summer 2019 | volume 33 | Issue 2

A journal of Dayton Children’s Hospital

acute flaccid : a case study in the pediatric intensive care unit by Kristin Mikolajewski, MSN, CPNP-AC/PC

1 learning objectives The patient’s admission exam was significant CSF Analysis: Following the completion of this article, for a left-sided facial Colorless and clear, the reader should be able to: droop, asymmetric Glucose 61 mg/dL, 1. Discuss diagnostic criteria for acute smile and inability to Protein 52 mg/dL, flaccid myelitis. completely close left WBC 18 cell/mm3 2. Review management and treatment eyelid. Pupillary reflexes (HIGH), RBC 28 options for acute flaccid myelitis. were normal. He was cell/mm3 (HIGH), 3. List complications associated with unable to shrug his Lymphocyte 76% acute flaccid myelitis. right shoulder or lift (HIGH), Eosinophil his right arm against 2%, Monocyte/ gravity. He had right Macrophage 22% upper extremity hy- CSF culture negative A previously healthy 13-year-old poreflexia and proximal (including fungal) unimmunized male presented to the weakness (shoulder emergency department with a one-day strength 2/5, elbow CSF strength 4/5, hand PCR negative history of right shoulder weakness and grip normal). All other CSF HSV PCR negative neck stiffness. Symptoms started extremities had normal approximately one week prior with strength and tone. CSF mycoplasma (103°F), sore throat, nasal congestion and He had no sensory pneumoniae IgM deficits. He was able and IgG positive dizziness. He was initially evaluated by his to ambulate and sit CSF Borrelia primary care physician, diagnosed with upright but required burgdorferi head support. He was sinusitis and prescribed a course of negative alert and oriented with amoxicillin. Two days later, he developed normal speech. CSF oligoclonal left-sided facial droop and difficulty bands negative Initial lab workup swallowing. He was taken to the local ED was notable for a CSF Aquaporin-4 where he was diagnosed with Bell’s palsy positive / antibody negative and prescribed a course of oral steroids. enterovirus PCR CSF arbovirus (polymerase chain The following day he developed right panel negative reaction) from shoulder weakness as well as neck stiffness. respiratory secretions, ANA negative He returned to the local ED where he a lumbar puncture Double stranded DNA showing cerebrospinal underwent MRI and CT scan of the head antibody negative fluid (CSF) pleocytosis and cervical spine which were both normal. (WBC 18/mm3) and a HSV PCR blood Due to the severity and rapid progression of positive mycoplasma negative symptoms, he was transported to the local pneumoniae CSF Stool viral culture antibody screen. children’s hospital for further evaluation. negative His CBC and BMP Additional history was noncontributory. were normal. Respiratory PCR No recent travel. No insect bites. No panel POSITIVE for vomiting. No diarrhea. No rash. No bowel Rhinovirus/enterovirus or bladder dysfunction. No known ill *repeat 48 hours later was negative exposures. Home medications included Blood culture negative ibuprofen for fever as well as the prednisone and amoxicillin as Urine culture negative previously prescribed. table 1. Laboratory data

2 with early identification from the blood. It is of respiratory failure. frequently used in the treatment of neurologic Despite 72 hours of disorders with aggressive steroid and autoimmune etiology.) antibiotic therapy, the patient’s condition The patient remained worsened with weak- hospitalized for 13 days. ness spreading to his He received a total of left upper extremity. five days of high dose He underwent repeat IV steroids, five plasma MRI which now showed exchange transfusions concern for cervical and 14 days of myelitis with a spinal doxycycline for the cord lesion extending treatment of from the level of the mycoplasma brainstem down to the pneumoniae. The level of C7 (figure 1). ceftriaxone and acyclovir were A team of physicians discontinued after 48 from , hours with negative infectious disease, CSF, blood and urine immunology, pediatric cultures. His respiratory critical care, neurosur- status remained stable, gery, pediatric surgery, requiring only a brief physical medicine and period of supplemental rehabilitation, and oxygen via nasal nephrology reviewed cannula. At time of the case. The team discharge, the patient concluded that this figure 1. MRI image demonstrating increased was able to support patient’s symptomatol- signal within the spine extending superiorly his own head, ogy and MRI findings into the brainstem starting at the level of the ambulate independent- were most consistent middle cerebellar peduncle and extending ly and tolerate a regular with acute flaccid downward into the medulla and cervical spinal diet by mouth. He had myelitis (AFM), an cord to the level of C7. minimal improvement acute neurologic in his extremity disorder characterized weakness or facial by unilateral Due to high risk for A nasogastric feeding palsy. On six-month flaccid weakness. respiratory failure, the tube was placed for follow-up, the patient While there are no patient was admitted nutrition due to cranial had completed evidenced-based to the pediatric nerve dysfunction and extensive rehabilitation treatment guidelines intensive care unit. aspiration risk. consisting of for AFM, there are case He was started on therapy, occupational two hours a day, five studies documenting empiric treatment therapy and speech days a week. He had improved outcomes for meningitis and therapy were consulted resolution of left upper with steroids and , for early rehabilitation extremity weakness. plasma exchange. which included treatment. NIFs His right shoulder At this point, the methylprednisolone (negative inspiratory weakness and left 30 mg/kg/day, force) and exhaled CO medical team decided 2 facial palsy were to proceed with ceftriaxone 100 mg/kg/ via nasal cannula were present but improved. plasma exchange. day and acyclovir 30 monitored to assist The probability of full (Plasma exchange, or mg/kg/day. recovery is unknown, , is a but he continues with procedure in which therapy in hopes inflammatory of continued mediators are filtered improvements.

3 defining acute transverse Guillain-Barre acute disseminated characteristics flaccid myelitis myelitis syndrome encephalomyelitis infarct

Encephalopathy not present not present not present present not present

Cranial nerve may or may not present may or may may or may not present dysfunction not be present not be present not be present

Muscle tone decreased, initially decreased, variable decreased often unilateral, decreased, ascending in UE > LE increased in nature, later stages, often often bilateral, symmetric, LE > UE LE > UE

Sensory typically not present present may or may present deficits present (clearly defined not be present sensory level)

Reflexes decreased acutely decreased variable decreased decreased, chronically increased

