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Neuroimaging essential for Zika cases

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About three years ago, Zika virus emerged as a newly recognized congenital infection, and a growing body of research indicates the damage it causes differs from other infections that occur in utero.

Seventy-one of 110 Brazilian infants at the highest risk for experiencing problems due to exposure to the Zika virus in the womb experienced a wide spectrum of brain abnormalities, including calcifications and malformations in cortical development, according to a study published July 31, 2019 in JAMA Network Open.

The infants were born at the height of Brazil’s Zika epidemic, a few months after the nation declared a national public health emergency. Already, many of the infants had been classified as having the severe form of congenital Zika syndrome, and many had microcephaly, fetal brain disruption sequence, arthrogryposis and abnormal neurologic exams at birth.

These 110 infants “represented a group of ZIKV-exposed infants who would be expected to have a high burden of neuroimaging abnormalities, which is a difference from other reported cohorts,” Sarah B. Mulkey, M.D., Ph.D., writes in an invited commentary published in JAMA Network Open that accompanies the Rio de Janeiro study. “Fortunately, many ZIKV-exposed infants do not have abnormal brain findings or a clinical phenotype associated with congenital Zika syndrome,” adds Dr. Mulkey, a fetalneonatal neurologist in the Division of Fetal and Transitional Medicine at Children’s National in Washington, D.C.

Indeed, a retrospective cohort of 82 women exposed to Zika during their pregnancies led by a research team at Children’s National found only three pregnancies were complicated by severe fetal brain abnormalities. Compared with the 65% abnormal computed tomography (CT) or magnetic resonance imaging (MRI) findings in the new Brazilian study, about 1 in 10 (10%) of babies born to women living in the continental U.S. with confirmed Zika infections during pregnancy had Zika-associated birth defects, according to the Centers for Disease Control and Prevention.

“There appears to be a spectrum of brain imaging abnormalities in ZIKV-exposed infants, including mild, nonspecific changes seen at cranial US [ultrasound], such as lenticulostriate vasculopathy and germinolytic cysts, to more significant brain abnormalities, such as subcortical calcifications, ventriculomegaly and, in its most severe form, thin cortical mantle and fetal brain disruption sequence,” Dr. Mulkey writes.

About three years ago, Zika virus emerged as a newly recognized congenital infection, and a growing body of research indicates the damage it causes differs from other infections that occur in utero. Unlike congenital cytomegalovirus infection, cerebral calcifications associated with Zika are typically subcortical, Dr. Mulkey indicates. What’s more, fetal brain disruption sequence seen in Zika-exposed infants is unusual for other infections that can cause microcephaly.

“Centered on the findings of Pool, et al, and others, early neuroimaging remains one of the most valuable investigations of the Zika-exposed infant,” Dr. Mulkey writes, including infants who are not diagnosed with congenital Zika syndrome.  She recommends:

  • Cranial ultrasound as the first-line imaging option for infants, if available, combined with neurologic and ophthalmologic exams, and brainstem auditory evoked potentials
  • Zika-exposed infants with normal cranial ultrasounds do not need additional imaging unless they experience a developmental disturbance
  • Zika-exposed infants with abnormal cranial ultrasounds should undergo further neuroimaging with low-dose cranial CT or brain MRI.
Breastfeeding Mom

Exclusive breastfeeding lowers odds of some schoolchildren having eczema

Breastfeeding Mom

Children exclusively breastfed for the first three months of life had significantly lower odds of having eczema at age 6 compared with peers who were not breastfed or were breastfed for less time, according to preliminary research presented during the American Academy of Allergy, Asthma & Immunology 2019 Annual Meeting.

Eczema is a chronic condition characterized by extremely itchy skin that, when scratched, becomes inflamed and covered with blisters that crack easily. While genes and the environment are implicated in this inflammatory disease, many questions remain unanswered, such as how best to prevent it. According to the Centers for Disease Control and Prevention (CDC), breastfed infants have reduced risks for developing many chronic conditions, including asthma and obesity.

“The evidence that being exclusively breastfed protects children from developing eczema later in life remains mixed,” says Katherine M. Balas, BS, BA, a clinical research assistant at Children’s National and the study’s lead author. “Our research team is trying to help fill that data gap.”

