Making a Difference for Children's Health
Jefferson’s Initiatives Aim to Help Kids Thrive
Jamie Green and her two young sons moved to the Philadelphia area from Wisconsin to be closer to her family. Their state medical assistance ended when they moved.
Green’s 9-year-old son, Maddox Green-Pethes, had difficulty seeing. The problem gave Maddy headaches and trouble with schoolwork. His vision needed attention, but the family was in health insurance limbo, waiting to qualify for Pennsylvania coverage.
Then Jamie Green heard about Give Kids Sight Day, an event held at Jefferson and Wills Eye Hospital, home of Jefferson’s Department of Ophthalmology. On that special day, about 1,200 uninsured or underserved children receive free vision screenings and, when needed, free eyeglasses. Volunteers helping at the event include Jefferson and Wills Eye physicians, Sidney Kimmel Medical College students and alumni, as well faculty and students from Jefferson’s health and science colleges.
Jefferson’s involvement is part of its institutional commitment to children’s health initiatives strengthening pediatric care, education and research throughout the region. That attention shows in a broad range of community services, from a special clinic for recently-arrived refugee children to SKMC students mentoring North Philadelphia children in science and medicine interests. In Jefferson’s laboratories, researchers are tackling serious pediatric health threats and finding new directions for treatments.
The focus on children’s health draws on Jefferson’s foundation of excellent pediatric care and medical education through the Department of Pediatrics at the Nemours/Alfred I. DuPont Hospital for Children in Delaware, where most SKMC students do their pediatrics rotations, as well as classes and clinics in Philadelphia.
Helping Children See
The numbers are stark: 22,000 Philadelphia children fail the state-mandated school vision screening every year. Of those, only about 5,000 are taken for follow-up with an eye doctor by their parents. That’s where Give Kids Sight Day comes in, providing services to children from Philadelphia and surrounding counties. Wills Eye also has an outreach vision program that has given eye care to more than 20,000 children in the School District of Philadelphia and area Boys & Girls Clubs.
Children arrive at Give Kids Sight Day with a variety of vision conditions, from no problems to significant concerns. “We see legally blind kids who only need a pair of glasses and they’ll be seeing 20/20. And we see kids who have serious eye-threatening disorders, like glaucoma, genetic eye disease, retinal detachment and cataracts, that require more sophisticated care,” says Alex V. Levin, MD ’82. Levin is chief of the Pediatric Ophthalmology and Ocular Genetics Service at Wills Eye.
In addition to Wills Eye and Jefferson, other sponsors of Give Kids Sight Day include Public Citizens for Children and Youth, Eagles Charitable Foundation, The School District of Philadelphia, Essilor Vision Foundation and First Hospital Foundation.
Jamie Green took both her sons to the 2015 event, making the trip to Jefferson from their home in Oxford, Chester County. Her 4-year-old, Aaron, was found to have astigmatism and was given glasses. Maddy’s eyesight problem was diagnosed as exotropia, a condition in which the eye turns outward. Left untreated, it can lead to vision loss. He was scheduled to see a pediatric ophthalmologist and surgeon, and the plan of care was explained.
“They had it organized so well,” Green says. “You felt when you left that you had concrete answers. I came home really grateful.”
Maddy had surgery on his affected eye in the summer of 2016. Now in 5th grade, he sees a Wills Eye pediatric ophthalmologist regularly, wears glasses and uses a patch for a few hours daily. His vision is improving. “So far, everything is looking really nice,” his mother says.
Care for Refugee Children
For some children, Jefferson provides the first opportunity they’ve had in a long time—sometimes in their entire lives—to receive full pediatric examinations and care. These children are refugees whose families are being resettled locally through several organizations.
The Nemours Pediatric Refugee Clinic at Jefferson began in 2010, when most of the children in its care were ethnic Nepali Bhutanese, born and raised in refugee camps. There also were some Burmese and Iraqi children, followed later by Congolese children. “Now we’re seeing a lot more Syrian refugees and a few others—eastern Europeans, West Africans and Afghanis,” says clinic director Christopher Raab, MD, who also heads the global health track for pediatrics residents at Nemours/Alfred I. DuPont Hospital for Children.
Located on Jefferson’s Philadelphia campus, the clinic provides a medical home for about 600 children. Some arrive with latent tuberculosis or parasitic infections, but most are “in pretty good shape,” Raab says. One family had four children with a rare condition, hypohidrotic ectodermal dysplasia, which affected their ability to sweat. The clinic worked with the family and school to help regulate the children’s body temperatures.
On one clinic day, third- and fourth-year SKMC students pepper Raab with questions about the patients they’re seeing, asking about everything from immunization catch-up schedules to bladder problems and diagnostic challenges. He talks with one student about the underweight child she just examined. Children may arrive from abroad significantly underweight, Raab says. As their nutrition improves, their weight and height increases quickly. “Which means they were stunted,” or short secondary to malnutrition, he explains.