CSF Pleocytosis present present not present present not present

table 2. of acute flaccid myelitis LE = lower extremities UE = upper extremities

discussion high dose steroids and background hyporeflexia plasma exchange. Both or arefelxia and The definitive AFM is a rare, -like of these therapies have hypotonia. Cranial diagnosis for this case illness that is character- been associated with nerve dysfunction was challenging as the ized by acute onset of positive outcomes in occurs in 30 percent of patient’s symptom- flaccid weakness of one ATM and AFM. cases2. Sensory deficits atology did not meet or more extremities Additionally, while the are rare, but if present the classic criteria for a with specific MRI etiology of his illness are usually mild and single disease process. findings of lesions was never defined, transient. MRI findings This patient exhibited within the anterior the labs suggested an are most common in cranial nerve involve- horns of the gray infectious causality the cervical spine. The ment, which is less matter of the spinal related to enterovirus gray matter lesions likely with AFM. cord1. The illness or mycoplasma are initially diffuse However, the unilateral- typically occurs in pneumoniae. Both but become more ity of his weakness children (median age 6 of these pathogens localized to the anterior and the gray matter years) and affects more have documented horn cells over days to findings on MRI were males than females. associations with AFM weeks. CSF pleocytosis more characteristic of The onset is usually and ATM. The possi- is present in 80 AFM. One could argue rapid (within hours to bility of poliomyelitis percent of cases3. Many that this case meets days) and asymmetric. was discussed given his patients experience a the criteria for an The upper extremities unimmunized status, prodrome of respira- atypical presentation are more predominant- but was later ruled out tory or gastrointestinal of either acute trans- ly affected than the with negative stool viral symptoms, which verse myelitis (ATM) or lower, and the proxi- panel. The lack of data may include fever, AFM (table 2). In fact, mal muscle groups are surrounding the treat- approximately five some experts argue more predominantly ment of AFM made this days prior to onset of that AFM is a subset affected than the case challenging, and weakness2,4. Prognosis of ATM. Nonetheless, distal2. Patients exhibit highlights the need for is not well understood. this patient showed weakness consistent more robust research Aggressive rehabil- improvement with with a lower motor moving forward. itation therapy has neuron process with shown improvement in 4 clinical findings of functional outcomes epidemiology although complete The first U.S. outbreak recovery is rare. of AFM was reported Residual deficits range by the CDC in 2014 from mild to severe with 120 confirmed with the most cases in 34 states. severe cases resulting Since that time, there in tracheostomy for has been an upsurge long-term mechanical of biennial outbreaks ventilation as well as in the summer and fall gastrostomy tube for months. In 2016, there ongoing nutrition.2 To figure 2. This graph shows the number of AFM were 149 confirmed date, no fatalities have cases confirmed by the CDC as of March 29, 2019. cases in 39 states. In been directly related The case counts are subject to change as the CDC 2018, there were at to AFM.5 continues to investigate and confirm all of the least 228 confirmed cases reported. The most current data is available diagnosis cases in 41 states at: https://www.cdc.gov/acute-flaccid-myelitis/ (figure 2). So far in AFM is diagnosed afm-cases.html. 2019, there are four through physical exam- confirmed cases in four ination and MRI of the states. This data is as brain and spinal cord.1 not been identified, patients, including of March 29, 20191. The Lumbar puncture with epidemiologists have EV-70, EV-71, CDC is still working CSF analysis is also discovered that the coxsackievirus A to confirm cases from helpful. Diagnosis can biennial outbreaks of and B, echovirus, 2018 and 2019. be challenging as AFM AFM have coincided rhinovirus, West Nile has a similar presenta- The term AFM was with spikes in entero- virus, Japanese tion to transverse identified in 2014 in virus D-68 (EV-D68) encephalitis, St. myelitis and Guillain- response to the cases. Additionally, Louis encephalitis, Barre syndrome. The outbreaks. Prior to EV-D68 was the most cytomegalovirus and Centers for Disease 2014, similar illnesses commonly identified Epstein-Barr virus. All Control and Prevention were classified under pathogen in the of the stool specimens (CDC) defines AFM the umbrella term, respiratory specimens have tested negative as an illness with acute flaccid of AFM patients1. This for poliovirus1. acute onset of flaccid (AFP), suggests that EV-D68, Detection of pathogens extremity weakness which includes primarily a respiratory within the CSF is rare, with either 1) an MRI Guillain-Barre illness, is the primary as only four out of with spinal cord syndrome, transverse driver of the recent 551 confirmed cases lesion largely restrict- myelitis and upsurges. Some reported to the CDC ed to gray matter and poliomyelitis5. Not all experts have proposed have isolated CSF spanning one or more AFP cases demonstrate that the increase of pathogens1. vertebral segments the distinctive MRI EV-D68-associated pathophysiology (confirmed case), or findings as seen with AFM may be attribut- 2) CSF white blood AFM. Thus, a formal ed to the heightened The pathophysiology cell count > 5/mm3 case definition was neurotropism (affinity of AFM is not well (probable case). Spinal created by the CDC for nervous tissue) understood, but is cord lesions may not for tracking and with modern strains thought to be be present on initial reporting purposes. of EV-D68, which infectious or autoim- MRI, thus a negative Many patients that increases the mune in nature6. This MRI within the first presented prior to pathogen’s ability to leads to the theoretical 72 hours of onset of 2014 were classified as infect and kill neurons2. assumption that spinal limb weakness does transverse myelitis, but cord damage is either Aside from EV-D68, not rule out AFM1. would have likely met the result of a direct multiple pathogens the newly defined infection or a post- have been detected in AFM criteria. infectious or stool and respiratory autoimmune inflamma- While a definitive specimens of AFM tory response. This is etiology of AFM has 5 an important Experts theorize that exchange is likely to be poliomyelitis outbreaks discernment as the steroids may prevent harmful to the patient that left thousands of treatment for each further damage to (aside from known side children paralyzed. is different. Incorrect spinal cord tissue in effects and procedural To date, there is treatment may result an ongoing immune risks). no vaccine for in worsening of the or post-infectious preventative measures • Fluoxetine: disease process, inflammatory against AFM. Fluoxetine, a selective particularly in the response. On the serotonin reuptake summary setting of immune contrary, corticoste- inhibitor (SSRI), has suppressants and roids have been Community education shown in vitro activity active infection. associated with poorer and awareness of AFM against EV-D68 outcomes in EV-D68 is crucial as it impacts management but has not been and EV-71-associated the accurate and early associated with There are no neurological disease. identification of the improved outcomes evidence-based After a 2012 outbreak disease. Late in humans. A 2015- treatment guidelines in Cambodia, a recognition not 2016 multicenter study for AFM, but there are commission within only delays treatment concluded that AFM an increasing number the World Health but also inhibits patients treated with of case studies that Organization conclud- early specimen fluoxetine were more have documented the ed that testing where shedding likely to have severe potential benefits of were contraindicated of the pathogen may paralysis and poorer immune-targeted in the management be transient, such as outcomes in setting therapies such as of EV-71-associated with respiratory and of EV-D68. steroids, intravenous neurological disease. stool samples. The immunoglobulin (IVIG), The CDC further noted • Antivirals: There is delayed recognition and plasma exchange. that the incidence of no data to support of AFM has likely However, these EV-71-associated the use of antivirals contributed to the therapies remain neurologic disease in the treatment of underrecognition and controversial due to within the U.S. AFM unless there is underreporting of the theoretical concerns increased in 2018. suspicion of herpes disease process. The for immunosuppres- virus infection. medical community, • IVIG and plasma sion in the setting of along with the CDC, exchange: Multiple • Interferon: There is acute infection. In 2018, must continue to work case studies have no data to support the the CDC released a toward a better documented improved use of interferon in the Summary of Interim understanding of the outcomes with use of treatment of AFM. Considerations, which pathogenesis, IVIG and plasma ex- provides a discussion prevention prevention and change. However, IVIG, of potential treatment treatment strategies plasma exchange and Since AFM is suspected modalities for AFM7. for AFM. corticosteroids are to involve an infectious The key points are often used in combina- causality, prevention summarized below: tion, making it difficult strategies align • Corticosteroids: to discern the efficacy. with those of viral Corticosteroids While there is no sup- illnesses including have demonstrated portive data, there is effective hand hygiene improved outcomes also no data to suggest and avoiding close in the setting of white that IVIG or plasma contact with people matter, or upper motor who are ill. There is neuron, involvement increasing concern and spinal cord edema. surrounding the need for an EV-D68 vaccine as the AFM upsurges of 2014, 2016 and 2018 are similar to those of the

6 author CME questions Kristin Mikolajewski, MSN, CPNP-AC/PC 1. AFM is characterized by flaccid weakness Kristin Mikolajewski, MSN, CPNP-AC/PC, graduated of all extremities. from The Ohio State University with her master’s degree in nursing in 2009. She started her career a. True at Dayton Children’s in the pulmonary department b. False in 2010. She then practiced as a nurse practitioner in the cardiothoracic intensive care unit (CTICU) at 2. Plasma exchange and Nationwide Children’s for five years. She returned high dose steroids to Dayton Children’s where she currently practices have demonstrated in the pediatric intensive care unit. improved outcomes in patients with AFM. a. True references 5. Council of State and 8. Messacar K, Sillau S, b. False Territorial Epidemiol- Hopkins S, et al. Safety, 1. Centers for Disease ogists. Revision to the tolerability, and efficacy Control and Prevention. 3. Enterovirus D68 standardized surveil- of fluoxetine as an Acute flaccid myeli- outbreaks have lance and standardized anti-viral for acute tis: Case definition. coincided with recent case definition of acute flaccid myelitis. https://www.cdc.gov/ outbreaks of AFM. flaccid myelitis. https:// Neurology. 2018;92 acute-flaccid-myelitis/ a. True cdn.ymaws.com/www. (18):e2118-26. doi: hcp/case-definition. b. False cste.org/resource/ 10.1212/WNL.0000 html. Accessed March resmgr/2017ps/2017 000000006670 2019. psfinal/17-ID-01.pdf. 2. Messacar K, Accessed March 2019. Tyler, KL. Enterovi- 6. Washington State rus D68-associated Department of Health. acute flaccid myelitis. Acute flaccid myeli- JAMA. 2019;321(9):831- tis. https://www.doh. 832. doi: 10.1001/ wa.gov/Portals/1/ jama.2019.1016. Documents/5100/ 3. Maloney JA, Mirsky 420-068-Guideline DM, Messacar K, et al. -PolioAFM.pdf. MRI findings in children Accessed March 2019. with acute flaccid 7. Centers for Disease paralysis and cranial Control and Prevention. nerve dysfunction Acute flaccid myelitis: occurring during Interim considerations the 2014 enterovirus for clinical manage- D68 outbreak. AJNR ment of patients. Am J Neuroradiol. https://www.cdc.gov/ 2015;36:245-250. acute-flaccid-myelitis/ 4. Sejvar JJ, Lopez hcp/clinical-manage- AS, Cortese MM, et al. ment.html. Accessed Acute flaccid myelitis March 2019. in the United States, August-December 204: Results of nationwide surveillance. Clin Infect Dis. 2016;63:737-745.

