PEDIATRICS recent issues

Fertility Preservation Outcomes in Adolescent and Young Adult Feminizing Transgender Patients

BACKGROUND:

Fertility preservation enables patients undergoing gonadotoxic therapies to retain the potential for biological children and now has broader implications in the care of transgender individuals. Multiple medical societies recommend counseling on fertility preservation before initiating therapy for gender dysphoria; however, outcome data pre- and posttreatment are limited in feminizing transgender adolescents and young adults.

METHODS:

The University of Pittsburgh Institutional Research Board approved this study. Data were collected retrospectively on transgender patients seeking fertility preservation between 2015 and 2018, including age at initial consultation and semen analysis parameters.

RESULTS:

Eleven feminizing transgender patients accepted a referral for fertility preservation during this time; consultation occurred at median age 19 (range 16–24 years). Ten patients attempted and completed at least 1 semen collection. Eight patients cryopreserved semen before initiating treatment. Of those patients, all exhibited low morphology with otherwise normal median semen analysis parameters. In 1 patient who discontinued leuprolide acetate to attempt fertility preservation, transient azoospermia of 5 months’ duration was demonstrated with subsequent recovery of spermatogenesis. In a patient who had previously been treated with spironolactone and estradiol, semen analysis revealed persistent azoospermia for the 4 months leading up to orchiectomy after discontinuation of both medications.

CONCLUSIONS:

Semen cryopreservation is a viable method of fertility preservation in adolescent and young adult transgender individuals and can be considered in patients who have already initiated therapy for gender dysphoria. Further research is needed to determine the optimal length of time these therapies should be discontinued to facilitate successful semen cryopreservation.

Testing for Meningitis in Febrile Well-Appearing Young Infants With a Positive Urinalysis

BACKGROUND AND OBJECTIVES:

To determine factors associated with cerebrospinal fluid (CSF) testing in febrile young infants with a positive urinalysis and assess the probability of delayed diagnosis of bacterial meningitis in infants treated for urinary tract infection (UTI) without CSF testing.

METHODS:

We performed a retrospective cohort study using data from the Reducing Excessive Variability in Infant Sepsis Evaluation quality improvement project. A total of 20 570 well-appearing febrile infants 7 to 60 days old presenting to 124 hospitals from 2015 to 2017 were included. A mixed-effects logistic regression was conducted to determine factors associated with CSF testing. Delayed meningitis was defined as a new diagnosis of bacterial meningitis within 7 days of discharge.

RESULTS:

Overall, 3572 infants had a positive urinalysis; 2511 (70.3%) underwent CSF testing. There was wide variation by site, with CSF testing rates ranging from 64% to 100% for infants 7 to 30 days old and 10% to 100% for infants 31 to 60 days old. Factors associated with CSF testing included: age 7 to 30 days (adjusted odds ratio [aOR]: 4.6; 95% confidence interval [CI]: 3.8–5.5), abnormal inflammatory markers (aOR: 2.2; 95% CI: 1.8–2.5), and site volume >300 febrile infants per year (aOR: 1.8; 95% CI: 1.2–2.6). Among 505 infants treated for UTI without CSF testing, there were 0 (95% CI: 0%–0.6%) cases of delayed meningitis.

CONCLUSIONS:

There was wide variation in CSF testing in febrile infants with a positive urinalysis. Among infants treated for UTI without CSF testing (mostly 31 to 60-day-old infants), there were no cases of delayed meningitis within 7 days of discharge, suggesting that routine CSF testing of infants 31 to 60 days old with a positive urinalysis may not be necessary.

Abdominal Pain and Intermittent Fevers in a 16-Year-Old Girl

A 16-year-old girl presented to the emergency department with intermittent fevers and worsening abdominal pain of 5 weeks duration. She had a history of travel to a less developed country and exposure to possible infectious diseases. Abdominal imaging and blood tests revealed diffuse mesenteric lymphadenopathy, elevated transaminases, and elevation of inflammatory markers. Gastroesophageal and colon endoscopies revealed gastric ulcers, and the patient was discharged with a presumptive diagnosis of systemic juvenile idiopathic arthritis given the lymphadenopathy seen on imaging, serositis, sacroiliac joint stiffness noted on physical examination, and pain relief with celecoxib. She presented again 4 days later with worsening abdominal tenderness, elevated transaminases, and new-onset abdominal distention. Tissue biopsy yielded the diagnosis and directed appropriate treatment.