Some families receive nutrition education from volunteers who are first- and second-year SKMC students. Because some refugee children are nutritionally healthy when they arrive here but become overweight after a year or so, the nutrition program aims to avoid that by offering information on healthy eating and answering families’ food questions. “They can’t find the fruits and vegetables they’re used to, in the form they’re used to,” says Naomi Newman, a second-year student. She notes that some families have to learn how to use a can opener. “It can mean the difference between a diet with vegetables in it and one without them.”
The student educators individualize sessions for cultural needs, giving advice that works with fasting during Ramadan or finding gelatin-free gummy vitamins to fit a Halal diet. Newman and Kaitlyn Petruccelli, a third-year SKMC student, presented a poster about the program’s efficacy at the 2016 meeting of the American Academy of Pediatrics.
Clinic health providers and families talk to each other with help from a phone-based interpretation service. Refugees may be unfamiliar with concepts such as refilling prescriptions or taking medicine on an “as-needed” basis. “It takes a long time to explain things in lay person’s terms with the use of an interpreter,” Raab says.
Families often aren’t comfortable talking about the stress and violence they’ve experienced. The clinic uses a screening tool for depression, anxiety and post-traumatic stress disorder. There’s a psychologist in the clinic as well as help from the Department of Psychiatry and other specialists.
Raab recalls one teenaged Iraqi girl who had been shot and had also witnessed the killing of her best friend. She received consistent care at the clinic and was referred through the Philadelphia Refugee Health Collaborative to a therapist specializing in immigrant and refugee mental health. “That’s a great example of a kid who could have been lost to follow-up, could have just been out there on her own. But because of the clinic and the collaborative, we were able to get her the proper care,” he says. She’s doing well now.
The clinic, Raab adds, fits with Jefferson’s commitment to serving the underserved. “It’s a great addition to the education of our students and residents, and a service to the kids we see.”
Mentoring Healthier Futures
At the Honickman Learning Center and Comcast Technology Labs in North Philadelphia, children from the community attend after-school and enrichment programs. For years, a group of Jefferson students known as Jeff Mentors has teamed with the Center to bring the children health- and science-related activities, field trips and guidance. “One of the special things about Jeff Mentors is that it’s a partnership within the community,” says group president, Qinglan Huang, a second-year SKMC student.
Jeff Mentors volunteers take middle-schoolers from the Center on an annual trip to the Franklin Institute. The children, says Huang, “are really excited to see us” and that exuberance fills the day.
Jeff Mentors recruits volunteers from all of Jefferson’s schools. Last year, the group held a health fair/career day for high schoolers at the Center, with workshops run by medicine, pharmacy and nursing students. “We want to encourage and instill an interest in science and the possibility of a career in health,” says Delfin Iglesia, a third-year SKMC student and Jeff Mentors past president.
During the event, the teenagers took part in hands-on activities, such as listening to heart sounds. They also watched medical care demonstrations, learned about body systems and even made diagnoses from clinical scenarios. Several Jefferson physicians participated. Faculty adviser for Jeff Mentors is R. Patrick McManus, assistant professor in the Department of Family & Community Medicine.
The student organizers would like to see Jeff Mentors stay connected with the children as they progress through school. In that way, SKMC mentors could offer advice about applying to college and, perhaps, planning for medical school.
While the mentors educate the children about health and help them envision professional careers for themselves, the children also enrich the Jefferson students’ education. “Learning about their backgrounds, how to better talk to them and address their personal concerns is something that we don’t get that much interaction with in medical school,” Huang says. Medical students learn about standardized patients, she explains—typically “the classic middle-aged, Caucasian demographic.” When they graduate, their patients are more diverse.
“Being able to understand the children’s concerns and knowing what we can do as physicians…that’s something we’re not going to be exposed to in a lecture,” says Huang. “This really brings the learning to life.”
Understanding the Impact of Lead Poisoning on Children’s Brains
The question posed by a colleague who was evaluating a lead-poisoned child in the late 1990s caught Jay S. Schneider, PhD, off-guard. After years of doing research on Parkinson’s disease, a neurological condition that usually affects older people, Schneider was asked if he knew about lead’s effect on children’s developing brains. “This was not an area I was familiar with. My initial response was that I wasn’t aware that lead poisoning was still an issue,” he recalls, referring to public attention given to the subject when lead-based paint was banned in 1976.
Schneider soon learned that children were still being exposed to lead, primarily through deteriorating lead-based paint in their homes, and suffering cognitive and behavioral deficits as a result. Yet, at that time, there were a limited number of basic research studies on lead’s developmental neurotoxicity and even fewer studies examining its effects on the brain at a molecular level. Most of the work only studied males. So Schneider expanded his research to look at molecular changes that occur when a fetal or infant brain is exposed to lead, how these changes might influence behavior, and if male and female brains respond similarly or differently to lead.
