103*).
The investigators hypothesized that possible anti-murine immunogenicity could be causing poor CAR T-cell persistence, since the first CAR T developed used scFv domains of murine origin.
If T-cell exhaustion caused poor CAR T-cell persistence, immune checkpoints might play a role. In this case, combination with PD-1 checkpoint blockade could improve persistence, they hypothesized.
The investigators proposed to administer a repeat CAR T-cell infusion for relapsed or refractory ALL patients with poor persistence and add pembrolizumab after retreatment if the patients still had poor persistence. Patients were offered the option of another reinfusion prior to treatment with pembrolizumab if their CAR T-cell persistence continued to be poor.
Investigators added pembrolizumab no earlier than 14 days after infusion and only after patients recovered from cytokine release syndrome (CRS).
The infusions in the pilot study were humanized CART19 (huCART19, CTL119), unless otherwise specified.
Patient 1 – Pembrolizumab for partial response
This patient had no response to the prior murine CD19 CAR infusion, but responded well to infusion with huCART19 with good CAR T-cell proliferation.
By day 28, the patient had achieved a complete response (CR) in bone marrow but had a minimal residual disease (MRD) level of 1.2%.
At 7 weeks, the patient had a CD19+ relapse with low levels of huCART19.
Investigators added pembrolizumb on day 52 after infusion, and the patient had a modest increase in huCART19.
The patient had a temporary clearance of peripheral blasts followed by disease progression.
Patient 2 – Pembrolizumab for no response
This patient had a CD19+ relapse at 12 months after prior murine CD19 CAR infusion.
The patient was treated with huCART19, had good proliferation, but a rapid drop of CART19, and no response of the disease with a CD19+ relapse.
The patient had a reinfusion of huCART19 at 6 weeks and investigators added pembrolizumab on day 14 after reinfusion.
The patient experienced good huCART19 proliferation and prolonged persistence, but by day 28 had persistent disease, this time with decreased expression of CD19+ cells.
Patient 3 – Pembrolizumab for poor persistence
This patient had a CR with a prior murine CD19 CAR, but had poor persistence and early B cell recovery at 2 months.
The patient had a CD19+ relapse, was treated with huCART19, and had good proliferation again.
The patient achieved an MRD-negative CR, but because of short persistence and early B-cell recovery at 2 months, relapsed at 15 months.
The patient was reinfused at 17 months and pembrolizumab was added on day 14. The patient entered CR with prolonged persistence, but ultimately B-cell recovery occurred.
The patient was reinfused a third time, and pembrolizumab was added to the regimen every 3 weeks. The patient is experiencing prolonged persistence and continued B-cell aplasia.
Patient 4 – Pembrolizumab for poor persistence
This patient had achieved a CR with murine CAR19, but had a CD19+ relapse at 9 months. The patient then received huCART19, had good proliferation and achieved a CR, but had short persistence and B-cell recovery at 2 months.
The patient relapsed at 12 months and was reinfused with huCART19 at 14 months.
Pembrolizumab was added on day 14 after reinfusion, but the patient had no huCART19 proliferation, no response, and CD19+ MRD.
Patient 5 – Pembrolizumab for poor persistence
The patient responded to a prior murine CART19, but had a CD19+ relapse at 12 months.
The patient was infused with huCART19 and had good proliferation but short persistence. The patient was reinfused at 6 months, but again had short persistence.
The patient was reinfused again at 8 months because of B-cell recovery, and pembrolizumab was added on day 14 and administered every 3 weeks thereafter.
The patient is experiencing prolonged persistence and continued B-cell aplasia.
Patient 6 – Pembrolizumab for lymphomatous disease
This patient, who had widespread lymphadenopathy and M3 bone marrow, had not received prior CAR T cells and was treated for the first time with a murine CART19 for r/r ALL.
The patient had good expansion of CART19, but by day 28, PET scan showed widespread lymph node disease despite CR in the bone marrow.
The patient was given pembrolizumab on day 32 after infusion and every 2-3 weeks thereafter. After the addition of pembrolizumab, the patient had increased CART19 cells in blood and a significant decrease in PET-avid disease.
Summary
Three of six patients achieved objective clinical responses with pembrolizumab: 2 had prolonged B-cell aplasia, and another had a decrease in PET-avid lymphomatous disease.
The addition of pembrolizumab was also well tolerated by the patients, with minimal side effects of fever in 2 patients, cytopenias in 2 patients, and no instances of severe CRS.
The investigators believe the addition of checkpoint pathway inhibitors has the potential to prolong CAR T-cell persistence and warrants further investigation.
CHICAGO—Three of 6 pediatric patients with relapsed or refractory acute lymphoblastic leukemia (ALL) whose CD19 chimeric antigen receptor (CAR) T cells did not persist even after reinfusion demonstrated persistence when the PD-1 checkpoint inhibitor pembrolizumab was added to the regimen.
CAR T cells can persist for months or even years and have the potential to mediate long-term disease control.
But some patients recover their normal B cells, which is a marker of loss of functional CAR T cells. These patients are at a higher risk of disease relapse.
Investigators, therefore, undertook a pilot study to determine whether PD-1 checkpoint pathway inhibition can improve CAR T persistence in these patients.
Shannon L. Maude, MD, of the Children’s Hospital of Philadelphia and the University of Pennsylvania Perelman School of Medicine, shared some of the patient cases in this pilot study at the ASCO 2017 Annual Meeting (Abstract 103*).
The investigators hypothesized that possible anti-murine immunogenicity could be causing poor CAR T-cell persistence, since the first CAR T developed used scFv domains of murine origin.
If T-cell exhaustion caused poor CAR T-cell persistence, immune checkpoints might play a role. In this case, combination with PD-1 checkpoint blockade could improve persistence, they hypothesized.
The investigators proposed to administer a repeat CAR T-cell infusion for relapsed or refractory ALL patients with poor persistence and add pembrolizumab after retreatment if the patients still had poor persistence. Patients were offered the option of another reinfusion prior to treatment with pembrolizumab if their CAR T-cell persistence continued to be poor.
Investigators added pembrolizumab no earlier than 14 days after infusion and only after patients recovered from cytokine release syndrome (CRS).
The infusions in the pilot study were humanized CART19 (huCART19, CTL119), unless otherwise specified.
Patient 1 – Pembrolizumab for partial response
This patient had no response to the prior murine CD19 CAR infusion, but responded well to infusion with huCART19 with good CAR T-cell proliferation.
By day 28, the patient had achieved a complete response (CR) in bone marrow but had a minimal residual disease (MRD) level of 1.2%.
At 7 weeks, the patient had a CD19+ relapse with low levels of huCART19.
Investigators added pembrolizumb on day 52 after infusion, and the patient had a modest increase in huCART19.
The patient had a temporary clearance of peripheral blasts followed by disease progression.
Patient 2 – Pembrolizumab for no response
This patient had a CD19+ relapse at 12 months after prior murine CD19 CAR infusion.
The patient was treated with huCART19, had good proliferation, but a rapid drop of CART19, and no response of the disease with a CD19+ relapse.