Does It Matter if This Baby Is 22 or 23 Weeks?

A 530-g girl born at 22 weeks and 6 days’ gestation (determined by an ultrasound at 11 weeks) was admitted to the NICU. Her mother had received prenatal steroids. At 12 hours of age, she was stable on low ventilator settings. Her blood pressure was fine. Her urine output was good. After counseling, her parents voiced understanding of the risks and wanted all available life-supporting measures. Many nurses were distressed that doctors were trying to save a "22-weeker." In the past, 4 infants born at 22 weeks’ gestation had been admitted to that NICU, and all had died. The attending physician on call had to deal with many sick infants and the nurses’ moral distress.

Prenatal Opioid Exposure: Neurodevelopmental Consequences and Future Research Priorities

Neonatal opioid withdrawal syndrome (NOWS) has risen in prevalence from 1.2 per 1000 births in 2000 to 5.8 per 1000 births in 2012. Symptoms in neonates may include high-pitched cry, tremors, feeding difficulty, hypertonia, watery stools, and breathing problems. However, little is known about the neurodevelopmental consequences of prenatal opioid exposure in infancy, early childhood, and middle childhood. Even less is known about the cognitive, behavioral, and academic outcomes of children who develop NOWS. We review the state of the literature on the neurodevelopmental consequences of prenatal opioid exposure with a particular focus on studies in which NOWS outcomes were examined. Aiming to reduce the incidence of prenatal opioid exposure in the near future, we highlight the need for large studies with prospectively recruited participants and longitudinal designs, taking into account confounding factors such as socioeconomic status, institutional variations in care, and maternal use of other substances, to independently assess the full impact of NOWS. As a more immediate solution, we provide an agenda for future research that leverages the National Institutes of Health Environmental Influences on Child Health Outcomes program to address many of the serious methodologic gaps in the literature, and we answer key questions regarding the short- and long-term neurodevelopmental health of children with prenatal opioid exposure.

Parenteral Antibiotic Therapy Duration in Young Infants With Bacteremic Urinary Tract Infections

OBJECTIVES:

To determine the association between parenteral antibiotic duration and outcomes in infants ≤60 days old with bacteremic urinary tract infection (UTI).

METHODS:

This multicenter retrospective cohort study included infants ≤60 days old who had concomitant growth of a pathogen in blood and urine cultures at 11 children’s hospitals between 2011 and 2016. Short-course parenteral antibiotic duration was defined as ≤7 days, and long-course parenteral antibiotic duration was defined as >7 days. Propensity scores, calculated using patient characteristics, were used to determine the likelihood of receiving long-course parenteral antibiotics. We conducted inverse probability weighting to achieve covariate balance and applied marginal structural models to the weighted population to examine the association between parenteral antibiotic duration and outcomes (30-day UTI recurrence, 30-day all-cause reutilization, and length of stay).

RESULTS:

Among 115 infants with bacteremic UTI, 58 (50%) infants received short-course parenteral antibiotics. Infants who received long-course parenteral antibiotics were more likely to be ill appearing and have growth of a non–Escherichia coli organism. There was no difference in adjusted 30-day UTI recurrence between the long- and short-course groups (adjusted risk difference: 3%; 95% confidence interval: –5.8 to 12.7) or 30-day all-cause reutilization (risk difference: 3%; 95% confidence interval: –14.5 to 20.6).

CONCLUSIONS:

Young infants with bacteremic UTI who received ≤7 days of parenteral antibiotics did not have more frequent recurrent UTIs or hospital reutilization compared with infants who received long-course therapy. Short-course parenteral therapy with early conversion to oral antibiotics may be considered in this population.

Electronic Nicotine Delivery Systems Marketing and Initiation Among Youth and Young Adults

BACKGROUND AND OBJECTIVES:

Electronic nicotine delivery systems (ENDS) have become the most popular tobacco products among young people, yet ENDS marketing remains unregulated, and its effects on ENDS use behavior across age groups is poorly understood. In this study, using a longitudinal design, we examined how recall of ENDS marketing through 5 different channels predicted subsequent ENDS initiation up to 2.5 years later among youth (ages 12–17 years) and young adults (ages 18–29 years).

