Ms. Hester is Content Specialist with Contemporary OB/GYN and Contemporary Pediatrics.

Miranda Hester

The news is full of stories about monkeypox, the recent changes to COVID-19 guidance, and the return of polio cases. What do clinicians need to know?



 sat down with its editor-in-chief, Tina Q. Tan, MD, FAAP, FIDSA, FPIDS, to discuss the what families can do to prevent polio, the most current information on monkeypox in pediatrics, and the new guidance from the Centers for Disease Control and Prevention on COVID-19.

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The news is full of stories about monkeypox, the recent changes to COVID-19 guidance, and the return of polio cases. What do clinicians need to know?

What's going on with polio, monkeypox, and COVID-19

 evokes images of early adolescence and for most children, that is when they transition to this next stage of growth. However, some children who are going through central precocious puberty (CPP) will enter puberty earlier than their peers, in some cases much earlier. In a webinar from the 

 series, 2 experts discussed a variety of subjects on CPP, including findings from a recent study that examined treatment initiation and duration with height, the need to individualize treatment decisions for girls with CPP, and 2 case reports.

 Karen O. Klein, MD, a pediatric endocrinologist at Rady Children’s Hospital-San Diego in California and an associate clinical professor of pediatrics at the University of California San Diego School of Medicine, led the discussion with Kent L. Reifschneider, MD, a pediatric endocrinologist at Children’s Hospital of The King’s Daughters in Norfolk, Virginia.

CPP occurs when the hypothalamic-pituitary-gonadal axis is activated early on, which leads to an increase in gonadal steroid hormone secretion. The ages of affected children are less than 8 years for girls and less than 9 years for boys. Children affected by CPP develop secondary characteristics early on; have at least 1 Tanner stage progression per year; and have less than 2 standard deviations in bone age (BA) beyond chronological age (CA). If untreated, CPP can lead to early fusing of growth plates, a reduction in adult stature, atypical pubertal physical development, and premature menarche. Gonadotropin-releasing hormone agonists are the standard-of-care treatment.

Klein discussed her recent study coauthored with Marcela Vargas Trujillo, MD; Sanja Dragnic, MD; and Petra Aldridge, MS. The authors performed the investigation to supply data for an area in which data were scarce: the benefit to height outcomes when treatment with leuprolide was initiated after CA of 7 years and continued after CA of 10 years or BA of 12 years. The study was carried out in 48 treatment-naïve girls who were treated with monthly leuprolide, administered intramuscularly every 28 days at doses based on weight. The investigators only included girls so that the results would have statistical power. The patients had visits at weeks 4, 8, 12, 24, 36, and 48 and then every 6 months until leuprolide was discontinued. They then had annual visits until age 21 years. The average treatment duration was 3.9 plus/minus 2.0 years (range, 1.1-9.8). The average CA at the end of treatment was 11.5 plus/minus 0.97 years (range, 9.8-14.1) whereas the average BA was 12.7 plus/minus 0.94 years (range, 11.5-16.4). Throughout the treatment period, the ratio of BA to CA consistently decreased. Fifteen girls achieved a BA that was less than 1 year above the CA. Longer duration of treatment was associated with increased predicted adult height for nearly all the girls, 45 of 48. Those who saw no improvement were either near midparental height when they started the treatment or showed poor growth velocity. A wide range was found in final heights: 162.54 plus/minus 7.35 cm (range, 146.47-176.11) that was similar to the predicted adult height in treatment (162.39 ± 8.38 cm). Midparental height was not available for all the girls, but of the 29 for whom it was available, 17 either met or surpassed it.

Reifschneider joined Klein to discuss nuances in the treatment of CPP. He noted, “With CPP, I think of the limitations of the disease state, which includes the impact of estrogen on growth velocity and BA and how much that should factor into clinical decisions as well as the variability in interpreting BA.”

Klein added, “When examining a patient, a clinician should balance the need for more data with the fact that early commencement of treatment can lead to better height outcomes.” She also noted that estimating predicted adult height is also mostly based on average-sized children who are having average growth patterns. Another consideration for starting treatment is the predicted adult height of the patient and the height of the child’s parents. For example, if the predicted height for a child is 155 cm and the mother is 157.5 cm, treatment may not be considered necessary by the patient’s family.