The patient had a reinfusion of huCART19 at 6 weeks and investigators added pembrolizumab on day 14 after reinfusion.
The patient experienced good huCART19 proliferation and prolonged persistence, but by day 28 had persistent disease, this time with decreased expression of CD19+ cells.
Patient 3 – Pembrolizumab for poor persistence
This patient had a CR with a prior murine CD19 CAR, but had poor persistence and early B cell recovery at 2 months.
The patient had a CD19+ relapse, was treated with huCART19, and had good proliferation again.
The patient achieved an MRD-negative CR, but because of short persistence and early B-cell recovery at 2 months, relapsed at 15 months.
The patient was reinfused at 17 months and pembrolizumab was added on day 14. The patient entered CR with prolonged persistence, but ultimately B-cell recovery occurred.
The patient was reinfused a third time, and pembrolizumab was added to the regimen every 3 weeks. The patient is experiencing prolonged persistence and continued B-cell aplasia.
Patient 4 – Pembrolizumab for poor persistence
This patient had achieved a CR with murine CAR19, but had a CD19+ relapse at 9 months. The patient then received huCART19, had good proliferation and achieved a CR, but had short persistence and B-cell recovery at 2 months.
The patient relapsed at 12 months and was reinfused with huCART19 at 14 months.
Pembrolizumab was added on day 14 after reinfusion, but the patient had no huCART19 proliferation, no response, and CD19+ MRD.
Patient 5 – Pembrolizumab for poor persistence
The patient responded to a prior murine CART19, but had a CD19+ relapse at 12 months.
The patient was infused with huCART19 and had good proliferation but short persistence. The patient was reinfused at 6 months, but again had short persistence.
The patient was reinfused again at 8 months because of B-cell recovery, and pembrolizumab was added on day 14 and administered every 3 weeks thereafter.
The patient is experiencing prolonged persistence and continued B-cell aplasia.
Patient 6 – Pembrolizumab for lymphomatous disease
This patient, who had widespread lymphadenopathy and M3 bone marrow, had not received prior CAR T cells and was treated for the first time with a murine CART19 for r/r ALL.
The patient had good expansion of CART19, but by day 28, PET scan showed widespread lymph node disease despite CR in the bone marrow.
The patient was given pembrolizumab on day 32 after infusion and every 2-3 weeks thereafter. After the addition of pembrolizumab, the patient had increased CART19 cells in blood and a significant decrease in PET-avid disease.
Summary
Three of six patients achieved objective clinical responses with pembrolizumab: 2 had prolonged B-cell aplasia, and another had a decrease in PET-avid lymphomatous disease.
The addition of pembrolizumab was also well tolerated by the patients, with minimal side effects of fever in 2 patients, cytopenias in 2 patients, and no instances of severe CRS.
The investigators believe the addition of checkpoint pathway inhibitors has the potential to prolong CAR T-cell persistence and warrants further investigation.
Management of asymptomatic chorioamnionitis-exposed neonates needs revamping
Clinical observation and laboratory evaluation without immediate antibiotic use in asymptomatic chorioamnionitis-exposed neonates prevented neonatal intensive care unit (NICU) admission in two-thirds of these infants, Amanda I. Jan, MD, of the University of Southern California, Los Angeles, and her associates reported in a study.
Since maternal intrapartum antibiotic prophylaxis was introduced, neonatal early-onset sepsis (EOS) rates have dropped considerably, and rates remain low even in chorioamnionitis-exposed infants. Despite these low risks, current American Academy of Pediatrics and Centers for Disease Control and Prevention recommendations still call for a limited laboratory evaluation and immediate empirical antibiotic therapy in all infants exposed to chorioamnionitis, often necessitating NICU admission for IV antibiotics, the researchers noted.
Of the 78 infants admitted to the NICU and put on antibiotics, 76% were treated with antibiotics for more than 72 hours, with a median 7 days of treatment, compared with a median 2 days for nonadmitted infants (P less than .001). Only 85% of admitted infants received any breast milk, compared with 94% of infants in the mother-infant unit (P = .032), and none of the admitted infants were exclusively breastfed.
“When the overall risks of EOS are low, exposure of large numbers of well-appearing infants to even short courses of antibiotics is no longer justified,” Dr. Jan and her associates stated. “The [difference in] cost of a stay in the mother-infant unit for 2 days, compared with a NICU stay, which averaged a week, is substantial. The charge for our NICU is $12,612 per day in contrast to $5,300 per day in the mother-infant unit. The cost savings for the 162 infants who were cared for 2 days in the mother-infant unit, compared with an EOS evaluation and antibiotic therapy in the NICU, totals $2,369,088, or $359,861 per year.
“There were no deaths or morbidities identified in any infant during the study period,” they reported. No infant was readmitted to the study hospital for sepsis after discharge.
Dr. Jan and her associates recommend their alternative management of asymptomatic chorioamnionitis-exposed neonates involving lab evaluations and close clinical observation without immediate antibiotic administration in a mother-infant unit. They believe this prevents unnecessary antibiotic exposure, unnecessarily high hospitalization costs, and disruption of maternal-neonatal bonding and breastfeeding. Additional studies are needed to determine the safety of this approach.
This study received no external funding, and Dr. Jan and her associates reported no relevant financial disclosures.
Dr. Jan and her associates have taken steps in the right direction in altering management of asymptomatic term and near-term newborns with a maternal history of chorioamnionitis to avoid administering empirical antibiotics to all these babies, which is sorely needed as the current American Academy of Pediatrics and Centers for Disease Control and Prevention guidelines are outdated.
However, their alternative plan needs some tweaking. The positive predictive value of abnormal complete blood count or C-reactive protein results is too low to be of use in diagnosing sepsis. “We believe a better approach would be to forgo routine laboratory evaluations among this population altogether and manage them using clinical signs alone.”
They said it was important to state two key caveats. “First, in the immediate postpartum period, mild respiratory distress among term or near-term newborns may be attributable to the physiologic transition, which occurs in all newborn infants. It is not necessary to draw laboratories or start antibiotics on these patients as long as their symptoms improve and resolve within the first 6 hours of life. Second, if newborns with a maternal history of chorioamnionitis are to be monitored for signs of sepsis outside the NICU setting, observations must be frequent (at least hourly for the first 6 hours of life and then every 3 hours for the next 18 hours) and performed by adequately trained medical staff. In the absence of frequent, reliable observation, there is a possibility that the early signs of sepsis will be missed and go untreated with potentially severe consequences.”
This approach, as with any other, needs additional study.
Thomas A. Hooven, MD, and Richard A. Polin, MD, pediatricians at the Columbia University, New York, discussed the study by Jan et al. in a commentary, which is summarized here (Pediatrics. 2017;140[1]:e20171155). They reported that they received no external funding and had no relevant financial disclosures.
Dr. Jan and her associates have taken steps in the right direction in altering management of asymptomatic term and near-term newborns with a maternal history of chorioamnionitis to avoid administering empirical antibiotics to all these babies, which is sorely needed as the current American Academy of Pediatrics and Centers for Disease Control and Prevention guidelines are outdated.