METHODS:

Data were drawn from 2 large cohort studies in Texas. The analysis included school-going youth (n = 2288) and college-going young adults (n = 2423) who reported never having used ENDS at baseline in 2014. Logistic regression was used to assess the influence of recalled ENDS marketing exposure via television (TV), radio or Internet radio, billboards, retail stores, and the Internet on subsequent ENDS initiation, with adjustment for these channels, baseline sociodemographics, other past-30-day tobacco use, sensation seeking, and peer ENDS use.

RESULTS:

Recall of retail store–based ENDS marketing at baseline was associated with significantly higher odds of subsequent ENDS initiation among youth (adjusted odds ratio [aOR] = 1.99; 95% confidence interval [CI]: 1.25–3.17) and young adults (aOR = 1.30; 95% CI: 1.05–1.61) up to 2.5 years later. Young adult initiation was also associated with recalled ENDS marketing on TV at baseline (aOR = 1.29; 95% CI: 1.03–1.63).

CONCLUSIONS:

Marketing of ENDS at retail stores predicts youth and young adult ENDS initiation, and marketing on TV predicts young adult initiation. Future research and regulation should be used to address the most influential marketing channels.

Prednisolone Versus Dexamethasone for Croup: a Randomized Controlled Trial

OBJECTIVES:

The use of either prednisolone or low-dose dexamethasone in the treatment of childhood croup lacks a rigorous evidence base despite widespread use. In this study, we compare dexamethasone at 0.6 mg/kg with both low-dose dexamethasone at 0.15 mg/kg and prednisolone at 1 mg/kg.

METHODS:

Prospective, double-blind, noninferiority randomized controlled trial based in 1 tertiary pediatric emergency department and 1 urban district emergency department in Perth, Western Australia. Inclusions were age >6 months, maximum weight 20 kg, contactable by telephone, and English-speaking caregivers. Exclusion criteria were known prednisolone or dexamethasone allergy, immunosuppressive disease or treatment, steroid therapy or enrollment in the study within the previous 14 days, and a high clinical suspicion of an alternative diagnosis. A total of 1252 participants were enrolled and randomly assigned to receive dexamethasone (0.6 mg/kg; n = 410), low-dose dexamethasone (0.15 mg/kg; n = 410), or prednisolone (1 mg/kg; n = 411). Primary outcome measures included Westley Croup Score 1-hour after treatment and unscheduled medical re-attendance during the 7 days after treatment.

RESULTS:

Mean Westley Croup Score at baseline was 1.4 for dexamethasone, 1.5 for low-dose dexamethasone, and 1.5 for prednisolone. Adjusted difference in scores at 1 hour, compared with dexamethasone, was 0.03 (95% confidence interval –0.09 to 0.15) for low-dose dexamethasone and 0.05 (95% confidence interval –0.07 to 0.17) for prednisolone. Re-attendance rates were 17.8% for dexamethasone, 19.5% for low-dose dexamethasone, and 21.7% for prednisolone (not significant [P = .59 and .19]).

CONCLUSIONS:

Noninferiority was demonstrated for both low-dose dexamethasone and prednisolone. The type of oral steroid seems to have no clinically significant impact on efficacy, both acutely and during the week after treatment.

Scurvy Due to Selective Diet in a Seemingly Healthy 4-Year-Old Boy

Scurvy is a rare disease in developed nations. In the field of pediatrics, it primarily is seen in children with developmental and behavioral issues, malabsorptive processes, or diseases involving dysphagia. We present the case of an otherwise developmentally appropriate 4-year-old boy who developed scurvy after gradual self-restriction of his diet. He initially presented with a limp and a rash and was subsequently found to have anemia and hematuria. A serum vitamin C level was undetectable, and after review of the MRI of his lower extremities, the clinical findings supported a diagnosis of scurvy. Although scurvy is rare in developed nations, this diagnosis should be considered in a patient with the clinical constellation of lower-extremity pain or arthralgias, a nonblanching rash, easy bleeding or bruising, fatigue, and anemia. This case highlights the importance of carefully assessing a child’s dietary and developmental status at well-child visits, which can help avoid a more invasive workup.

Mental Health, Drug, and Violence Interventions for Sexual/Gender Minorities: A Systematic Review

CONTEXT:

Compared with cisgender (nontransgender), heterosexual youth, sexual and gender minority youth (SGMY) experience great inequities in substance use, mental health problems, and violence victimization, thereby making them a priority population for interventions.