Klein added that although treatment will pause the tempo of puberty, once treatment ends, the tempo will resume its speed. However, this does not mean that a pubertal growth spurt will occur, and, in fact, data indicate that this typically doesn’t occur. 

The first case Reifschneider and Klein examined concerned a girl, with the following details:

Tanner stage 3 breast development, starting at age 7 years

With the girl’s BA and current height, her predicted final height is roughly 147 cm and her midparental height, 168 cm. The BA maturation was noted as significant by Reifschneider and the patient would meet his criteria for treatment. However, Klein emphasized the patient’s age, noting that she had been trained to only treat children when pubertal onset occurred before age 8 years. Countering that assertion, Reifschneider said, “One has to keep in mind the individual and that a lab [finding] or CA is just a piece of the puzzle. In this case, the fact that the girl started developing breast tissue when she was aged 7 years is important, in addition to growth velocity that is greater than prepubertal [velocity] as well as bones that are considerably advanced.”

When discussing treatment with families, a conversation about outcomes can be important. Many girls with CPP can be among the tallest girls in their class but their BA is often much advanced, and when their non-CPP peers reach puberty, many affected girls will be left behind in terms of height. If he were treating this patient, Reifschneider said, he would ideally initiate treatment and then see her every 4 to 6 months to determine how the treatment has changed the tempo of her puberty. Once the tempo became prepubertal, he would transition to twice yearly maintenance screenings.

The second case was of a girl with CPP who had undergone treatment, with the following details:

Leuprolide acetate treatment initiated at age 6 years

1 incidence of vaginal bleeding following treatment initiation

Tanner stage 3 breast development at age 6 years

The patient’s breast development has stabilized at Tanner stage 3. Her BA is 12 years and her height is currently predicted to reach 60 cm. She is now asking whether it’s time to stop treatment.

Reifschneider emphasized that this was a very successful case and the patient had responded very well to therapy. “When considering the ceasing of treatment, there are a couple of things that need to be thought through, like the limitation of predicted adult heights and not knowing the tempo that will occur when she ceases treatment. Although she is currently predicted to reach 5 feet, there is a likelihood that she would not achieve that height if she ended treatment.” Klein added that a BA of 12 years has often been considered the end point for treatment because of questions about whether continued growth could be achieved, but her study findings showed that 5 to 10 additional cm can be achieved with continued treatment. Reifschneider confirmed that prior to publication of the study’s results, he would have considered ending treatment at BA 12, although he noted that this patient was an outlier who likely would continue to benefit from treatment.

1. Klein KO, Reifschneider K. Between the lines: central precocious puberty. Virtual webinar. Recorded March 4, 2022.

Articles

Two experts discuss a variety of subjects on central precocious puberty, including recent study findings that examined treatment initiation and duration with height, the need to individualize treatment decisions for girls with CPP, and 2 case reports. 

Between the lines: central precocious puberty

Neck floats are marketed to parents and caregivers for a variety of uses, from swimming to being used as a physical therapy tool for water therapy in infants with developmental delays or disabilities. Some manufacturers even market them for use with infants as young as 2 weeks of age. Therapeutic claims include improved lung capacity, increased muscle tone, and greater range of motion. However, the US Food and Drug Administration (FDA) has issued a Safety Communication warning parents and caregivers that using them for water therapy can lead to serious injury or death in infants with spina bifida, spinal muscular atrophy, type 1, cerebral palsy, or other neurodevelopmental conditions. The communication offers recommendations for both parents and health care providers.

Awareness that using a neck float with an infant who had special needs could potentially increase the risk of neck strain and injury.

Know that neck floats have not been evaluated by the FDA and no demonstrated benefit has been seen with their use.

Do not use neck floats for water therapy.

 any injury caused by a neck float to the FDA.

The communication made the following recommendations for clinicians:

Go over the safety communication with staff, colleagues, and parents during well-child visits.