7 female athlete triad

by Lora Scott, MD

In 2016, the AAP published its first policy statement on the female athlete triad. This article covers some of the highlights of that statement. Female athlete triad is an underdiagnosed condition that affects about half of female high school athletes. The triad consists of abnormalities in three areas: menstrual function, bone mineral density and energy availability. Each component occurs on a spectrum, ranging from mild to severe. Patients may present with one, two or all three components. It is rare for a female athlete to have all three components of the triad, representing around 1 percent of cases in high school female athletes. Up to 54 percent of high school female athletes have at least one component of the triad, with menstrual irregularities being the most common. If an athlete has any component of the triad, it should prompt screening for the other components.

learning objectives

Following the completion of this article, the reader should be able to: 1. Define the three components of the female athlete triad. 2. Learn available screening tools to use in clinic for the female athlete triad. 3. Learn basic treatment principles for the female athlete triad. 8 Types of menstrual irregularities

Primary amenorrhea

• No signs of puberty by age 14 OR

• No menarche by age 15 OR

• No menarche within 3 years of thelarche

Sports at highest risk NOT have a true eating triad is a diagnosis of Secondary for developing female disorder or intentional exclusion in this amenorrhea athlete triad include weight loss. More population, after • No menses for 3 endurance sports, often, they have ruling out other months sports with an aesthet- difficulty eating enough potential causes of ic component of their to sustain their level of menstrual irregularities Oligomenorrhea performance, and sports exercise. Athletes who (such as pregnancy). • Cycle longer than with weight classes. eat 2,000 kcal per day, Once other causes of 35 days Particularly high-risk but need 3,000 kcal amenorrhea are sports include cross per day to fuel their excluded, patients Luteal phase country, swimming, exercise, will still have with amenorrhea and deficiency cycling, cheer, physiological problems a history of low energy • Luteal phase shorter gymnastics, dance and due to their energy availability are than 11 days OR figure skating. Other risk deficit. Low energy diagnosed with factors include early availability can lead to functional hypothalamic • Low progesterone sports specialization, disruptions in menstru- amenorrhea. In this levels family dysfunction, al function and bone condition, the abuse and family mineralization. Athletes reproductive system table 1. Types of dieting. may initially present functions normally, menstrual irregularities with vague symptoms, but is suppressed by The condition is more such as fatigue. There lack of energy. The difficult to diagnose in is limited evidence that treatment is to improve Bone mineral density adolescent patients, athletes with menstru- energy availability until (BMD) is typically where irregular menses al irregularities have a normal menstrual measured using a DXA or amenorrhea can be measurable decrease in function resumes. scan at a pediatric normal, depending exercise performance. center, where results on the patient’s age. bone mineral density can be compared to However, it is important menstrual function Maximum formation age-based controls to make a diagnosis and Menstrual irregularities of bone mass occurs instead of adults. The manage this condition are extremely common during childhood and American College of when it occurs in in adolescent females, adolescence. Bone mass Sports Medicine has adolescents, since this with an incidence of typically peaks during proposed more rigorous is a time of peak bone 21 percent in the a person’s 20s, then criteria for interpreting growth. The condition sedentary female declines. Genetics, results in weight-bear- typically comes to adolescent population. activity level and diet ing athletes, since they attention from a In contrast, menstrual can all influence bone are expected to have screening questionnaire, irregularities occur at mass formation. increased bone-mass or when the patient has more than double the Inadequate bone compared to their a bone injury. rate in adolescent mass formation during sedentary peers.2 female athletes, adolescence will impact energy availability It is outside the scope occurring in up to a patient’s future risk of The vast majority of of this article to review 54 percent. developing osteoporosis adolescent females with how different types of as an adult. female athlete triad do Menstrual dysfunction sports can impact bone due to female athlete 9 health and density, normal, or could be 1. Do you worry about 5. Do you ever eat or to review other pathologic. Sometimes your weight or body in secret? medical conditions that it is necessary to composition? can affect bone health. question a patient’s 6. What age was Developing healthy mother about her early 2. Do you limit or your first menstrual bones during adolescent menstrual carefully control the period? adolescence is a history as well. foods that you eat? 7. Do you have multi-factorial process, Each screening tool 3. Do you try to lose monthly menstrual of which energy has its own scoring weight to meet cycles? availability plays a system, allowing a weight or image/ large—but not isolat- 8. How many physician to risk-strat- appearance ed—role. Menstrual menstrual cycles ify their athletes into requirements irregularities and/or have you had in low, moderate and high in your sport? stress injuries in the the last year? risk for having female bone often function as 4. Do you currently athlete triad. This 9. Have you ever had a a “check engine” light or have you ever score will help guide stress fracture? on the dashboard, in- suffered from an additional work-up dicating there could be eating disorder? and return-to-play a larger problem with decisions. This can bone health or energy table 2. Screening tool be reassessed as the availability. athlete is treated for diagnosis the condition. BMD/DXA testing for female athletes with

The American Please keep in mind or Academy of Pediatrics that this is only a brief Any of the following: Stress fracture PLUS (AAP) recommends screening tool, not • Current eating one of the following: using a questionnaire a diagnosis. A “yes” disorder • Low BMI (<18.5) to screen all adolescent answer to any question • Weight <85% ideal • More than 1 stress female athletes should prompt a more body weight fracture for the triad during thorough evaluation. • Weight loss of > • Menstrual a well check-up or Full evaluation includes 10% body weight dysfunction pre-participation an extensive nutrition- <6 months physical.1 Several al, menstrual, exercise, • Menstrual versions of screening and injury history. dysfunction for • History of prior tools are available, and Exam should include over 6 months eating disorder many centers will heart rate, orthostatic • Low energy • Chronic medical modify the tools to measurements, body availability for over conditions or fit their clinic popula- weight percentile for 6 months medication use tion. Table 2 outlines age and height, percent associated with the screening tool of ideal body weight, bone loss that is built into the and BMI. Other than • High risk stress fourth-edition pre- abnormalities in vital fracture location participation physical signs, those with the • Cyclists, swimmers evaluation consensus triad tend to have a monograph. Similar normal exam. Findings table 3. BMD testing indications questions appear on of lanugo, cold or dis- the Ohio pre-participa- colored extremities, or al laboratory and/or listed in table 3, and tion physical form for parotid gland enlarge- radiological testing. are consistent with the high school athletes. ment may signal that Labs typically focus AAP policy statement Unfortunately, these the athlete has a true on other causes of for female athlete triad.1 questions may not be eating disorder, such as irregular menses, such 1 treatment an adequate screening anorexia nervosa . as screening for preg- tool for younger Evaluation for female nancy, polycystic ovary The primary treatment adolescents, where athlete triad should syndrome (PCOS), and is to increase energy irregular menses or also include addition- thyroid disorders. BMD availability, either by amenorrhea could be testing indications are increasing caloric intake 10 and/or decreasing ex- that show they can references Prevalence of the female ercise levels. This leads improve BMD in the athlete triad in high 1. Weiss-Kelly AK, to subsequent increase adolescent population school athletes and Hecht S. American sedentary students. in BMD and restoration with female athlete Academy of Pediatrics Clinical Journal of of normal menstrual triad. Using OCPs to position statement: The Sports Medicine. function. The first steps regulate menstruation female athlete triad. 2009;19(5):421. in treatment include can make it more diffi- Pediatrics. 2016;138(2). increasing dietary in- cult to determine when 5. Scofield KL, 2. Nattiv A, Loucks AB, take by 200-600 kcal/ a patient truly meets Hecht S. Bone health et al. American College day, and decreasing her treatment goals. in endurance athletes: of Sports Medicine Runners, cyclists, and training volume by one position statement: The Calcium and vitamin D swimmers. Current day per week. Many female athlete triad. are independently Sports Medicine adolescent athletes Medicine & Science in inadequate in treating Reports. 2012;11(6): need a written Sports and Exercise. the triad, but do have 328-334. contract that is signed 2007;38(10). a positive effect on by the athlete, parent bone health. It is rec- 3. Vanheest JL, and medical team that ommended that they Rodgers CD, Mahoney outlines the treatment are given as part of a CE, De Souza MJ. plan and expectations CME questions larger treatment plan. Ovarian suppression for those involved. It impairs sport perfor- 4. Approximately can take one year or Bisphosphonates and mance in junior elite what percentage of longer for restoration other medications used female swimmers. high school female Medicine & Science in of normal menses after in treating postmeno- athletes have at least Sports and Exercise. reaching appropriate pausal osteoporosis one component of 2014;46(1):156-166. energy availability. are not helpful in the the female athlete adolescent female Treatment often 4. Hoch AZ, Pajewski triad? athlete triad. NM, Moraski L, et al. requires a team a. 5% approach, which should male athletes b. 20% include the treating There is emerging c. 50% physician, dietitian research that suggests and the team’s athletic d. 80% male athletes may trainer (if available) or e. 95% have a similar condi- author school nurse. In some tion, where low energy 5. A 16-year-old female cases, an exercise availability also impacts cross country runner physiologist and mental bone health and with a BMI of 22, health specialist may reproductive hormones. negative pregnancy be required as well. Without being able test, and amenorrhea Athletes should be to monitor menstrual every year during her encouraged to address cycles, it is difficult to sports season does issues about weight diagnose or study this NOT need further and nutrition with population as easily. evaluation. medical professionals, This is an area of a. True rather than coaching future research.1 staff or teammates. b. False summary 6. What is the best medications Lora Scott, MD treatment for Female athlete triad The use of oral con- irregular menses due is a surprisingly Lora Scott, MD, is traceptive pills (OCPs) to female athlete common condition that program director of is not recommended triad? can impact long-term sports medicine at unless it is needed for bone health when left Dayton Children’s. a. Increase calorie intake another reason, such as untreated. For more b. Decrease exercise preventing pregnancy. information, please Although the hormones c. Oral contraceptives read the AAP in OCPs can restore a d. A and B statement on the normal menstrual cycle, female athlete triad e. A, B, and C there are no studies 11 published in 2016. fetal cardiology now by Lubabatu Abdurrahman, MD, and Joseph Ross, MD