However, their alternative plan needs some tweaking. The positive predictive value of abnormal complete blood count or C-reactive protein results is too low to be of use in diagnosing sepsis. “We believe a better approach would be to forgo routine laboratory evaluations among this population altogether and manage them using clinical signs alone.”
They said it was important to state two key caveats. “First, in the immediate postpartum period, mild respiratory distress among term or near-term newborns may be attributable to the physiologic transition, which occurs in all newborn infants. It is not necessary to draw laboratories or start antibiotics on these patients as long as their symptoms improve and resolve within the first 6 hours of life. Second, if newborns with a maternal history of chorioamnionitis are to be monitored for signs of sepsis outside the NICU setting, observations must be frequent (at least hourly for the first 6 hours of life and then every 3 hours for the next 18 hours) and performed by adequately trained medical staff. In the absence of frequent, reliable observation, there is a possibility that the early signs of sepsis will be missed and go untreated with potentially severe consequences.”
This approach, as with any other, needs additional study.
Thomas A. Hooven, MD, and Richard A. Polin, MD, pediatricians at the Columbia University, New York, discussed the study by Jan et al. in a commentary, which is summarized here (Pediatrics. 2017;140[1]:e20171155). They reported that they received no external funding and had no relevant financial disclosures.
Dr. Jan and her associates have taken steps in the right direction in altering management of asymptomatic term and near-term newborns with a maternal history of chorioamnionitis to avoid administering empirical antibiotics to all these babies, which is sorely needed as the current American Academy of Pediatrics and Centers for Disease Control and Prevention guidelines are outdated.
However, their alternative plan needs some tweaking. The positive predictive value of abnormal complete blood count or C-reactive protein results is too low to be of use in diagnosing sepsis. “We believe a better approach would be to forgo routine laboratory evaluations among this population altogether and manage them using clinical signs alone.”
They said it was important to state two key caveats. “First, in the immediate postpartum period, mild respiratory distress among term or near-term newborns may be attributable to the physiologic transition, which occurs in all newborn infants. It is not necessary to draw laboratories or start antibiotics on these patients as long as their symptoms improve and resolve within the first 6 hours of life. Second, if newborns with a maternal history of chorioamnionitis are to be monitored for signs of sepsis outside the NICU setting, observations must be frequent (at least hourly for the first 6 hours of life and then every 3 hours for the next 18 hours) and performed by adequately trained medical staff. In the absence of frequent, reliable observation, there is a possibility that the early signs of sepsis will be missed and go untreated with potentially severe consequences.”
This approach, as with any other, needs additional study.
Thomas A. Hooven, MD, and Richard A. Polin, MD, pediatricians at the Columbia University, New York, discussed the study by Jan et al. in a commentary, which is summarized here (Pediatrics. 2017;140[1]:e20171155). They reported that they received no external funding and had no relevant financial disclosures.
Clinical observation and laboratory evaluation without immediate antibiotic use in asymptomatic chorioamnionitis-exposed neonates prevented neonatal intensive care unit (NICU) admission in two-thirds of these infants, Amanda I. Jan, MD, of the University of Southern California, Los Angeles, and her associates reported in a study.
Since maternal intrapartum antibiotic prophylaxis was introduced, neonatal early-onset sepsis (EOS) rates have dropped considerably, and rates remain low even in chorioamnionitis-exposed infants. Despite these low risks, current American Academy of Pediatrics and Centers for Disease Control and Prevention recommendations still call for a limited laboratory evaluation and immediate empirical antibiotic therapy in all infants exposed to chorioamnionitis, often necessitating NICU admission for IV antibiotics, the researchers noted.
Of the 78 infants admitted to the NICU and put on antibiotics, 76% were treated with antibiotics for more than 72 hours, with a median 7 days of treatment, compared with a median 2 days for nonadmitted infants (P less than .001). Only 85% of admitted infants received any breast milk, compared with 94% of infants in the mother-infant unit (P = .032), and none of the admitted infants were exclusively breastfed.
“When the overall risks of EOS are low, exposure of large numbers of well-appearing infants to even short courses of antibiotics is no longer justified,” Dr. Jan and her associates stated. “The [difference in] cost of a stay in the mother-infant unit for 2 days, compared with a NICU stay, which averaged a week, is substantial. The charge for our NICU is $12,612 per day in contrast to $5,300 per day in the mother-infant unit. The cost savings for the 162 infants who were cared for 2 days in the mother-infant unit, compared with an EOS evaluation and antibiotic therapy in the NICU, totals $2,369,088, or $359,861 per year.
“There were no deaths or morbidities identified in any infant during the study period,” they reported. No infant was readmitted to the study hospital for sepsis after discharge.
Dr. Jan and her associates recommend their alternative management of asymptomatic chorioamnionitis-exposed neonates involving lab evaluations and close clinical observation without immediate antibiotic administration in a mother-infant unit. They believe this prevents unnecessary antibiotic exposure, unnecessarily high hospitalization costs, and disruption of maternal-neonatal bonding and breastfeeding. Additional studies are needed to determine the safety of this approach.
This study received no external funding, and Dr. Jan and her associates reported no relevant financial disclosures.
Clinical observation and laboratory evaluation without immediate antibiotic use in asymptomatic chorioamnionitis-exposed neonates prevented neonatal intensive care unit (NICU) admission in two-thirds of these infants, Amanda I. Jan, MD, of the University of Southern California, Los Angeles, and her associates reported in a study.
Since maternal intrapartum antibiotic prophylaxis was introduced, neonatal early-onset sepsis (EOS) rates have dropped considerably, and rates remain low even in chorioamnionitis-exposed infants. Despite these low risks, current American Academy of Pediatrics and Centers for Disease Control and Prevention recommendations still call for a limited laboratory evaluation and immediate empirical antibiotic therapy in all infants exposed to chorioamnionitis, often necessitating NICU admission for IV antibiotics, the researchers noted.
Of the 78 infants admitted to the NICU and put on antibiotics, 76% were treated with antibiotics for more than 72 hours, with a median 7 days of treatment, compared with a median 2 days for nonadmitted infants (P less than .001). Only 85% of admitted infants received any breast milk, compared with 94% of infants in the mother-infant unit (P = .032), and none of the admitted infants were exclusively breastfed.
“When the overall risks of EOS are low, exposure of large numbers of well-appearing infants to even short courses of antibiotics is no longer justified,” Dr. Jan and her associates stated. “The [difference in] cost of a stay in the mother-infant unit for 2 days, compared with a NICU stay, which averaged a week, is substantial. The charge for our NICU is $12,612 per day in contrast to $5,300 per day in the mother-infant unit. The cost savings for the 162 infants who were cared for 2 days in the mother-infant unit, compared with an EOS evaluation and antibiotic therapy in the NICU, totals $2,369,088, or $359,861 per year.
“There were no deaths or morbidities identified in any infant during the study period,” they reported. No infant was readmitted to the study hospital for sepsis after discharge.