OBJECTIVE:

To systematically review interventions and their effectiveness in preventing or reducing substance use, mental health problems, and violence victimization among SGMY.

DATA SOURCES:

PubMed, PsycINFO, and Education Resources Information Center.

STUDY SELECTION:

Selected studies were published from January 2000 to 2019, included randomized and nonrandomized designs with pretest and posttest data, and assessed substance use, mental health problems, or violence victimization outcomes among SGMY.

DATA EXTRACTION:

Data extracted were intervention descriptions, sample details, measurements, results, and methodologic rigor.

RESULTS:

With this review, we identified 9 interventions for mental health, 2 for substance use, and 1 for violence victimization. One SGMY-inclusive intervention examined coordinated mental health services. Five sexual minority–specific interventions included multiple state-level policy interventions, a therapist-administered family-based intervention, a computer-based intervention, and an online intervention. Three gender minority–specific interventions included transition-related gender-affirming care interventions. All interventions improved mental health outcomes, 2 reduced substance use, and 1 reduced bullying victimization. One study had strong methodologic quality, but the remaining studies’ results must be interpreted cautiously because of suboptimal methodologic quality.

LIMITATIONS:

There exists a small collection of diverse interventions for reducing substance use, mental health problems, and violence victimization among SGMY.

CONCLUSIONS:

The dearth of interventions identified in this review is likely insufficient to mitigate the substantial inequities in substance use, mental health problems, and violence among SGMY.

Early Childhood Vaccination Status of Preterm Infants

BACKGROUND:

Preterm infants are at increased risk for vaccine-preventable infections and associated complications. Limited studies describe timely vaccination of these vulnerable infants.

METHODS:

This retrospective cohort study included Washington State infants with birth hospitalizations at an urban academic medical center between 2008 and 2013. Demographic, clinical, and visit data from electronic health records were linked to vaccine data from the Washington State Immunization Information System. Completion of the recommended 7-vaccine series by 19 months of age was compared between preterm infants (born at <37 weeks’ gestation) and term/postterm infants (born at 37–43 weeks’ gestation) by using Pearson’s 2 test and multivariable logistic regression. Secondary outcomes included 7-vaccine series completion by 36 months of age and receipt of individual vaccines in the series. Rotavirus, hepatitis A, and influenza vaccination was also assessed.

RESULTS:

Of study infants (n = 10 367), 19.3% were born prematurely. Preterm infants had lower 7-vaccine series completion compared with term/postterm infants by 19 months (47.5% vs 54.0%; adjusted odds ratio 0.77 [95% confidence interval 0.65–0.90]) and 36 months (63.6% vs 71.3%; adjusted odds ratio 0.73 [95% confidence interval 0.61–0.87]). Early preterm (23–33 weeks’ gestation) and late preterm (34–36 weeks’ gestation) infants had a lower rate of 7-vaccine series completion compared with term/postterm infants. Full influenza vaccination coverage by 19 months also differed between groups (early preterm: 47.7%; late preterm: 41.5%; term/postterm: 44.7%; P = .02).

CONCLUSIONS:

Over half of preterm infants were undervaccinated at 19 months; one-third failed to catch up by 36 months. Strategies to improve vaccination of these high-risk infants are needed.

Advancing the Agenda in Pediatric Mental Health Education

BACKGROUND AND OBJECTIVES:

There is an urgent need to advance mental health (MH) education and/or training in pediatric residency programs, yet no consensus on how to achieve this. We created an operational framework from ideas provided by a diverse group of stakeholders on how to advance MH education.

METHODS:

Concept-mapping methodology was used, which involves brainstorming ideas by completing a focus prompt, sorting ideas into groups, and rating them for importance and feasibility. Multidimensional scaling and hierarchical cluster analysis grouped ideas into clusters. Average importance and feasibility were calculated for each statement and cluster and compared statistically in each cluster and between subgroups.