Since then, research conducted by Schneider, professor in the Department of Pathology, Anatomy and Cell Biology, and his Jefferson team has advanced understanding of the complicated effects of lead on young brains. That work, conducted in animals, continues as the researchers now look forward to starting a pilot study with children.
The shift comes at a time when, once more, the public is talking about lead poisoning. “Sadly, the debacle with lead-contaminated drinking water in Flint, Michigan has brought the issue of childhood lead poisoning to the forefront again,” Schneider says. Lead in drinking water has been a problem for decades and has been linked to elevated blood lead levels in children in numerous cities. “This is a problem that has not gone away. Childhood lead poisoning is still a major public health concern.”
Dr. Schneider’s research has shown that lead can have wide-ranging effects on the brain before and after birth, and that those effects are somewhat different in males and females. It found that rats exposed to lead during prenatal or early postnatal development have significant changes in gene expression. There are also significant changes in the epigenome, molecular modifications of DNA that switch genes on and off by chemical modifications to the DNA. These epigenetic changes are important, as they can incorrectly activate or silence genes. Effects were seen in the hippocampus and frontal cortex, brain regions where learning, memory, attention, and executive function processes are centered.
“We found that lead exposure even at low levels affects the expression of a variety of different genes in areas of the brain that are important for mediating various cognitive functions and behaviors,” Schneider says. “Lead can influence both the structural and functional integrity of the brain.”
His team has shown that lead’s effects differ by sex depending on the region of the brain. They also found that genetic background influences the biological response of an individual brain to lead, even when the amount of lead exposure is the same. This may explain why there is no single “behavioral signature” for childhood lead poisoning and how children living in the same house, with the same parents, and with similar lead exposures may have different neurobehavioral outcomes from that exposure.
Ongoing research is further investigating epigenetic changes caused by lead and examining the interaction between lead exposure and prenatal stress on the brain and behavior.
Dr. Schneider may also soon be working with lead-exposed schoolchildren in Trenton, New Jersey. Because lead poisoning produces cognitive deficits, the team proposes to explore using cognitive training exercises to see if those can help improve educational outcomes in lead-exposed children. The training is similar to that used to improve cognitive function in children with other types of acquired brain injuries.
“I view children who have been poisoned by lead as having a neurotoxicant-induced acquired brain injury. Why treat a child who has a brain injury from lead any different than a child with an acquired brain injury from some other source?” Schneider asks.
Finding Better Treatment for Newborns with Opioid Withdrawal
As opioid use has risen sharply in recent years, so has the number of infants with neonatal abstinence syndrome or NAS, a condition that begins shortly after birth and is caused by drug withdrawal. According to the Centers for Disease Control and Prevention, NAS incidence increased 300 percent from 1999 to 2013.
Symptoms include tremors, high-pitched crying, sleep problems and difficulties feeding. About half of NAS babies need pharmacological therapy, which in the US is typically morphine, says Walter Kraft, MD, professor in the Department of Pharmacology and Experimental Therapeutics and Director of the Clinical Research Unit. In recent years, Kraft and a team of Jefferson researchers have been studying the treatment of NAS with buprenorphine, a partial opioid agonist, as an alternative to morphine.
Nothing was known about buprenorphine’s effects on newborns when the researchers began their work. The drug acts like morphine in the brain but has a pharmacologic profile that has shown success in treating adult opioid withdrawal. The team thought it could be a better choice than morphine for infants and might shorten their length of treatment and hospitalization.
To conduct the research, the group collaborated with Jefferson’s Maternal Addiction Treatment Education and Research (MATER) program. MATER provides multidisciplinary and supportive services to women in addiction treatment and their children. The collaboration was key for the research. Women agreed to have their babies participate, Kraft believes, because they trust the staff and mission of MATER.
The researchers published a phase 1 study in 2011 that found buprenorphine was safe and effective. It was delivered under the tongue with a pacifier, a method that had never been described in newborns before. “We were not sure it was going to work,” Kraft says. Yet it did. Infants who received buprenorphine needed only 23 days of treatment compared to 38 days for those given morphine. Length of hospital stay also was lower: 32 days compared to 42 days.
Further work refined the research methods, leading to a phase 3, double-blind, double-dummy study [NCT01452789] which was recently completed and is now under peer review. While results are currently embargoed, “we are looking forward to sharing our results with the neonatology community” says Kraft.
Kraft is also exploring possible genetic influences in NAS. These could show why some newborns develop the condition and some do not. In parallel the group is is using blood levels of morphine or buprenorphine in NAS infants to develop a simulation model for predicting symptom control at different doses.
Discerning variability of response, Kraft says, is “the holy grail for clinical pharmacology. If the sources of variability in drug levels in the blood and response between babies, the better we can tailor therapies.”