Dr. Jan and her associates recommend their alternative management of asymptomatic chorioamnionitis-exposed neonates involving lab evaluations and close clinical observation without immediate antibiotic administration in a mother-infant unit. They believe this prevents unnecessary antibiotic exposure, unnecessarily high hospitalization costs, and disruption of maternal-neonatal bonding and breastfeeding. Additional studies are needed to determine the safety of this approach.
This study received no external funding, and Dr. Jan and her associates reported no relevant financial disclosures.
FROM PEDIATRICS
Key clinical point: Alternative management of asymptomatic chorioamnionitis-exposed neonates will prevent unnecessary antibiotic exposure, unnecessarily high hospitalization costs, and disruption of maternal-neonatal bonding and breastfeeding.
Major finding: Of the 240 infants, 67.5% remained well with a routine newborn course in the mother-infant unit and 32.5% subsequently were admitted to the NICU because of abnormal laboratory data, a positive blood culture, or the onset of clinical signs of sepsis.
Data source: A retrospective cohort study of 240 asymptomatic chorioamnionitis-exposed neonates.
Disclosures: This study received no external funding, and Dr. Jan and her associates reported no relevant financial disclosures.
First trimester lithium exposure ups risk of cardiac malformations
Cardiac malformations are three times more likely to occur in infants exposed to lithium during the first trimester of gestation than in unexposed infants.
The increased risk could account for one additional cardiac malformation per 100 live births, Elisabetta Patorno, MD, and her colleagues wrote in the June 8 issue of the New England Journal of Medicine (2017;376:2245-54).
Dr. Patorno’s study is the largest conducted since then. It comprised more than 1.3 million pregnancies included in the U.S. Medicaid Analytic eXtract database during 2000-2010. Of these, 663 had first trimester lithium exposure. These were compared with 1,945 pregnancies with first trimester exposure to lamotrigine, another mood stabilizer, and to the remaining 1.3 million pregnancies unexposed to either drug.
There were 16 cardiac malformations in the lithium group (2.41%); 27 in the lamotrigine group (1.39%); and 15,251 in the unexposed group (1.15%). Lithium conferred a 65% increased risk of cardiac defect, compared with unexposed pregnancies. It more than doubled the risk when compared with lamotrigine-exposed pregnancies (risk ratio, 2.25).
The risk was dose dependent, however, with an 11% increase associated with 600 mg/day or less and a 60% increase associated with 601-900 mg/day. Infants exposed to more than 900 mg per day in the first trimester, however, were more than 300% more likely to have a cardiac malformation (RR, 3.22).
The investigators also examined the association of lithium with cardiac defects consistent with Ebstein’s anomaly. Lithium more than doubled the risk, compared with unexposed infants (RR, 2.66). This risk was also dose dependent; all of the right ventricular outflow defects occurred in infants exposed to more than 600 mg/day.
Dr. Patorno reported grant support from National Institute of Mental Health during the study and grant support from Boehringer Ingelheim and GlaxoSmithKline outside of the study. Other authors reported receiving grants or personal fees from various pharmaceutical companies.
msullivan@frontlinemedcom.com
On Twitter @Alz_gal
Cardiac malformations are three times more likely to occur in infants exposed to lithium during the first trimester of gestation than in unexposed infants.
The increased risk could account for one additional cardiac malformation per 100 live births, Elisabetta Patorno, MD, and her colleagues wrote in the June 8 issue of the New England Journal of Medicine (2017;376:2245-54).
Dr. Patorno’s study is the largest conducted since then. It comprised more than 1.3 million pregnancies included in the U.S. Medicaid Analytic eXtract database during 2000-2010. Of these, 663 had first trimester lithium exposure. These were compared with 1,945 pregnancies with first trimester exposure to lamotrigine, another mood stabilizer, and to the remaining 1.3 million pregnancies unexposed to either drug.
There were 16 cardiac malformations in the lithium group (2.41%); 27 in the lamotrigine group (1.39%); and 15,251 in the unexposed group (1.15%). Lithium conferred a 65% increased risk of cardiac defect, compared with unexposed pregnancies. It more than doubled the risk when compared with lamotrigine-exposed pregnancies (risk ratio, 2.25).
The risk was dose dependent, however, with an 11% increase associated with 600 mg/day or less and a 60% increase associated with 601-900 mg/day. Infants exposed to more than 900 mg per day in the first trimester, however, were more than 300% more likely to have a cardiac malformation (RR, 3.22).
The investigators also examined the association of lithium with cardiac defects consistent with Ebstein’s anomaly. Lithium more than doubled the risk, compared with unexposed infants (RR, 2.66). This risk was also dose dependent; all of the right ventricular outflow defects occurred in infants exposed to more than 600 mg/day.
Dr. Patorno reported grant support from National Institute of Mental Health during the study and grant support from Boehringer Ingelheim and GlaxoSmithKline outside of the study. Other authors reported receiving grants or personal fees from various pharmaceutical companies.
msullivan@frontlinemedcom.com
On Twitter @Alz_gal
Cardiac malformations are three times more likely to occur in infants exposed to lithium during the first trimester of gestation than in unexposed infants.
The increased risk could account for one additional cardiac malformation per 100 live births, Elisabetta Patorno, MD, and her colleagues wrote in the June 8 issue of the New England Journal of Medicine (2017;376:2245-54).
Dr. Patorno’s study is the largest conducted since then. It comprised more than 1.3 million pregnancies included in the U.S. Medicaid Analytic eXtract database during 2000-2010. Of these, 663 had first trimester lithium exposure. These were compared with 1,945 pregnancies with first trimester exposure to lamotrigine, another mood stabilizer, and to the remaining 1.3 million pregnancies unexposed to either drug.
There were 16 cardiac malformations in the lithium group (2.41%); 27 in the lamotrigine group (1.39%); and 15,251 in the unexposed group (1.15%). Lithium conferred a 65% increased risk of cardiac defect, compared with unexposed pregnancies. It more than doubled the risk when compared with lamotrigine-exposed pregnancies (risk ratio, 2.25).
The risk was dose dependent, however, with an 11% increase associated with 600 mg/day or less and a 60% increase associated with 601-900 mg/day. Infants exposed to more than 900 mg per day in the first trimester, however, were more than 300% more likely to have a cardiac malformation (RR, 3.22).
The investigators also examined the association of lithium with cardiac defects consistent with Ebstein’s anomaly. Lithium more than doubled the risk, compared with unexposed infants (RR, 2.66). This risk was also dose dependent; all of the right ventricular outflow defects occurred in infants exposed to more than 600 mg/day.
Dr. Patorno reported grant support from National Institute of Mental Health during the study and grant support from Boehringer Ingelheim and GlaxoSmithKline outside of the study. Other authors reported receiving grants or personal fees from various pharmaceutical companies.
msullivan@frontlinemedcom.com
On Twitter @Alz_gal
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Key clinical point:
Major finding: The dose-dependent increased risks ranged from 11% to more than 300%, compared with unexposed pregnancies.