Congenital heart disease is a leading cause of infant morbidity and mortality. The overall incidence of congenital heart disease is estimated at six to 12 per 1,000 live births, and for moderate to severe congenital heart disease, six per 1,000 live births.1 Accurate and timely diagnosis of fetal heart disease can improve postnatal outcomes especially in those cases likely to require prostaglandin infusion to maintain patency of the ductus arteriosus after birth.2,3

Comprehensive fetal structure, function cardiology is a team and rhythm (figure 1). approach involving Ultrasound now primarily the pediatric/ permits precise and fetal cardiologist, detailed diagnosis maternal fetal medicine of structural and specialists and functional heart disease neonatologists. Variably (figure 2 and 3). and depending on the The goal is to better presence of associated understand the fetal defects, the fetus may patient taking into have additional account the difference practitioners involved: between the fetal and pediatric radiologist, postnatal circulation. geneticist and genetic Fetal echocardiography counselors, pediatric is broadly defined as a pulmonologist, detailed sonographic neurologist, urologist, evaluation used surgeons and learning objectives to identify and otolaryngologists. characterize fetal These specialties may heart anomalies Following the completion of this article, be involved in providing the reader should be able to: prior to delivery. It is a care both prenatally specialized diagnostic 1. Discuss what the field of fetal cardiology and postnatally. has to offer. procedure beyond 2. List the indications for referring a pregnant The cardiologist’s the “basic” and woman for fetal echocardiography. primary tool in “extended basic” fetal 3. Review the need for collaboration with assessing the fetus is cardiac screening maternal fetal medicine specialists and echocardiography. This performed as part of other specialists in caring for the fetus allows single/serial and routine obstetrical with congenital heart disease. accurate assessment(s) screening. of fetal cardiac 12 the fetal cardiac clinic at Dayton Children’s

The typical patient is referred by a maternal fetal medicine special- ist because of an abnormal/borderline fetal obstetrical ultrasound concerning for heart disease. Sometimes, the obstetrical ultrasound of the fetal heart is normal but mothers are referred for fetal echocardiography because of conditions predisposing the fetus to congenital heart disease. These conditions can include maternal heart disease, pregestational diabetes figure 1. Summary of fetal echo views: Four chamber, five chamber, mellitus, conception three vessel and tracheal view. by in vitro fertilization, and fetal aneuploidy.

Ultrasound scanning is performed by an ICAEL (Intersocietal Commission for the Accreditation of Echocardiography Laboratories) certified sonographer. The pediatric cardiologist reviews the images and consults with the family during the visit. The consultation includes a review of the findings of the study, implications for the health of the fetus/newborn and recommendations for delivery (mode and place). Further discussion addresses postnatal medical/ surgical interventions figure 2. Normal fetal echo: four chamber view that may be required.

13 • First-degree relative delivery and with of a fetus with immediate medical congenital heart and surgical postnatal disease critical care). These structural heart • Abnormal fetal heart defects may be rate or rhythm isolated or occur as • Known or suspected manifestations of fetal chromosomal a chromosomal abnormality: anomaly/syndrome Approximately such as Down 15 percent of infants syndrome and other with congenital trisomies, tuberous heart disease have sclerosis or DiGeorge recognizable chromo- syndrome (22q11.2 somal abnormalities4 deletion).

• Extracardiac anomaly 2. Secondary fetal heart (cleft lip and palate, disease: These fetal vertebral anomalies, cardiac disorders are tracheoesophageal often functional and figure 3. Axial (transverse) plane through the anomalies, renal occur secondary to fetal thorax: defines cardiac location, axis and abnormalities) some other fetal condition. Examples size relative to the fetal chest. Provides four • Hydrops chamber view of the fetal heart. include fetal • Increased nuchal cardiomyopathy translucency secondary to twin-to- When necessary, • Autoimmune twin transfusion • Monochorionic twins arrangements are diseases such as syndrome in (risk of twin-to-twin made to introduce the lupus erythematosus monochorionic twins, transfusion) family to the medical/ or Sjögren’s malposition and surgical staff that will syndrome only if classification of compression of the provide postnatal care anti-Ro/ fetal heart disease fetal heart in congenital to the baby. At times, SSA and anti-La/SSB diaphragmatic hernia, 1. Primary fetal serial studies are are present dilated cardiomyopa- heart disease: This is required for thy, and heart failure • Teratogen exposure typically structural. surveillance of secondary to severe (e.g., retinoic acid, Common abnormalities fetal health. fetal anemia. lithium, Vitamin K include defects indications for fetal antagonists, NSAIDS, as simple as small 3. Fetal arrhythmias: echocardiography some anti-hyperten- muscular ventricular Usually identified as an (maternal or fetal) sive medications and septal defects (which abnormal or irregular most anticonvulsant will often cause no fetal heart rate, these Maternal indications agents) health problems, arrhythmias account can include: usually close for approximately • Assisted reproductive • Maternal/Paternal spontaneously and 12 percent of all technologies such as history of congenital require no surgical referrals for fetal in vitro fertilization heart disease intervention), to a echocardiography. Fetal indications complex single An abnormal fetal • Familial inherited can include: ventricle anatomy heart rate is found in disorders (e.g., 22q11.2 often associated with one to three percent of deletion syndrome) • Abnormal cardiac heterotaxy syndromes all pregnancies. screening • Metabolic disorders (often life threatening examination such as diabetes and requiring careful mellitus, phenylke- management of tonuria and thyroid disease 14 o The most common o Atrioventricular (AV) fetal therapy of conclusion arrhythmias are conduction delay/ congenital heart • The diagnosis of premature atrial block: Most physi- disease cardiac disease in contractions, which, cians are familiar This is a rapidly the fetus is predom- in a heart with with the develop- evolving area of fetal inantly made with normal structure ment of fetal third cardiology. ultrasound. and function, are degree AV block generally benign. when the mother has prenatal • Newer technologies lupus erythematosus. such as magnetic o Supraventricular The most established More importantly, resonance imaging tachycardia (SVT) mode of fetal therapy the fetus often and magnetocardi- which occurs is administration of has normal AV ography (fetal ECG), typically at a rate of medication (typically conduction in are available and are 220-280 beats per anti-arrhythmic agents early pregnancy and advancing fetal care. minute (bpm). When or steroids) to the then can develop sustained, SVT mother for transplacen- • Medical and AV conduction can cause cardiac tal transfer to the fetus. interventional delay progressing dysfunction and More recently maternal treatments for certain (relatively) acutely failure. It is rarely hyperoxia therapy is fetal cardiac disease to complete heart associated with being explored coupled with block. Close structural heart for diagnostic and careful planning monitoring of the defects but can be therapeutic purposes for delivery room mechanical “PR” associated with in certain obstructive care often results interval by fetal Ebstein’s anomaly. fetal structural heart in improved fetal Doppler defects. Interventional outcomes. o Atrial flutter that interrogation using fetal cardiac therapies typically has a serial echocardio- • Fetal cardiology is range from minimally slightly higher grams is especially a highly specialized invasive fetoscop- ventricular rate of helpful in managing and rapidly ic-guided procedures 220-240 bpm. It can these fetuses. advancing field. (fetal transfusions, occur either as an It is important to note laser therapy for twin- • Ready access to isolated event that certain sustained to-twin transfusion, fetal cardiology or secondary to fetal arrhythmias aortic valvuloplasty) and maternal fetal cardiomegaly and can cause hydrops/ to open uterine fetal specialists should, hydrops. heart failure surgery. hopefully, allow o Premature (primary arrhythmias). prenatal diagnosis natal ventricular Vice versa, fetal and care of most contractions occur arrhythmias can occur Careful management complex cardiac much less frequently secondary to hydrops/ of place, mode and diseases in the future. than premature atrial heart failure (secondary time of the delivery of • Comprehensive fetal contractions and are arrhythmias). the fetus is a natural cardiology care is more likely to be continuum of the care provided here at associated with of the fetus with a Dayton Children’s in structural heart congenital heart defect. collaboration with defects. Fetal and obstetrical our regional maternal risks are taken into fetal medicine consideration when specialists. planning for delivery.