Balas and colleagues tapped data collected in Infant Feeding Practices Study II, a longitudinal study co-led by the CDC and the Food and Drug Administration (FDA) from 2005 to 2007, as well as the agencies’ 2012 follow-up examination of that study cohort. This study first tracked the diets of about 2,000 pregnant women from their third trimester and examined feeding practices through their babies’ first year of life. Their follow-up inquiry looked at the health, development and dietary patterns for 1,520 of these children at 6 years of age.

About 300 of the children had been diagnosed with eczema at some point in their lives, and 58.5 percent of the 6-year-olds had eczema at the time of the CDC/FDA Year Six Follow-Up. Children with higher socioeconomic status or a family history of food allergies had higher odds of being diagnosed with eczema.

“Children who were exclusively breastfed for three months or longer were significantly less likely (adjusted odds ratio: 0.477) to have continued eczema at age 6, compared with peers who were never breastfed or who were breastfed for less than three months,” Balas adds. “While exclusive breastfeeding may not prevent kids from getting eczema, it may protect them from experiencing extended flare-ups.”

American Academy of Allergy, Asthma & Immunology 2019 Annual Meeting presentation

  • “Exclusive breastfeeding in infancy and eczema diagnosis at 6 years of age.”

Sunday, Feb. 24, 2019, 9:45 a.m. (PST)

Katherine M. Balas BS, BA, lead author; Karen A. Robbins M.D., co-author; Marni Jacobs, Ph.D., co-author; Ashley Ramos Ph.D., co-author; Daniel V. DiGiacomo, M.D., co-author; and Linda Herbert, Ph.D., director of Children’s Division of Allergy and Immunology’s psychosocial clinical program and senior author.

Stricter state firearms laws can save children’s lives

In a new study presented at the Pediatric Academic Societies (PAS) 2018 annual meeting, Children’s researchers find that states with stricter firearm laws have lower rates of firearm-related deaths in children. The same cross-sectional analyses also found that states with laws that mandate universal background checks prior to firearm and ammunition purchases were associated with lower rates of firearm-related mortality in children, compared with states that lack these laws.

“Injuries due to firearms are the nation’s third-leading cause of pediatric death,” says Monika Goyal, M.D., M.S.C.E., director of research in the Division of Emergency Medicine and Trauma Services at Children’s National Health System and lead author of the research paper. “Firearm legislation at the state level varies significantly. Our findings underscore the need for further investigation of which types of state-level firearm legislation most strongly correlate with reduction in pediatric injuries and deaths.”

The research team analyzed data from the 2015 Web-based injury statistics query and reporting system maintained by the Centers for Disease Control and Prevention to measure the association between Brady Gun Law Scores – a scorecard that evaluates how strict firearms legislation and policies are in all 50 states – and state-based rates of firearm-related death among children aged 21 years and younger.

In 2015, 4,528 children died from firearm-related injuries. Eighty-seven percent were male; 44 percent were non-Latino black; their mean age was 18.

State-specific firearm-related mortality rates among children were as low as 0 per 100,000 to as high as 18 per 100,000. Median mortality rates were lower among the 12 states requiring universal background checks for firearm purchase at 3.8 per 100,000 children compared with 5.7 per 100,000 children in states that did not require background checks. Similarly, the five states with this requirement had a lower median mortality rate, 2.3 per 100,000 children, when compared with states that did not require background checks for ammunition purchase, 5.6 per 100,000 children.

“Newtown. Orlando. Las Vegas. Parkland. Those are among the mass shootings that have occurred across the nation in recent years. While these tragedies often are covered heavily by the news media, they represent a subset of overall pediatric injuries and deaths due to firearms. Pediatric firearm-related injuries are a critical public health issue across the U.S.,” Dr. Goyal adds.

“Pediatricians have helped to educate parents about other public health concerns, such as the danger posed by second-hand exposure to tobacco smoke or non-use of seat belts and car seats. In addition to presenting our most recent study results, members of our research group also hosted a workshop at PAS aimed at inspiring pediatric clinicians to similarly tackle this latest public health challenge and to advocate for firearm safety,” she says.

In addition to Dr. Goyal, study co-authors include Gia Badolato; Shilpa Patel, M.D.; Sabah Iqbal; Katie Donnelly, M.D.; and Kavita Parikh, M.D., M.S.H.S.

Roberta DeBiasi and Sarah Mulkey

Children’s National experts contribute to new Zika guidelines

Roberta DeBiasi and Sarah Mulkey

Roberta DeBiasi, M.D., M. S., and Sarah B. Mulkey, M.D., Ph.D., members of Children’s multidisciplinary Congenital Zika Virus Program, were among the experts invited to participate in a forum held in Atlanta at CDC headquarters in late August to formulate new Zika recommendations.