Data source: The Medicaid database review comprised more than 1.3 million pregnancies.
Disclosures: Dr. Patorno reported grant support from National Institute of Mental Health during the study and grant support from Boehringer Ingelheim and GlaxoSmithKline outside of the study. Other authors reported receiving grants or personal fees from various pharmaceutical companies.
Netherton Syndrome in Association With Vitamin D Deficiency
To the Editor:
Netherton syndrome (NS) is a rare genodermatosis that presents with erythroderma accompanied with failure to thrive in the neonatal period. Ichthyosis linearis circumflexa, or double-edged scale, is a typical skin finding. Chronic severe atopic dermatitis with diffuse generalized xerosis usually develops and often is associated with elevated IgE levels; however, a feature most associated with and crucial for the diagnosis of NS is trichorrhexis invaginata, or bamboo hair, that causes patchy hair thinning. The triad of ichthyosis linearis circumflexa, atopic dermatitis, and trichorrhexis invaginata is diagnostic of NS. Several other clinical features, including delayed growth, skeletal age delay, and short stature also can develop during its clinical course.1
Netherton syndrome is an autosomal-recessive disorder resulting from a mutation in the SPINK5 gene, which encodes a serine protease inhibitor important in skin barrier formation and immunity.2 Thus, frequent infections are common in these patients. Current treatment options include emollients and topical anti-inflammatory agents to minimize and control the classic manifestations of NS.
A 10-year-old girl with a history of allergic rhinitis and multiple food allergies presented to the dermatology clinic with a long history of diffuse generalized xerosis and erythema with areas of lichenification and scaly patches on the face, trunk, and extremities. She was born prematurely at 34 weeks and developed scaling and erythema involving most of the body shortly after birth. She exhibited severe failure to thrive that necessitated placement of a gastrostomy feeding tube at 8 months of age, resulting in satisfactory weight gain and the tube was later removed. A liver biopsy obtained at that time revealed early intrahepatic duct obstruction and early cirrhosis. She continued to have severe atopic dermatitis, poor growth, milk intolerance, and frequent infections. She had a history of dysfunctional voiding, necessitating the use of oxybutynin. The patient also was taking desmopressin to help with insensible water losses. She had no family history of dermatologic disorders.
At presentation she had diffuse scaling and erythema around the nasal vestibule and bilateral oral commissures. She also was noted to have coarse, brittle, and sparse scalp hair and eyebrows. Her current medications included hydrocortisone cream 2.5%, loratadine 10 mg daily, desmopressin 0.1 mg twice daily, and oxybutynin. Laboratory DNA analysis revealed 2 deletion mutations involving the SPINK5 gene that combined with physical findings led to the diagnosis of NS. Due to her severe growth retardation (approximately 6 SDs below the mean), she was referred to the pediatric endocrinology department. Our patient’s skeletal age was markedly delayed (6.5 years), and she was vitamin D deficient with a total vitamin D level of 16 ng/mL (reference range, 30–80 ng/mL). She is now under the care of a dietitian and taking a vitamin D supplement of 2000 IU of vitamin D3 daily. Growth hormone therapy trials have not been helpful.
An important feature of NS is growth retardation, which is multifactorial, resulting from increased caloric requirements, percutaneous fluid loss, and food allergies. Komatsu et al3 proposed that the SPINK5 inhibitory domain in addition to its role in skin barrier function is involved in regulating proteolytic processing of growth hormone in the pituitary gland. Its dysfunction may lead to a decrease in human growth hormone levels, resulting in short stature.3 This association suggested that our patient would be a good candidate for growth hormone therapy.
Furthermore, our patient was found to be vitamin D deficient, which was not surprising, as cholecalciferol (vitamin D3) is synthesized in the epidermis with UV exposure. This finding suggests that vitamin D deficiency should be suspected in patients with an impaired skin barrier. In addition to calcium regulation and bone mineralization, vitamin D plays a preventative role in cardiovascular disease, autoimmune diseases such as Crohn disease and multiple sclerosis, type 2 diabetes mellitus, infectious diseases such as tuberculosis and influenza, and many cancers.4
Vitamin D has 2 primary derivatives: (1) vitamin D3 from the skin and dietary animal sources, and (2) ergocalciferol (vitamin D2), which is obtained primarily from dietary plant sources and fortified foods. The most common test for vitamin D sufficiency is an assay for serum 25-hydroxyvitamin D (25[OH]D) concentration; 25(OH)D is derived primarily from vitamin D3, which is 3 times more potent than vitamin D2 in the production of 25(OH)D.5 The American Academy of Pediatrics recommends vitamin D replacement therapy for children with 25(OH)D levels less than 20 ng/mL (50 nmol/L) or in children who are clinically symptomatic.6 The Endocrine Society Clinical Practice Guidelines suggest screening for vitamin D deficiency only in individuals at risk.7 We suggest that serum vitamin D testing should be routine in children with NS and other atopic dermatitis conditions in which UV absorption may be impaired.
- Sun J, Linden K. Netherton syndrome: a case report and review of the literature. Int J Dermatol. 2006;45:693-697.
- Bitoun E, Chavanas S, Irvine AD, et al. Netherton syndrome: disease expression and spectrum of SPINK5 mutations in 21 families. J Invest Dermatol. 2002;118:352-361.
- Komatsu N, Saijoh K, Otsuki N, et al. Proteolytic processing of human growth hormone by multiple tissue kallikreins and regulation by the serine protease inhibitor Kazal-Type5 (SPINK5) protein. Clin Chim Acta. 2007;377:228-236.
- Wacker M, Holick MF. Vitamin D—effects on skeletal and extraskeletal health and the need for supplementation. Nutrients. 2013;5:111-148.
- Armas LA, Hollis BW, Heaney RP. Vitamin D2 is much less effective than vitamin D3 in humans. J Clin Endocrinol Metab. 2004;89:5387-5391.
- Madhusmita M, Pacaud D, Collett-Solberg PF, et al. Vitamin D deficiency in children and its management: review of current knowledge and recommendations. Pediatrics. 2008;122:398-417.
- Holick MF, Binkley NC, Bisckoff-Ferrari HA, et al. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2011;96:1911-1930.
To the Editor:
Netherton syndrome (NS) is a rare genodermatosis that presents with erythroderma accompanied with failure to thrive in the neonatal period. Ichthyosis linearis circumflexa, or double-edged scale, is a typical skin finding. Chronic severe atopic dermatitis with diffuse generalized xerosis usually develops and often is associated with elevated IgE levels; however, a feature most associated with and crucial for the diagnosis of NS is trichorrhexis invaginata, or bamboo hair, that causes patchy hair thinning. The triad of ichthyosis linearis circumflexa, atopic dermatitis, and trichorrhexis invaginata is diagnostic of NS. Several other clinical features, including delayed growth, skeletal age delay, and short stature also can develop during its clinical course.1
Netherton syndrome is an autosomal-recessive disorder resulting from a mutation in the SPINK5 gene, which encodes a serine protease inhibitor important in skin barrier formation and immunity.2 Thus, frequent infections are common in these patients. Current treatment options include emollients and topical anti-inflammatory agents to minimize and control the classic manifestations of NS.