Offer clear discouragement for using neck floats in infants with special needs.

Encourage parents who experience injury or death because of neck float use to report it to the FDA.

The communication is the result of 2 known cases of injury or death due to use of the device. Both cases occurred when the infant was not directly monitored. Additionally, the therapeutic claims made by manufacturers has been made without clearance from the agency. Companies who made these claims have been informed of the FDA’s concerns and future marketing will be monitored.

Do not use baby neck floats due to the risk of death or injury: FDA safety communication. US Food and Drug Administration. Published June 28, 2022. Accessed June 29, 2022. 

https://www.fda.gov/medical-devices/safety-communications/do-not-use-baby-neck-floats-due-risk-death-or-injury-fda-safety-communication

The US Food and Drug Administration (FDA) has issued a safety communication warning about the risk of serious injury or death associated with neck floats when used for water therapy in babies with special needs.

FDA issues warning for neck floats used for water therapy

When in-person learning returned for many students, one of the most common ways to prevent the spread of COVID-19 in schools was for schools to close if a specific number of staff and students became sick with the disease or, in some cases, if the community spread reached a certain level. Such school closures not only disrupted the education of affected children, but could keep children from accessing the resources necessary to thrive. An 

 examines whether the use of targeted approaches could be just as effective as school closures to reduce infection rates.

The investigators compared the infection rates in grades 1-10 in schools in 7 boroughs in Oslo, Norway from February 15, 2021 to April 18, 2021. All of the schools utilized strict targeted approaches, but schools were closed as required for students in grades 5 to 10. Nationwide registries were used to collect information.

A positive COVID-19 test was obtained for 616 students in grade 1-4, 452 in grades 5-7, and 446 in grades 8-10 during the study period. The Alpha variant was the predominant variant circulating at the time. The investigators found a statistically significant reduction in the post-intervention trends seen in grades 1-4 (coef -1.26, 95%CI -2.44 to -0.09). Furthermore, they found no difference in the trends between grades 1-4 and 5-7 (coef 0.66, 95%CI -1.25 to 2.58) nor between grades 1-4 and 8-10 (coef -0.63, 95%CI -2.30 to 1.04).

The investigators concluded that school closures were no more efficacious at reducing the rate of student infections than using targeted measures. The findings suggest that the use of just strict mitigation measures such as rigorous adherence to social distancing or masking could be an effective way to keep children safe without disrupting their education. 

1. Rotevatn T, Elstrøm P, Greve-Isdahl M, Surén P, Johansen T, Astrup E. School closure versus targeted control measures for SARS-CoV-2 infection. 

. March 11, 2022. Epub ahead of print. doi: 10.1542/peds.2021-055071

School closures have been the go-to move to prevent the spread of COVID-19, but a report investigates whether the use of strict mitigation can work just as well without the need to disrupt a child’s in-person schooling.

Can strict mitigation work as well as closure to reduce the spread of COVID-19?

Not all emergency departments have the staff and equipment necessary to provide optimal care to children. A 

 examines whether a high degree of readiness for pediatric patients in hospital emergency departments is linked to an improvement in the long-term outcomes for children who are treated in them.

Investigators ran a retrospective cohort study that examined injured children aged younger than 18 years who lived in 8 states and had either admission, transfer to, or injury-related death at 1 of 146 trauma centers that were participated. Children were included in the study, regardless of whether treatment occurred in their state of residence. They created subgroups for children such as Injury Severity Score (ISS) of 16 or more; any Abbreviated Injury Scale (AIS) score of 3 or more; head AIS score of 3 or more; and need for early critical resources. Data were from January 2012 to December 2017 and follow-up occurred through December 2018. The initial readiness of the emergency departments was assessed using the weighted Pediatric Readiness Score (range, 0-100) from the 2013 National Pediatric Readiness Project assessment.