The Centers for Disease Control and Prevention (CDC) on Oct. 19, 2017 updated guidelines for evaluation of women, fetuses and infants exposed to the Zika virus during pregnancy. Although only women with symptoms will now be routinely tested, asymptomatic and symptomatic infants born to these women will still be tested for the Zika virus using blood and urine tests.

Infants who appear normal, whose mothers either had negative Zika results or who had not undergone testing, will not undergo Zika testing. These infants still will undergo a standard evaluation, including a detailed physical exam, hearing screen and routine developmental assessments. The revised Zika guidance includes input from practitioners on the front lines of the Zika epidemic, including Children’s National Health System clinicians.

“These changes in the recommendations for Zika testing should not be interpreted as Zika infection risks subsiding for pregnant women and their infants in the United States. It’s simply an acknowledgement of the limitations of current testing methods – which must occur within a narrow window after Zika exposure – and the poor predictive value of Zika testing right now,” says Roberta L. DeBiasi, M.D., M.S., chief of Children’s Division of Pediatric Infectious Diseases. Dr. DeBiasi and Sarah B. Mulkey, M.D., Ph.D., members of Children’s multidisciplinary Congenital Zika Virus Program, were among the experts invited to participate in the Zika forum held in Atlanta at CDC headquarters in late August to formulate the recommendations.

While all infants will receive a standard evaluation, expanded evaluations that include an ophthalmologic assessment, more detailed hearing evaluation and ultrasound of the newborn’s head will be reserved for infants born to mothers confirmed to be Zika positive or Zika probable, or for infants born with abnormalities potentially consistent with congenital Zika syndrome, regardless of maternal status.

The majority of U.S. infants who have been exposed to Zika in the womb appeared normal at birth, according to CDC registries. Now, the next wave of these normal-appearing babies will receive standard evaluations when they are born, including a newborn hearing screening. At each well-child visit, these infants will receive:

  • A comprehensive physical examination
  • An age-appropriate vision screening
  • Developmental monitoring and screening using validated tools

“This is a natural evolution in the diagnosis and screening strategy now that the peak of the first wave of Zika transmission appears to be over,” Dr. DeBiasi says. “While we continue to evaluate new possible cases of Zika infection among pregnant women in our practice, a sizable proportion of Children’s cases are Zika-exposed infants whose physical exam and neuroimaging appeared normal at birth. Through ongoing monitoring, we hope to learn more about these children’s long-term neurodevelopment outcomes.”

Study reveals asthma phenotypes in inner-city children

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What’s known

According to the Centers for Disease Control and Prevention, 8.6 percent of children across the nation, or 6.3 million kids, have asthma, a disease characterized by wheezing and coughing associated with airway obstruction, bronchial hyperresponsiveness, and inflammation of the airway. However, children with asthma with low socioeconomic status who live in inner cities experience a disproportionately high burden of illness. While treatment guidelines provide uniformity in managing allergy and allergic inflammation, such approaches may be misdirected when kids have asthma symptoms but lack allergy or allergic inflammation. Knowledge of distinct disease phenotypes can help to improve care.

What’s new

The Asthma Phenotypes in the Inner City study enrolled school-aged kids living in nine U.S. inner cities, including Washington, DC. The research team collected data about their asthma at the beginning of the one-year study and every two months as the kids’ asthma was managed according to accepted guidelines. Phenotypic analysis for 616 of these kids found their asthma clustered into five distinct groups. Cluster “A” was characterized by lower allergy, lower inflammation, and minimal symptoms. Fifteen percent of the kids fit within “A.” Another 15 percent of kids’ asthma fit within Cluster “B.” They had highly symptomatic asthma despite high step-level treatment and relatively low allergy and inflammation. Cluster “C” was distinguished by minimal symptoms, intermediate allergy and inflammation, and mildly impaired pulmonary physiology. Some 24 percent of kids fit within this group. The remaining kids fit within Cluster “D” or “E” and experienced progressively higher asthma and rhinitis symptoms as well as allergy and inflammation.

Questions for future research

Q: How does exposure to allergens, viruses, and irritants like tobacco smoke—taken individually as well as in combination—influence asthma severity and symptoms for these at-risk youths?
Q: What approaches to treatment might result from these studies?