A 10-year-old girl with a history of allergic rhinitis and multiple food allergies presented to the dermatology clinic with a long history of diffuse generalized xerosis and erythema with areas of lichenification and scaly patches on the face, trunk, and extremities. She was born prematurely at 34 weeks and developed scaling and erythema involving most of the body shortly after birth. She exhibited severe failure to thrive that necessitated placement of a gastrostomy feeding tube at 8 months of age, resulting in satisfactory weight gain and the tube was later removed. A liver biopsy obtained at that time revealed early intrahepatic duct obstruction and early cirrhosis. She continued to have severe atopic dermatitis, poor growth, milk intolerance, and frequent infections. She had a history of dysfunctional voiding, necessitating the use of oxybutynin. The patient also was taking desmopressin to help with insensible water losses. She had no family history of dermatologic disorders.
At presentation she had diffuse scaling and erythema around the nasal vestibule and bilateral oral commissures. She also was noted to have coarse, brittle, and sparse scalp hair and eyebrows. Her current medications included hydrocortisone cream 2.5%, loratadine 10 mg daily, desmopressin 0.1 mg twice daily, and oxybutynin. Laboratory DNA analysis revealed 2 deletion mutations involving the SPINK5 gene that combined with physical findings led to the diagnosis of NS. Due to her severe growth retardation (approximately 6 SDs below the mean), she was referred to the pediatric endocrinology department. Our patient’s skeletal age was markedly delayed (6.5 years), and she was vitamin D deficient with a total vitamin D level of 16 ng/mL (reference range, 30–80 ng/mL). She is now under the care of a dietitian and taking a vitamin D supplement of 2000 IU of vitamin D3 daily. Growth hormone therapy trials have not been helpful.
An important feature of NS is growth retardation, which is multifactorial, resulting from increased caloric requirements, percutaneous fluid loss, and food allergies. Komatsu et al3 proposed that the SPINK5 inhibitory domain in addition to its role in skin barrier function is involved in regulating proteolytic processing of growth hormone in the pituitary gland. Its dysfunction may lead to a decrease in human growth hormone levels, resulting in short stature.3 This association suggested that our patient would be a good candidate for growth hormone therapy.
Furthermore, our patient was found to be vitamin D deficient, which was not surprising, as cholecalciferol (vitamin D3) is synthesized in the epidermis with UV exposure. This finding suggests that vitamin D deficiency should be suspected in patients with an impaired skin barrier. In addition to calcium regulation and bone mineralization, vitamin D plays a preventative role in cardiovascular disease, autoimmune diseases such as Crohn disease and multiple sclerosis, type 2 diabetes mellitus, infectious diseases such as tuberculosis and influenza, and many cancers.4
Vitamin D has 2 primary derivatives: (1) vitamin D3 from the skin and dietary animal sources, and (2) ergocalciferol (vitamin D2), which is obtained primarily from dietary plant sources and fortified foods. The most common test for vitamin D sufficiency is an assay for serum 25-hydroxyvitamin D (25[OH]D) concentration; 25(OH)D is derived primarily from vitamin D3, which is 3 times more potent than vitamin D2 in the production of 25(OH)D.5 The American Academy of Pediatrics recommends vitamin D replacement therapy for children with 25(OH)D levels less than 20 ng/mL (50 nmol/L) or in children who are clinically symptomatic.6 The Endocrine Society Clinical Practice Guidelines suggest screening for vitamin D deficiency only in individuals at risk.7 We suggest that serum vitamin D testing should be routine in children with NS and other atopic dermatitis conditions in which UV absorption may be impaired.
To the Editor:
Netherton syndrome (NS) is a rare genodermatosis that presents with erythroderma accompanied with failure to thrive in the neonatal period. Ichthyosis linearis circumflexa, or double-edged scale, is a typical skin finding. Chronic severe atopic dermatitis with diffuse generalized xerosis usually develops and often is associated with elevated IgE levels; however, a feature most associated with and crucial for the diagnosis of NS is trichorrhexis invaginata, or bamboo hair, that causes patchy hair thinning. The triad of ichthyosis linearis circumflexa, atopic dermatitis, and trichorrhexis invaginata is diagnostic of NS. Several other clinical features, including delayed growth, skeletal age delay, and short stature also can develop during its clinical course.1
Netherton syndrome is an autosomal-recessive disorder resulting from a mutation in the SPINK5 gene, which encodes a serine protease inhibitor important in skin barrier formation and immunity.2 Thus, frequent infections are common in these patients. Current treatment options include emollients and topical anti-inflammatory agents to minimize and control the classic manifestations of NS.
A 10-year-old girl with a history of allergic rhinitis and multiple food allergies presented to the dermatology clinic with a long history of diffuse generalized xerosis and erythema with areas of lichenification and scaly patches on the face, trunk, and extremities. She was born prematurely at 34 weeks and developed scaling and erythema involving most of the body shortly after birth. She exhibited severe failure to thrive that necessitated placement of a gastrostomy feeding tube at 8 months of age, resulting in satisfactory weight gain and the tube was later removed. A liver biopsy obtained at that time revealed early intrahepatic duct obstruction and early cirrhosis. She continued to have severe atopic dermatitis, poor growth, milk intolerance, and frequent infections. She had a history of dysfunctional voiding, necessitating the use of oxybutynin. The patient also was taking desmopressin to help with insensible water losses. She had no family history of dermatologic disorders.
At presentation she had diffuse scaling and erythema around the nasal vestibule and bilateral oral commissures. She also was noted to have coarse, brittle, and sparse scalp hair and eyebrows. Her current medications included hydrocortisone cream 2.5%, loratadine 10 mg daily, desmopressin 0.1 mg twice daily, and oxybutynin. Laboratory DNA analysis revealed 2 deletion mutations involving the SPINK5 gene that combined with physical findings led to the diagnosis of NS. Due to her severe growth retardation (approximately 6 SDs below the mean), she was referred to the pediatric endocrinology department. Our patient’s skeletal age was markedly delayed (6.5 years), and she was vitamin D deficient with a total vitamin D level of 16 ng/mL (reference range, 30–80 ng/mL). She is now under the care of a dietitian and taking a vitamin D supplement of 2000 IU of vitamin D3 daily. Growth hormone therapy trials have not been helpful.
An important feature of NS is growth retardation, which is multifactorial, resulting from increased caloric requirements, percutaneous fluid loss, and food allergies. Komatsu et al3 proposed that the SPINK5 inhibitory domain in addition to its role in skin barrier function is involved in regulating proteolytic processing of growth hormone in the pituitary gland. Its dysfunction may lead to a decrease in human growth hormone levels, resulting in short stature.3 This association suggested that our patient would be a good candidate for growth hormone therapy.