There were 88,071 children included in the study who had a median age of 11 years. The investigators found that 1974 of them died within a year of the first emergency department visit, which included 1768 who died during the course of hospitalization and 206 who died after being discharged. The subgroups included 12,752 (14.5%) with an ISS of 16 or more, 28 402 (32.2%) with any AIS score of 3 or more, 13,348 (15.2%) with a head AIS of 3 or more, and 9048 (10.3%) requiring early critical resources. When compared to emergency departments in the lowest weighted Pediatric Readiness Score quartile, children who were cared for in emergency departments in the highest quartile had lower hazard of death to 1 year (adjusted hazard ratio, 0.70; 95% CI, 0.56-0.88).

The investigators concluded that being treated in a trauma center emergency department with a high degree of readiness was linked to a lower risk of death that lasted to 1 year. Furthermore, a high level of readiness was independently linked to long-term survival among children with injuries. The findings continue to confirm that care tailored to children’s needs leads to better outcomes.

Newgard C, Lin A, Goldhaber-Fiebert J, et al. Association of emergency department pediatric readiness with mortality to 1 year among injured children treated at trauma centers. 

. February 2, 2022.Epub ahead of print. doi:10.1001/jamasurg.2021.7419

Does readiness to treat pediatric patients in the emergency department lead to less mortality in the year following presentation? An investigation offers answers.

Does the readiness of emergency services impact mortality?

With the COVID-19 pandemic reaching an unprecedented crescendo and pediatric cases continuing to become more prominent with each new variant of the disease, an understanding of how many pediatric cases that initially present and receive testing in an emergency department experience a severe outcome or death is more important than ever. A 

 aims to find the proportion of pediatric patients who experience such outcomes within 14 days.

Investigators performed a prospective cohort study with 14-day follow-up that enrolled participants between March 2020 and June 2021. They included children and adolescents aged younger than 18 years who were tested for COVID-19 infection at an emergency department in 10 countries: Argentina, Australia, Canada, Costa Rica, Italy, New Zealand, Paraguay, Singapore, Spain, and the United States. Infection was confirmed via a polymerase chain reaction test. Severe outcomes were either the occurrence of a complication such as encephalitis or cardiac arrest or the performance of an intervention linked to a severe occurrence such as chest drainage or positive pressure ventilation, as well as death.

There were 3221 patients included in the study, with 2007 coming from the United States and 484 self-reporting a chronic illness. The median age of the cohort was 3 years. Following 14 days of follow-up, 735 children required hospitalization; 107 recorded severe outcomes; and 4 children had died. Investigators noted that there were several characteristic that were linked to severe outcomes, including being aged 5 to 18 years (age 5 to <10 years vs <1 year: odds ratio [OR], 1.60 [95% CI, 1.09-2.34]; age 10 to <18 years vs <1 year: OR, 2.39 [95% CI 1.38-4.14]), having a self-reported chronic illness (OR, 2.34 [95% CI, 1.59-3.44]), prior episode of pneumonia (OR, 3.15 [95% CI, 1.83-5.42]), symptoms starting 4 to 7 days prior to seeking ED care (vs starting 0-3 days before seeking care: OR, 2.22 [95% CI, 1.29-3.82]), and country (eg, Canada vs US: OR, 0.11 [95% CI, 0.05-0.23]; Costa Rica vs US: OR, 1.76 [95% CI, 1.05-2.96]; Spain vs US: OR, 0.51 [95% CI, 0.27-0.98]). In a subcohort of patients who were sent home from the emergency department after being tested and completed the 14 days of follow-up, 50 were subsequently hospitalized and 12 had severe outcomes.

The investigators concluded that about 3% of pediatric patients who tested positive for COVID-19 in the emergency department had severe outcomes within 2 weeks of their initial visit. The risk was much less for children who were sent home from the emergency department than among those who were kept in the hospital. The risk factors noted such as age and underlying chronic illness could be useful when determining a patient’s clinical care.

Funk A, Florin T, Kupperman N, et al. Outcomes of SARS-CoV-2–positive youths tested in emergency departments: the global PERN–COVID-19 study. 

. 2022;5(1):e2142322. doi:10.1001/jamanetworkopen.2021.42322

A global study examines how often severe outcomes occur within 14 days of a positive COVID-19 test occurring in an emergency department (ED).