15 references authors CMEcaregivers questions are urged to keep these devices out 1. Ferencz C, Rubin JD, 7. A 25-year-old woman of reach. For patient/ McCarter RJ, Brenner with no family family information on JI, Neill CA, Perry LW, history of congenital button battery inges- Hepner SI, Downing heart disease and tions, see the American JW. Congenital heart with controlled Academy of Pediatrics disease: Prevalence pregestational healthychildren.org at livebirth: The diabetes should website at https://www. Baltimore-Washington have a fetal healthychildren.org/ Infant Study. Am J echocardiogram. English/safety-preven- Epidemiol. a. True tion/at-home/Pages/ 1985;121:31-36. Button-Battery-Injuries-b. False 2. Donofrio MT, duPles- Lubabatu Joseph E. Ross, MD, 8.in-Children-A-Growing- Isolated premature sis AJ, Limperoulos C. Abdurrahman, MD, FACC Risk.aspx.atrial contractions Impact of congenital FACC in a fetus with no Joseph E. Ross MD, heart disease on fetal structural heart Lubabatu FACC, is a board brain development. disease and normal Abdurrahman, MD, certified pediatric Current Opinion in FACC, is a board cardiologist and heart function are Pediatrics. 2011;23: certified pediatric the division chief of likely to be benign. 505-511. cardiologist and pediatric cardiology a. True is head of the at Dayton Children’s. 3. Holland BJ, Myers b. False fetal cardiac He completed JA, Wood CR Jr. clinic and special his residency in 9. Dichorionic/dizygotic Prenatal diagnosis of echocardiographic pediatrics and twin pregnancy is a critical congenital heart techniques at pediatric cardiology risk factor for twin- disease reduces risk of Dayton Children’s. fellowship at to-twin transfusion Her pediatric Rainbow Babies and death from cardiovas- syndrome and cardiology fellowship Children’s Hospital/ cular compromise should be followed prior to planned was at Boston Case Western Children’s Hospital/ Reserve University in with serial fetal cardiac surgery: Harvard Medical Cleveland, Ohio. echocardiogram. A meta analysis. School in Boston, a. True Ultrasound Obstet Massachusetts. She b. False Gynecol. 2015;45: did her residency 631-638. in pediatrics at Rainbow Babies and 4. Ferencz C, Neill CA, Children’s Hospital/ Boughman JA, Rubin Case Western JD, Brenner JI, Perry Reserve University in LW. Congenital Cleveland, Ohio. cardiovascular malformations associated with chromosome abnormalities: An epidemiologic study. J Pediatr. 1989;114-79.

5. Figures 1 and 2 6. Cluver, C. (2019). provided by Greggory Normal fetal echocar- R. DeVore, MD. diogram | Radiology Maternal-fetal Case | Radiopaedia.org. medicine. Pasadena, [online] Radiopaedia. California. org.

16 early diagnosis and treatment of cytomegalovirus-related hearing loss: Dayton Children’s protocol

by Robert Goldenberg, MD

What if a type of congenital nerve deafness Pittsburgh Medical Center and several could be treated with medical management years on the staff of Children’s Hospital as well as with hearing aids? Los Angeles. Hearing loss* in newborns caused by the cytomegalovirus (CMV) might Ankur Patel, DO, asked this question when be successfully treated with medication if he first joined the pediatric ENT department detected in the first few weeks of life. at Dayton Children’s in 2017. He knew the answer from his fellowship in pediatric *In this article, the term “hearing loss” will be used exclusively to mean sensorineural hearing loss and otolaryngology at the University of not any form of conductive loss caused by fluid or other middle ear pathology.

background occurs in immunocom- promised individuals.2 Human CMV belongs learning objectives to the family of herpes CMV affects between viruses (figure 1). The 20-40,000 infants per incidence of CMV in year and is the most Following the completion of this article, the the general population commonly transmit- reader should be able to: of the United States ted virus to a fetus3. It 1. Review the current opinions regarding increases with age is the most common the management of congenital CMV. leveling off at 80-90 congenital infection in 2. Describe the present techniques of percent by 80 years newborns. Intrauterine identifying newborn hearing loss. of age1. It is typically infections can occur 3. Discuss the methods of early identification asymptomatic but during any trimester and treatment of CMV-related deafness. viral latency remains of pregnancy. Transmis- throughout life and can sion to a fetus during be reactivated at any the first trimester, time, which most often

17 newborn is tested in the first three weeks of life. After three weeks the infant’s inoculation may be due to a primary acquired virus and therefore not qualify as congenital. This has also made it difficult to estimate the proportion of hearing loss in children that is attributed to congen- ital CMV. One study estimates that con- genital CMV infections account for 21 percent of all hearing loss at birth and 25 percent by figure 1. Photomicrograph of the cytomegalovirus 4 years of age. These in a sample of human saliva numbers suggest that CMV is the leading non-genetic cause of however, is associated In developed coun- atic infants, most will hearing loss in children with the greatest risk of tries, 50 percent of have a bilateral loss and born in the United severe fetal infection, women of childbear- asymptomatic infants States8. organ involvement, ing age have evidence will have a unilateral Congenital CMV occurs and subsequent of CMV infection (i.e., loss. In both groups the only if the mother is developmental CMV seropositive). The hearing loss is usually infected with the virus sequelae4. Over one- incidence of congenital severe to profound. during pregnancy. If half of symptomatic CMV infection parallels The hearing loss may the child is infected infants will have long- maternal CMV preva- be delayed for six to with the virus after term sequelae. Lower lence. Infection is most seven years and can be delivery, he or she is rates of neurodevelop- often asymptomatic unstable, fluctuating not at increased risk mental sequelae 85-90 percent of the or progressive. of developing any of are reported in asymp- time and is symptom- Hearing loss due to the sequelae (including tomatic infants with atic in 10-15 percent of CMV does not have a hearing loss) of a sensorineural hearing infants5. The symptoms pathognomonic audio- CMV infection. These loss being the most of fetal infections metric configuration sequelae are more common manifestation. can include mental re- and varies in the likely to develop in tardation, neurological Fetuses and neonates severity of the loss7. utero if the mother defects, cerebral palsy, with congenital CMV Complicating estima- had a primary , developmen- infection show that tion of its incidence is infection rather than a tal delays and loss of the virus can infect a the fact that less than reactivation of a previ- vision. About 12 variety of cell types half of the affected ous infection, and are percent of CMV resulting in inflammato- children are born with more likely to occur if infected infants will ry infiltrates and organ the loss and the other the infection is in the experience some disease with respect half do not develop it first half of the degree of hearing loss; to the inner ear. until the early elemen- pregnancy. Infants 30 percent of these Infected cells can tary school years. born to seroimmune infants will have include epithelial cells mothers are not other symptoms and Congenital CMV of the semi-circular completely protect- 10 percent will have infection can only be canals, vestibulae, ed from hearing loss, no other symptoms6. confirmed if the cochlea and other although it is often Among the symptom- structures.