Furthermore, our patient was found to be vitamin D deficient, which was not surprising, as cholecalciferol (vitamin D3) is synthesized in the epidermis with UV exposure. This finding suggests that vitamin D deficiency should be suspected in patients with an impaired skin barrier. In addition to calcium regulation and bone mineralization, vitamin D plays a preventative role in cardiovascular disease, autoimmune diseases such as Crohn disease and multiple sclerosis, type 2 diabetes mellitus, infectious diseases such as tuberculosis and influenza, and many cancers.4
Vitamin D has 2 primary derivatives: (1) vitamin D3 from the skin and dietary animal sources, and (2) ergocalciferol (vitamin D2), which is obtained primarily from dietary plant sources and fortified foods. The most common test for vitamin D sufficiency is an assay for serum 25-hydroxyvitamin D (25[OH]D) concentration; 25(OH)D is derived primarily from vitamin D3, which is 3 times more potent than vitamin D2 in the production of 25(OH)D.5 The American Academy of Pediatrics recommends vitamin D replacement therapy for children with 25(OH)D levels less than 20 ng/mL (50 nmol/L) or in children who are clinically symptomatic.6 The Endocrine Society Clinical Practice Guidelines suggest screening for vitamin D deficiency only in individuals at risk.7 We suggest that serum vitamin D testing should be routine in children with NS and other atopic dermatitis conditions in which UV absorption may be impaired.
- Sun J, Linden K. Netherton syndrome: a case report and review of the literature. Int J Dermatol. 2006;45:693-697.
- Bitoun E, Chavanas S, Irvine AD, et al. Netherton syndrome: disease expression and spectrum of SPINK5 mutations in 21 families. J Invest Dermatol. 2002;118:352-361.
- Komatsu N, Saijoh K, Otsuki N, et al. Proteolytic processing of human growth hormone by multiple tissue kallikreins and regulation by the serine protease inhibitor Kazal-Type5 (SPINK5) protein. Clin Chim Acta. 2007;377:228-236.
- Wacker M, Holick MF. Vitamin D—effects on skeletal and extraskeletal health and the need for supplementation. Nutrients. 2013;5:111-148.
- Armas LA, Hollis BW, Heaney RP. Vitamin D2 is much less effective than vitamin D3 in humans. J Clin Endocrinol Metab. 2004;89:5387-5391.
- Madhusmita M, Pacaud D, Collett-Solberg PF, et al. Vitamin D deficiency in children and its management: review of current knowledge and recommendations. Pediatrics. 2008;122:398-417.
- Holick MF, Binkley NC, Bisckoff-Ferrari HA, et al. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2011;96:1911-1930.
- Sun J, Linden K. Netherton syndrome: a case report and review of the literature. Int J Dermatol. 2006;45:693-697.
- Bitoun E, Chavanas S, Irvine AD, et al. Netherton syndrome: disease expression and spectrum of SPINK5 mutations in 21 families. J Invest Dermatol. 2002;118:352-361.
- Komatsu N, Saijoh K, Otsuki N, et al. Proteolytic processing of human growth hormone by multiple tissue kallikreins and regulation by the serine protease inhibitor Kazal-Type5 (SPINK5) protein. Clin Chim Acta. 2007;377:228-236.
- Wacker M, Holick MF. Vitamin D—effects on skeletal and extraskeletal health and the need for supplementation. Nutrients. 2013;5:111-148.
- Armas LA, Hollis BW, Heaney RP. Vitamin D2 is much less effective than vitamin D3 in humans. J Clin Endocrinol Metab. 2004;89:5387-5391.
- Madhusmita M, Pacaud D, Collett-Solberg PF, et al. Vitamin D deficiency in children and its management: review of current knowledge and recommendations. Pediatrics. 2008;122:398-417.
- Holick MF, Binkley NC, Bisckoff-Ferrari HA, et al. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2011;96:1911-1930.
Practice Points
- Netherton syndrome (NS) is characterized by severe atopic dermatitis, ichthyosis linearis circumflexa, and trichorrhexis invaginata.
- Children with NS are at increased risk for vitamin D deficiency.
- Consider screening patients with chronic severe dermatitis for vitamin D deficiency.
Late-to-bed adolescents may be early-to-diabetes
BOSTON – Late chronotype may have a deleterious impact on glucose homeostasis independent of obesity in preadolescents aged 10-13 years, according to a small study.
Late chronotype – or an individual’s preference for later sleep and food intake – is associated with higher body mass index (BMI), risk incidence of type 2 diabetes mellitus, hemoglobin A1c, and risk of hypertension in adults. It is also associated with higher BMI, lower dietary restraint, and lower HDL cholesterol in adolescents. This study was the first to focus on chronotype and glycemic control in children on the cusp of or in early puberty.
In participants tested during the summer months, the actigraphy-derived mid-sleep time on free days – an objective measure of chronotype – was associated positively with fasting plasma glucose (P = 0.048). “This is an important point because it highlights the objective measure of chronotype, whereas questionnaires can be more subjective,” said Magdalena Dumin, MD, at the annual meeting of Associated Professional Sleep Societies.
The researcher also noted that higher sleep fragmentation and lower sleep efficiency were both associated with hyperglycemia and hyperinsulinemia, independent of obesity.
“Our preliminary findings suggest that having a late chronotype and less efficient and more fragmented sleep in pre- and early adolescence may have a deleterious glycemic impact independent of obesity and pubertal stage,” she said.
“Advancing bedtimes may reduce glucose levels in preadolescents and adolescents,” Dr. Dumin surmised.
This study included 24 adolescents, 13 of whom were normal weight and 11 of whom were obese. They all underwent anthropometric measurements with fasting glucose, insulin, C-peptide, HbA1c, and lipid levels. Exclusion criteria included a clinical diagnosis of sleep, behavioral, or dietary problems. The obese subjects also underwent a 180-minute glucose tolerance test.
Chronotype was assessed via actigraphy over 1 week to provide mid-sleep time on free days, and secondarily through administration to chronotype questionnaires – the Children’s ChronoType Questionnaire and the Morningness-Eveningness Scale for Children.
Among the normal-weight participants, 31% were morning and 23% evening chronotype (the rest being neutral chronotype), and, in the obese subjects, 27% were morning and 36% were evening chronotype.
The obese subjects were more likely to be in puberty, and had higher systolic blood pressures, higher fasting plasma insulin and levels of insulin resistance, as measured by Homeostatic Model Assessment of Insulin Resistance. Hemoglobin A1c tended to be higher in the obese subjects (P = .06), but fasting plasma glucose did not differ significantly between the obese and normal-weight participants (P = .68).
“We chose this population due to the shift from morningness to eveningness that occurs during adolescence followed by a progressive return to an intermediate or early chronotype at the end of adolescence,” Dr. Dumin said.
Bedtime, wake time, and total sleep time were nearly identical between the two groups (7.84 hours and 7.62 hours; P = .49), although sleep efficiency was numerically lower in the obese subjects (87.0 vs. 89.8; P = .14), while sleep fragmentation was somewhat greater (20.16 vs. 17.38; P = .18).