RESULTS:

Ninety-nine ideas were generated. Sorted ideas yielded a 7-cluster concept map: (1) modalities for MH training, (2) prioritization of MH, (3) systems-based practice, (4) self-awareness and/or relationship building, (5) training in clinical assessment of patients, (6) training in treatment, and (7) diagnosis-specific skills. Two hundred and sixteen participants rated ideas for importance and 209 for feasibility. Four clusters had a statistically significant difference between their importance and feasibility ratings (P < .001). Suburban and rural area respondents (versus urban) rated clusters higher in importance and feasibility (P < .004), trainees rated all clusters higher in feasibility than practicing clinicians, and MH professionals rated prioritization of MH higher in feasibility (3.42 vs 2.98; P < .001).

CONCLUSIONS:

This comprehensive set of ideas, especially those rated highly in both importance and feasibility, should inform curricular and policy initiatives. Differences between importance and feasibility may explain why there has been little progress in this field.

A Treatment-Decision Score for HIV-Infected Children With Suspected Tuberculosis

BACKGROUND:

Diagnosis of tuberculosis should be improved in children infected with HIV to reduce mortality. We developed prediction scores to guide antituberculosis treatment decision in HIV-infected children with suspected tuberculosis.

METHODS:

HIV-infected children with suspected tuberculosis enrolled in Burkina Faso, Cambodia, Cameroon, and Vietnam (ANRS 12229 PAANTHER 01 Study), underwent clinical assessment, chest radiography, Quantiferon Gold In-Tube (QFT), abdominal ultrasonography, and sample collection for microbiology, including Xpert MTB/RIF (Xpert). We developed 4 tuberculosis diagnostic models using logistic regression: (1) all predictors included, (2) QFT excluded, (3) ultrasonography excluded, and (4) QFT and ultrasonography excluded. We internally validated the models using resampling. We built a score on the basis of the model with the best area under the receiver operating characteristic curve and parsimony.

RESULTS:

A total of 438 children were enrolled in the study; 251 (57.3%) had tuberculosis, including 55 (12.6%) with culture- or Xpert-confirmed tuberculosis. The final 4 models included Xpert, fever lasting >2 weeks, unremitting cough, hemoptysis and weight loss in the past 4 weeks, contact with a patient with smear-positive tuberculosis, tachycardia, miliary tuberculosis, alveolar opacities, and lymph nodes on the chest radiograph, together with abdominal lymph nodes on the ultrasound and QFT results. The areas under the receiver operating characteristic curves were 0.866, 0.861, 0.850, and 0.846, for models 1, 2, 3, and 4, respectively. The score developed on model 2 had a sensitivity of 88.6% and a specificity of 61.2% for a tuberculosis diagnosis.

CONCLUSIONS:

Our score had a good diagnostic performance. Used in an algorithm, it should enable prompt treatment decision in children with suspected tuberculosis and a high mortality risk, thus contributing to significant public health benefits.

Reducing Variability in the Infant Sepsis Evaluation (REVISE): A National Quality Initiative

BACKGROUND:

Substantial variability exists in the care of febrile, well-appearing infants. We aimed to assess the impact of a national quality initiative on appropriate hospitalization and length of stay (LOS) in this population.

METHODS:

The initiative, entitled Reducing Variability in the Infant Sepsis Evaluation (REVISE), was designed to standardize care for well-appearing infants ages 7 to 60 days evaluated for fever without an obvious source. Twelve months of baseline and 12 months of implementation data were collected from emergency departments and inpatient units. Ill-appearing infants and those with comorbid conditions were excluded. Participating sites received change tools, run charts, a mobile application, live webinars, coaching, and a LISTSERV. Analyses were performed via statistical process control charts and interrupted time series regression. The 2 outcome measures were the percentage of hospitalized infants who were evaluated and hospitalized appropriately and the percentage of hospitalized infants who were discharged with an appropriate LOS.

RESULTS:

In total, 124 hospitals from 38 states provided data on 20 570 infants. The median site improvement in percentages of infants who were evaluated and hospitalized appropriately and in those with appropriate LOS was 5.3% (interquartile range = –2.5% to 13.7%) and 15.5% (interquartile range = 2.9 to 31.3), respectively. Special cause variation toward the target was identified for both measures. There was no change in delayed treatment or missed bacterial infections (slope difference 0.1; 95% confidence interval, –8.3 to 9.1).

CONCLUSIONS:

Reducing Variability in the Infant Sepsis Evaluation noted improvement in key aspects of febrile infant management. Similar projects may be used to improve care in other clinical conditions.

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