18 milder than seen in birth. It is estimated • Sepsis or meningitis functional. An auditory infected infants follow- to occur in one to three stimulus (a tone or • Ventilator ing primary maternal out of every 1,000 click) creates a dependence infections9. About 30 newborns11. response from the co- percent of infected • Ototoxic drugs chlea that is measured Infants who are at risk pregnancies result in by a microphone; both for hearing loss should The field of pediatric infected fetuses. stimulus and response have frequency specif- audiology has grown are measured by a Prevention of exposure ic diagnostic auditory dramatically in the probe tip in the ear to CMV during preg- brainstem response past several decades, canal. The accuracy of nancy is obviously a (ABR) testing as soon and the ability to test the response can be challenge10. Universal as possible. Prior to hearing at increasing- affected by ambient screening of pregnant universal screening ly younger ages has noise, ear canal women has been programs, threshold helped generate this obstruction and middle discussed but not ABR testing was per- growth. Nowhere is ear pathology. routinely recommend- formed only on infants this more obvious than ed. Obviously a identified as having in the technological The AABR test seronegative pregnant high risk factors. These advances of objective assesses auditory woman should attempt risk factors are still hearing tests, which function from the to limit her exposure to used today. The risk do not require any cochlea through the the virus. Body fluids factors help identify in- response or active auditory brainstem. (saliva, urine) are fants requiring thresh- participation from the An auditory stimulus probably the most old ABR assessment child. In particular, the (usually a click set at common means of instead of a hearing science of electrophys- 35dBHL) delivered transmission, so aware- screening test. iology has enabled through small dispos- ness of this fact is quite Threshold ABR measurement of able insert earphones significant; frequent testing provides hearing in newborns generates a waveform. hand washing is there- hearing threshold data. with a high degree of The waveform is fore very important. Hearing screening accuracy and reliability. recorded on a com- The use of CMV is used to rule out puter through surface Hearing screening of hyperimmune globulin more than a mild electrodes placed on newborns can be infusion in pregnant hearing loss. the infant’s forehead, performed in the women has not been shoulder and nape of High risk factors newborn nursery or shown to reduce the the neck. The screening include: newborn intensive care incidence of congenital results are ear specific. unit within the first few CMV sequelae. • Family history of If these tests indicate days of life by trained Attempts to develop hearing loss a “refer” response technicians and does a vaccine for the (unilateral or bilateral), • History of congenital not require the partic- prevention of the infant will require infections (CMV, ipation of fully trained developing a CMV further evaluation. rubella, herpes audiologists. The tests infection have not simplex virus, are automated; they A licensed audiologist proven successful HIV, syphilis, use standardized re- performs this further as of now. toxoplasmosis) sponse parameters and evaluation (usual- identifying hearing templates to generate ly in an academic or • Low birth weight: loss in newborns a simple “pass/refer” children’s hospital <1.5 kg result. Infant hearing setting). Tympanom- Universal hearing • Low Apgar score: screening can be etry and repeat OAE screening programs for <5 at 1min, <7 at 5min performed by an OAE testing are often per- newborns have been (otoacoustic emissions) formed, but the most used in the United • Hypoxia or an AABR (automat- important part of the States for several • Seizures ed auditory brainstem follow-up evaluation decades. It was response) test. is the threshold ABR. mandated for the • Prenatal infections Threshold ABR testing State of Ohio in 2004. The OAE test can as- • Craniofacial is based upon the same Hearing loss is one sess the integrity of the anomalies electrophysiological of the most common cochlea and therefore principles as a screen- anomalies present at • Hyperbilirubinemia infer that the cochlea is 19 ing ABR. However, 2 ABR examples for the CMV project (normal and moderate loss) unlike a screening ABR, a threshold ABR can V V determine the presence or absence of hearing loss across the frequency spectrum; Threshold Click Stimulus ABR Threshold Click Stimulus this is done by varying response at 10dBHL consistent ABR response at 50dBHL the frequency and with normal mid and/or high consistent with normal mid intensity of the test frequency hearing. and/or high frequency hearing. stimuli (figures 2 and 3). If a hearing loss is figure 2. ABR demonstrating normal figure 3. ABR demonstrating severe present, the type and hearing in a newborn infant. hearing loss in a newborn infant. degree of loss can be determined. ABR testing provides an In the past, CMV has Since at times it can decade they have been objective, not a been identified in cell be difficult to obtain used for the treatment behavioral, estimate of culture from a urine a urine sample from a of congenital CMV an infant’s hearing level. specimen. Tissue newborn, PCR infections13. Antiviral culture isolation is slow performed on salivary therapy with either As with almost all and may take up to two samples has been parenteral ganciclovir hearing evaluations, to three weeks to have shown to be both or oral valganciclovir a battery of tests an answer. A shell viral sensitive and specific. does carry risks, provides an opinion assay is a modified tis- Saliva is now especially the that is validated by sue culture technique, considered to be the development of repeat testing over which reduces the specimen choice and neutropenia. time. The audiologist time considerably but the PCR technique However, with diligent can then recommend still may take a week to be the technique monitoring, antiviral further testing, or so. Viral antigen- of choice for CMV treatment is current- observation, treatment emia assay has been diagnosis. ly recommended for and follow-up. commonly used for symptomatic newborns medical management quantification in blood with central nervous identification of of CMV in the newborn congenital CMV specimens. Polymerase system (CNS) disease infection in chain reaction (PCR) is Antiviral agents or severe focal organ the newborn a widely available, rapid specifically for the disease. and sensitive method treatment of CMV Antiviral therapy has It is absolutely of CMV detection. PCR were initially been studied in new- essential for the amplifies viral nucleic developed during the borns with hearing loss. clinician to determine acids targeting CMV AIDS epidemic of the In a randomized and if an infant’s CMV DNA. Immunochemis- 1980s. Four antiviral controlled clinical trial, infection is acquired try can be performed drugs are licensed for hearing loss associated either congenitally on tissue or body fluid the treatment of CMV with CMV was treated or postnatally. The samples. Nucleic acid infections: ganciclovir, with intravenous ganci- accepted standard for sequence is based valganciclovir, foscar- clovir. Auditory brain- diagnosing congenital upon an amplification net and cidofovir. stem responses were CMV infection in new- technique (NASBA). These agents began used to monitor hear- borns is virus detection Hybrid capture assay as medications to treat ing during treatment, in the first three weeks uses RNA probes to existing infections which was determined of life. If a specimen detect and quantify but have additionally to be stabilized at for testing is obtained viral DNA. Serologic evolved into 6 months and one after this age, exposure assays are generally medications to year of life14. to the virus may have not necessary for the prevent infections occurred postpartum diagnosis of congenital primarily in transplant and this would not CMV infection.12 recipients. For almost a represent a congenital CMV infection.

20 A retrospective study 2. Referral sources Ravi Elluru, MD, PhD of infants with isolated will be strongly Chief, division of pediatric ENT hearing loss associated encouraged and with CMV who received Ankur Patel, DO educated for the Pediatric ENT 12 months of valganci- need to make this clovir were reported. Linda McGinnis, MA, CCC-A happen in a Of 80 ears assessed Audiology manager timely way. (38 infants with Sherman Alter, MD 3. At the appointment unilateral loss and Chief, division of infectious disease for the hearing 21 infants with Pam Morgan, BSN, RN evaluation a buccal bilateral loss), 55 ears Director, surgical services (pediatric ENT) swab to obtain a (69 percent) showed Robert Goldenberg, MD saliva specimen will improvement and Pediatric ENT be performed by the two ears (3 percent) 15 audiologist. worsened . table 1. CMV task force 4. The saliva specimen Twenty-three infants will be analyzed in with culture proven Dayton Children’s lab symptomatic CMV The task force worked force would like to by the PCR method infection were treated together during 2018- acknowledge and in order to generate a with ganciclovir intra- 2019 to create this recognize the help of report within one to venously for six weeks protocol. They studied so many members of two days.This report followed by valganci- some of the programs Dayton Children’s staff will result in one clovir orally for 12 already in existence who assisted with the of the four months. At age 1 year nationally to learn from establishment of this recommendations or greater, 76 percent their experience. Many protocol. of the components made in table 2. of these infants’ ears Dayton Children’s of this protocol were had normal hearing as protocol is as follows: 5. In addition to the compared to a baseline already operational at above, a hearing of 54 percent.16 Dayton Children’s and 1. Newborns who fail aid may or may not it was simply a matter their screening test be recommended Ongoing trials continue of putting the pieces and are referred to depending upon the to investigate valganci- together. However, this Dayton Children’s for amount of hearing clovir therapy in infants protocol is unique in a complete newborn loss present. with congenital CMV its structure and may hearing evaluation infections and isolated in turn stimulate other will receive an sensorineural hearing programs with inno- appointment in the 17 loss. vative ideas. The task first three weeks Dayton Children’s after birth. protocol hearing PCR follow up medical hearing Ravi Elluru, MD, PhD, test hearing test management aid division chief of pediatric ENT, strongly normal negative routine no no supported Dr. Patel’s normal positive frequent recommend +/- no desire to develop a protocol for the early hearing loss negative frequent no yes identification and hearing loss positive frequent recommend yes treatment of CMV- related hearing loss in table 2. Recommendations following evaluation using the newborns. A task force Dayton Children’s protocol was formed to create this protocol (table 1).