Dr. Dumin suggested that a continuation of her research with more patients would be useful.
This study is supported by the Endocrine Fellows Foundation and the University of Chicago Institute of Translational Medicine. Dr. Dumin reported having no financial disclosures.
BOSTON – Late chronotype may have a deleterious impact on glucose homeostasis independent of obesity in preadolescents aged 10-13 years, according to a small study.
Late chronotype – or an individual’s preference for later sleep and food intake – is associated with higher body mass index (BMI), risk incidence of type 2 diabetes mellitus, hemoglobin A1c, and risk of hypertension in adults. It is also associated with higher BMI, lower dietary restraint, and lower HDL cholesterol in adolescents. This study was the first to focus on chronotype and glycemic control in children on the cusp of or in early puberty.
In participants tested during the summer months, the actigraphy-derived mid-sleep time on free days – an objective measure of chronotype – was associated positively with fasting plasma glucose (P = 0.048). “This is an important point because it highlights the objective measure of chronotype, whereas questionnaires can be more subjective,” said Magdalena Dumin, MD, at the annual meeting of Associated Professional Sleep Societies.
The researcher also noted that higher sleep fragmentation and lower sleep efficiency were both associated with hyperglycemia and hyperinsulinemia, independent of obesity.
“Our preliminary findings suggest that having a late chronotype and less efficient and more fragmented sleep in pre- and early adolescence may have a deleterious glycemic impact independent of obesity and pubertal stage,” she said.
“Advancing bedtimes may reduce glucose levels in preadolescents and adolescents,” Dr. Dumin surmised.
This study included 24 adolescents, 13 of whom were normal weight and 11 of whom were obese. They all underwent anthropometric measurements with fasting glucose, insulin, C-peptide, HbA1c, and lipid levels. Exclusion criteria included a clinical diagnosis of sleep, behavioral, or dietary problems. The obese subjects also underwent a 180-minute glucose tolerance test.
Chronotype was assessed via actigraphy over 1 week to provide mid-sleep time on free days, and secondarily through administration to chronotype questionnaires – the Children’s ChronoType Questionnaire and the Morningness-Eveningness Scale for Children.
Among the normal-weight participants, 31% were morning and 23% evening chronotype (the rest being neutral chronotype), and, in the obese subjects, 27% were morning and 36% were evening chronotype.
The obese subjects were more likely to be in puberty, and had higher systolic blood pressures, higher fasting plasma insulin and levels of insulin resistance, as measured by Homeostatic Model Assessment of Insulin Resistance. Hemoglobin A1c tended to be higher in the obese subjects (P = .06), but fasting plasma glucose did not differ significantly between the obese and normal-weight participants (P = .68).
“We chose this population due to the shift from morningness to eveningness that occurs during adolescence followed by a progressive return to an intermediate or early chronotype at the end of adolescence,” Dr. Dumin said.
Bedtime, wake time, and total sleep time were nearly identical between the two groups (7.84 hours and 7.62 hours; P = .49), although sleep efficiency was numerically lower in the obese subjects (87.0 vs. 89.8; P = .14), while sleep fragmentation was somewhat greater (20.16 vs. 17.38; P = .18).
Dr. Dumin suggested that a continuation of her research with more patients would be useful.
This study is supported by the Endocrine Fellows Foundation and the University of Chicago Institute of Translational Medicine. Dr. Dumin reported having no financial disclosures.
BOSTON – Late chronotype may have a deleterious impact on glucose homeostasis independent of obesity in preadolescents aged 10-13 years, according to a small study.
Late chronotype – or an individual’s preference for later sleep and food intake – is associated with higher body mass index (BMI), risk incidence of type 2 diabetes mellitus, hemoglobin A1c, and risk of hypertension in adults. It is also associated with higher BMI, lower dietary restraint, and lower HDL cholesterol in adolescents. This study was the first to focus on chronotype and glycemic control in children on the cusp of or in early puberty.
In participants tested during the summer months, the actigraphy-derived mid-sleep time on free days – an objective measure of chronotype – was associated positively with fasting plasma glucose (P = 0.048). “This is an important point because it highlights the objective measure of chronotype, whereas questionnaires can be more subjective,” said Magdalena Dumin, MD, at the annual meeting of Associated Professional Sleep Societies.
The researcher also noted that higher sleep fragmentation and lower sleep efficiency were both associated with hyperglycemia and hyperinsulinemia, independent of obesity.
“Our preliminary findings suggest that having a late chronotype and less efficient and more fragmented sleep in pre- and early adolescence may have a deleterious glycemic impact independent of obesity and pubertal stage,” she said.
“Advancing bedtimes may reduce glucose levels in preadolescents and adolescents,” Dr. Dumin surmised.
This study included 24 adolescents, 13 of whom were normal weight and 11 of whom were obese. They all underwent anthropometric measurements with fasting glucose, insulin, C-peptide, HbA1c, and lipid levels. Exclusion criteria included a clinical diagnosis of sleep, behavioral, or dietary problems. The obese subjects also underwent a 180-minute glucose tolerance test.
Chronotype was assessed via actigraphy over 1 week to provide mid-sleep time on free days, and secondarily through administration to chronotype questionnaires – the Children’s ChronoType Questionnaire and the Morningness-Eveningness Scale for Children.
Among the normal-weight participants, 31% were morning and 23% evening chronotype (the rest being neutral chronotype), and, in the obese subjects, 27% were morning and 36% were evening chronotype.
The obese subjects were more likely to be in puberty, and had higher systolic blood pressures, higher fasting plasma insulin and levels of insulin resistance, as measured by Homeostatic Model Assessment of Insulin Resistance. Hemoglobin A1c tended to be higher in the obese subjects (P = .06), but fasting plasma glucose did not differ significantly between the obese and normal-weight participants (P = .68).
“We chose this population due to the shift from morningness to eveningness that occurs during adolescence followed by a progressive return to an intermediate or early chronotype at the end of adolescence,” Dr. Dumin said.
Bedtime, wake time, and total sleep time were nearly identical between the two groups (7.84 hours and 7.62 hours; P = .49), although sleep efficiency was numerically lower in the obese subjects (87.0 vs. 89.8; P = .14), while sleep fragmentation was somewhat greater (20.16 vs. 17.38; P = .18).
Dr. Dumin suggested that a continuation of her research with more patients would be useful.
This study is supported by the Endocrine Fellows Foundation and the University of Chicago Institute of Translational Medicine. Dr. Dumin reported having no financial disclosures.
AT SLEEP 2017
Key clinical point: Preadolescents with a late chronotype show impaired glucose homeostasis independent of obesity.
Major finding: In participants tested during the summer months, the actigraphy-derived mid-sleep time on free days was positively associated with fasting plasma glucose (P = .048).
Data source: Observational study including 24 adolescents between 10 and 13 years of age. Thirteen were normal weight and 11 were obese.
Disclosures: Dr. Dumin reported having no financial disclosures. This study is supported by the Endocrine Fellows Foundation and the University of Chicago Institute of Translational Medicine.