21 While the above proto- 2. Universal screening strated a hearing loss As further information col seems very simple of newborns for hear- was recommended. from CMV screening and straightforward, ing was recommended. Because of this rec- programs become the execution of the ommendation, more available, additional 3. Screening of protocol itself is any- instances of congenital management neonates who failed thing but. Obtaining CMV should be identi- strategies will their newborn hearing the initial order for the fied, which should lead better define the test for CMV was referral within the first to earlier therapeutic care of infants with recommended. three weeks of life is intervention for CMV asymptomatic a challenge in itself. 4. Universal CMV patients. It should also congenital CMV Obtaining the saliva screening of all lead to clinical studies, infection with and specimen and PCR newborns was which will better report without hearing loss. at the same time as considered but not evidence-based out- Early identification of the audiology refer- recommended. comes of treatment. children with hearing ral appointment visit loss (whether or not 5. Testing for CMV in Universal screening of keeps the entire testing CMV-infected) permits newborns should use all newborns for CMV and reporting compo- close monitoring of the PCR method with was considered but nents within Dayton hearing function during saliva as the preferred not recommended, but Children’s; this avoids the infant’s critical specimen. as in the decision not logistical problems and stages of language to recommend this for lost reports suffered 6. Early treatment with development. The pregnant women, there by other protocols. antiviral agents showed question of whether also is considerable Communication and significant benefit in CMV-infected infants interest in revisiting this education of parents, management of any with hearing loss decision in the future. community physicians CMV-related hearing should routinely receive and their support staff loss. There was universal antiviral therapy will as well as Dayton agreement in the use hopefully be clarified Because CMV is Children’s staff is of PCR to make a from findings in becoming increasingly essential to the success diagnosis of congenital current investigations. recognized as a causal of the protocol. CMV within the first Only through the factor in a variety of four weeks of life. It will analyses of data from conclusion newborn symptoms, also allow early medical targeted screening for there has been The management of management of CMV CMV infection in infants increasing interest in congenital CMV has if this therapy is who fail their newborn the universal screening been gradually indicated. hearing screens can we of pregnant women evolving as more and better define the utility for the virus. The The medical manage- more is understood of such programs.19 consensus report did ment of CMV-related about this ubiquitous Hopefully, our protocol not recommend univer- hearing loss has shown disease. The recent may further add to sal CMV screening of a great deal of promise recommendations from the knowledge base pregnant women this since antiviral agents an informal consensus of appropriate time but there seems were first introduced report developed by management of to be interest in doing in the 1980s. Drug world experts in the these children. so in the future. selection, dosage, field who attended length of treatment Developing innovative the Fifth International Universal screening and method of delivery programs in an Congenital Cytomeg- for hearing loss in (oral vs. IV) are still in area that is not yet alovirus Conference in newborns was recom- a state of discovery. mature presents an 201518 are an excellent mended. This appears Many previous studies opportunity to make a summary of the current to be a worldwide are anecdotal with significant contribution opinions on this topic. clinical validation of relatively small in that field. The simple Their recommendations a program that was numbers of patients. question posed by were: already in effect in the This of course could be Dr. Patel creates United States. 1. Universal screening corrected in the future that opportunity here of pregnant women Screening for CMV in with larger multicenter at Dayton Children’s. for CMV was not newborns who demon- cooperative studies. recommended. 22 references 10. Johnson J, Anderson in all infected infants. CME questions B, Pass RF. Prevention of J Pediatr. 2018. (epub) 10. CMV is the most 1. Pawelec G, McElhaney maternal and congenital https://doi.org10.1016/j. JE, Aiello ME, et al. cytomegalovirus infec- jpeds.2018.03.062. common infection The impact of CMV tion. Clin Obstet Gyne- in newborns. It infection survival in 18. Rawlingson WD, col. 2012;55(2):221-230. is estimated that older humans. Current Bopanna SB, Fowler Opinions in Immunology. 11. Erenberg A, Lemons KB, et al. Congenital 10-12 percent 2012;24(4):507-511. J, Sia C, et al. Newborn cytomegalovirus in- of children who and infant hearing loss: fection in pregnancy contract congenital 2. Cook CH. Cytomeg- Detection and interven- and the neonate: Con- CMV will develop alovirus reactivation tion. American Academy sensus, recommen- some degree of in immunocompetent of Pediatrics: task force dation for prevention, hearing loss by the patients: A call for on infant and newborn diagnosis and therapy. scientific prophylax- hearing. Pediatrics. Lancet Infect Dis. 2017 time they are in is. Journal Infect Dis. 1999;103(2):527-530. Jun;17(6):e177-e188. elementary school. 2007;196(9):1273-1275. doi: 10.1016/S1473- 12. Ross SA, Novak Z, a. True 3. Britt WJ. Congenital 3099(17)30143-3. Epub Pati S, Boppana SB. 2017 Mar 11. b. False human cytomegalovi- Overview of the diag- rus infection and the nosis of cytomegalovi- 19. Vancor E, Shapiro 11. A licensed enigma of maternal rus infection. Infectious ED, Loyal J. Results of audiologist must immunity. J Virology. Disorders: Drug Targets. a targeted screening perform a hearing 2017;91(15):e02392-16. 2011;11(5):466-474. program for congenital screening test in the 4. Joseph A, Mahida N, cytomegalovirus infec- newborn nursery 13. Ahmed A. Antivi- tion in infants who fail Clark G, et al. Congen- ral treatment of cyto- in order for it to be ital cytomegalovirus newborn hearing screen- megalovirus infection. ing. J Pediatr Infect Dis certified. infection. Paediatr Child Infectious Discord Drug Health. 2018;28(6): Soc. 2019;28(8):55-59. a. True Targets. 2011;11(5): doi: 10.1093/jpids/pix105. 277-281. 475-503. b. False

5. Boppana SB, Ross SA, 14. Nassetta L, 12. The recommended Fowler KB. Congenital Kimberlin D, Whitley R. author laboratory test cytomegalovirus Treatment of congen- for the rapid infection: Clinical ital cytomegalovirus identification of outcome. Clin Infect infection: Implications CMV in the neonate Dis. 2013;57(suppl for future therapeutic 4):S178-S181. strategies. J Antimi- is: 6. Goderis J, DeLeenheer crobial Chemotherapy. a. cell culture 2009;63(5):862-867. E, Smets K, et al. Hearing b. NASBA method loss and congenital CMV 15. Pasternak Y, et al. Val- c. nucleic acid infection: A systemat- ganciclovir is beneficial ic review. Pediatrics. in children with congen- sequencing 2014;134(5):972-982. ital cytomegalovirus and d. PCR isolated hearing loss. 7. Dahle AJ, Fowler KB, e. shell viral assay Wright JR, et al. Lon- J Pediatr. 2018. (epub) gitudinal investigation https://doi.org/10.1016/j. 13. The preferred of hearing disorders in peds.2018.02.028. Robert method of delivery Goldenberg, MD children with congenital 16. Amir J, Wolf DG, for valganciclovir cytomegalovirus. J Am in the treatment of Levy I. Treatment of Robert Goldenberg, Academy of Audiology. symptomatic congenital MD, is with the CMV-related hearing 2000;11:283-290. cytomegalovirus infec- division of pediatric loss is: 8. Fowler KB, Bopanno tion with intravenous ganciclovir followed ENT at Dayton a. intravenous SB. Congenital cytomeg- Children’s and alovirus (CMV) infection by long term oral val- b. oral professor emeritus, and hearing defect. ganciclovir. European Wright State c. either intravenous Journal of Clinical Virolo- Journal of Pediatrics. or oral gy. 2006;35(2):226-231. 2010;169(9):1061-1067. University. He is past chair of the division d. all of the above 9. Fowler KB. Congen- 17. Ross S, Long S, of otolaryngology ital cytomegalovirus Kimberlin D. Closer at Wright State e. none of the above infection: Audiologic to universal newborn University Boonshoft screening for congen- outcome. Clin Inf Dis. School of Medicine ital cytomegalovirus 2013;57(suppl 4):182-184. and past chief of staff infection but far away at Dayton Children’s. 23 from antiviral therapy Dayton Children’s updates

”We cannot achieve healthier, today and Dayton Children’s our mission of optimal into adulthood.” health for every child officially opens A few of the unique without addressing components built The Child Health Pavilion the struggles they face into The Child Health every day, like lack Pavilion in addition to Dayton Children’s home, behavioral health of food, substandard the innovative prima- officially opened The and specialty clinical housing or even having ry care medical home Child Health Pavilion on services for vulnerable the right school include: Monday, May 20, 2019, populations (children supplies,” says Deborah reinventing the path to in foster/kinship care, A. Feldman, president • A teaching kitchen children’s health care children with medical and CEO of Dayton where families can for families in our re- complexities, children Children’s Hospital. learn and practice gion and beyond. This with weight issues) ”We envisioned The preparing nutritious new space will support alongside communi- Child Health Pavilion and tasty recipes. a truly unique, integra- ty-based programs as a place to not only tive model of pediatric to address the social elevate what happens • The Food Pharm primary care excellence determinants of health in the doctor’s office where, in partner- unlike anything seen such as food insecuri- but to bridge the gap ship with the Dayton across the country. ty, housing instability, to accessing the Foodbank, families durable goods and social services that will in need can get The new and innovative educational resources help our children be emergency boxes of care model integrates for children. nutritious food. a primary care medical 24 24 • The Family Resource national organizations Connection where and agencies. No one advocates connect group could bring families with an about the level of identified social need change necessary to the appropriate to truly impact the community resources, course of our children’s including food, hous- overall health. “We are ing, transportation, incredibly fortunate to after-school care or be blessed with a baby supplies. community that is rallying around our None of the work at children and a Gov- The Child Health ernor who has made Pavilion could be done children a key priority without collaboration of his agenda,” says and partnership with Feldman. local, state and even

new options for faster, easier care for broken bones and sports injuries

after-hours ortho open scheduling A parent’s first During the day, parents stop may be the or referring doctor’s emergency department offices can get an if they suspect their appointment quickly teen or child has a with convenient online broken bone but scheduling. Simply log Dayton Children’s on and find an open after-hours ortho will time slot, selecting save them time and from multiple days, money. At the south times, providers and campus in Springboro, locations. orthopaedic specialists will be available evenings and weekends hours to diagnose and then Monday – Thursday cast, splint or brace 5:00 pm - 9:00 pm the injury, as needed. Saturday Injuries are never convenient but Not only does this save 7:00 am – 11:00 am Dayton Children’s Hospital is making a family the expense of an emergency sure that treating those injuries is department co-pay, location as painless as possible. There are now but it combines what is normally two visits Specialty care center more options than ever before to better into one. X-rays are Dayton Children’s — care for kids with broken bones or also conveniently south campus sports injuries. available onsite. To avoid a wait, parents 3333 West Tech Road Miamisburg, Ohio can save their spot by checking in online.

25 Dayton Children’s Hospital named one of U.S. News & World Report 2019-20 Best Children’s Hospitals

U.S. News & World one of just 120 Cystic “Without centers like says Deborah Feldman, Report, the global Fibrosis Foundation- this one, trained and president and CEO of authority in hospital accredited care centers accredited in CF care, Dayton Children’s rankings and consumer providing expert care the life expectancy of Hospital. “While we advice, has ranked and specialized disease a child with CF was know it is just one Dayton Children’s management across around elementary measure that a family Hospital in pulmonolo- the country. The net- school age. Now should use in choosing gy in the new 2019-20 work combines clinical people with CF are the right care for their Best Children’s research with medical thriving into adulthood child, it’s another Hospitals rankings care best practices, and and have hope for a symbol parents can published online. has been cited by the healthy future. That use to show them that National Institutes of we have one of these Dayton Children’s “We are proud to be Health as a model of centers right HERE in provides expert care.” recognized by U.S. effective and efficient Dayton is bigger than I News and World “The Best Children’s health care delivery for can say. Caroline will go Report Best Children’s Hospitals rankings a chronic disease. to a center like this for Hospital for the expert were designed to help a check-up every three specialty pediatric care “This center has provide families seek- months for the rest of in pulmonology we honestly changed ing the best medical her life.” provide,” says Daniel our lives,” says Holly care for their sick child Evans, MD, chief, Williams. Her daughter, Dayton Children’s also with access to the most division of pulmonolo- Caroline was diagnosed created the Dayton comprehensive data gy at Dayton Children’s. within days of her birth Asthma Alliance, a available,” said Ben “Our team works hard with cystic fibrosis. group of more than 20 Harder, managing edi- to go above and Excess mucus in her community agencies tor and chief of health beyond for each child, lungs and intestines working in partnership analysis at U.S. News. ensuring they and their makes it hard for her in a global strategy “The rankings, coupled families have the very to breath, digest food to address asthma with guidance from best care in a personal- and leaves her very triggers in a child’s pediatricians, help ized plan that works for susceptible to entire environment— families make better- their unique needs.” infections and illness. where they live, informed decisions She takes a variety of learn and play. about where to Dayton Children’s medications and does find high-quality, pulmonology “The number one breathing treatments compassionate care department is a reason that children several times a day to for their children when Cystic Fibrosis Center, are admitted to Dayton shake the mucus from they need it most.” Children’s Hospital is her lungs. for respiratory issues,”

26 program evaluation program test

1. The material presented in this publication met to obtain CME credit you must: the mission to enhance health care delivery Read and reflect on each article. in our region through education based on the essentials and policies of the Accreditation Answer the questions from each article and complete Council for Continuing Medical Education. this test. 70 percent correct answers are needed to c Strongly agree c Agree c Neutral obtain the full 4.0 AMA PRA Category 1 CreditsTM. c Disagree c Strongly disagree Complete the program evaluation. Return your completed test and program evaluation by 2. Did the material presented in this publication meet the educational objectives stated? email, mail or fax to: Sue Strader, coordinator Department of Continuing Medical Education c Yes c No Dayton Children’s Hospital, One Children’s Plaza, Dayton, Ohio 45404-1815 3. Did the material presented in this publication Fax: 937-641-5931 have a commercial bias? c Yes c No E-mail: [email protected] Take test online: childrensdayton.org/providers 4. Please rate the contents of this issue using the following scale: This test must be received by December 31, 1 = Poor, 2 = Fair, 3 = Good, 4 = Very good, 2019 for the credit to be awarded 5 = Excellent (Circle one response for each.) Poor Excellent Timely, up-to-date? 1 2 3 4 5 Practical? 1 2 3 4 5 pediatric forum | volume 33, issue 2 Relevant to your practice? 1 2 3 4 5 your answers to CME questions 5. Please describe any changes you plan to (Please circle the BEST answer.) make in your clinical practice based on the 1. true false information presented in this program. 2. true false 3. true false ______4. a b c d e 5. true false 6. Are there any other topics you would like 6. a b c d e to have addressed in this publication or future educational programs for health 7. true false care providers? 8. true false c Yes c No If yes, please describe: 9. true false 10. true false ______11. true false 12. a b c d e 7. Please describe how you will incorporate information obtained from this publication 13. a b c d e into your practice. please type or print clearly ______name______8. Letter to the editor — Letter to the editor practice name______may be emailed to [email protected] or attached to this evaluation and may street address______be published in the next issue. city______

physician accreditation statement and credit designation state/zip code______This activity has been planned and implemented in accordance office telephone______with the Essential Areas and Policies of the Accreditation Council for Continuing Medical Education (ACCME) through office fax______the joint providership of Wright State University (WSU) and Dayton Children’s Hospital. e-mail______WSU designates this Journal-based CME Activity for a maximum of 4 AMA PRA Category 1 Credit(s)™. Physicians signature______should claim only the credit commensurate with the extent 27 of their participation in the activity. physician accreditation sponsorship/accreditation information pediatric statement and credit forum designation summer 2019 This activity has author information Kristin Mikolajewski, MSN, been planned and CPNP-AC/PC It is the policy of Wright [email protected] implemented in State University to ensure balance, independence, Ms. Mikolajewski has One Children’s Plaza accordance with the objectivity and scientific nothing to disclose with Dayton, Ohio Essential Areas and rigor in all educational regard to commercial 45404-1815 Policies of the activities. support. 937-641-3000 Accreditation Council All authors contributing Ms. Mikolajewski does childrensdayton.org for Continuing Medical to our programs are notplan on discussing expected to disclose any unlabeled/investigational Education (ACCME) relationships they may uses of a commercial through the joint have with commercial product. Pediatric Forum providership of Wright companies whose products or services may Lora Scott, MD is produced for the State University (WSU) [email protected] professional staff and be mentioned so that and Dayton Children’s participants may evaluate Dr. Scott has nothing referring physicians Hospital. the objectivity of the to disclose with regard of Dayton Children’s program. In addition, to commercial support. any discussion of by the marketing WSU designates this off-label, experimental Dr. Scott does not plan communications Journal-based CME or investigational use of on discussing unlabeled/ department. drugs or devices will be investigational uses of a Activity for a maximum disclosed by the authors. commercial product. of 4 AMA PRA Category Contributing authors reported the following: Robert Goldenberg, MD The purpose of 1 Credit(s)™. Physicians [email protected] Pediatric Forum is to should claim only the Lubabatu Abdurrahman, provide information credit commensurate MD, FACC Dr. Goldenberg has nothing [email protected] to disclose with regard to and news about with the extent of their commercial support. pediatric health care participation in the Joseph Ross, MD, FACC [email protected] Dr. Goldenberg does issues and to provide activity. not plan on discussing information about Drs. Abdurrahman and unlabeled/investigational Ross have nothing to uses of a commercial clinical services and obtaining CME credit disclose with regard to product. management issues of commercial support. To obtain CME credit, Dayton Children’s. Drs. Abdurrahman and read, reflect on Ross do not plan on articles, complete discussing unlabeled/ editorial/board the evaluation and investigational uses of a commercial product. Sherman Alter, MD answer at least 70 editor percent of the quiz Lucinda Brown, MSN, RN, CNS correctly. Send the Lisa Coffey, FACHE answer sheet and L. David Mirkin, MD program evaluation to: The content and views presented are those of the author and do Kelly Sandberg, MD not necessarily reflect those of the publisher, Dayton Children’s. Unlabeled use of products may be mentioned. Before prescribing Sue Strader, any medicine, primary references and full prescribing information coordinator should be consulted. All planning committee members have disclosed that they do not have any financial relationships with Sherman Alter, MD department of director, continuing medical education commercial entities that may impact the content of this publication. continuing medical Deborah A. Feldman education target audience president and chief executive officer Dayton Children’s Adam G. Mezoff, One Children’s Plaza This education activity is designed for MD, CPE, AGAF Dayton, OH 45404-1815 pediatricians, family physicians and related vice president for health care Fax 937-641-5931 child health care providers. transformation, medical affairs Email straders@ chief medical officer childrensdayton.org educational objectives Matthew Hardwick, MD • Identify the four pediatric issues covered in this chair of the professional staff Take quiz online: journal and develop appropriate intervention. childrensdayton.org/ • Appropriately use the resources of Dayton providers Children’s Hospital to improve patient care.

The answer sheet and program evaluation must be received by December 31, 2019, for the credit to be awarded.

28 Dayton Children’s Hospital One Children’s Plaza Dayton, Ohio 45404-1815 EP8658 © 2019 Dayton Children’s Hospital. All Rights Reserved. The Whirligig, Logo Mark Logo Whirligig, The Hospital. All Rights Reserved. Children’s Dayton EP8658 © 2019 Hospital • childrensdayton.org Children’s Dayton by owned are and all trademarks

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