A 4-week-old male neonate with a history of intermittent hypothermia in the newborn nursery presented with an acute onset of bilateral lower extremity paralysis and areflexia. Extensive workup demonstrated eosinophilic encephalomyelitis and multifocal hemorrhages of the brain and spinal cord. Funduscopic examination revealed bilateral chorioretinitis with macular scarring. The laboratory values were notable for peripheral eosinophilia and cerebrospinal fluid eosinophilic pleocytosis (28 white blood cells/µL, 28% eosinophils), markedly elevated protein (1214 mg/dL), and hypoglycorrhachia (20 mg/dL). Toxoplasma gondii immunoglobulin M (IgM) test result was positive. Reference testing obtained at the Palo Alto Medical Foundation Toxoplasma Serology Laboratory confirmed the diagnosis of congenital toxoplasmosis in the infant with a positive immunoglobulin G (IgG) dye test result, immunoglobulin A enzyme-linked immunosorbent assay, and IgM immunosorbent agglutination assay. The diagnosis of an infection acquired during gestation in the mother was established by a positive maternal IgG dye test result, IgM enzyme-linked immunosorbent assay, immunoglobulin A, immunoglobulin E, and low IgG avidity. At 6-month follow-up, the infant had marginal improvement in his retinal lesions and residual paraplegia with hyperreflexia and clonus of the lower extremities. A repeat MRI demonstrated interval development of encephalomalacia with suspected cortical laminar necrosis and spinal cord atrophy in the areas of previous hemorrhage. Clinicians should be aware of this severe spectrum of congenital toxoplasmosis disease and should remain vigilant for subtler signs that may prompt earlier testing, diagnosis, and treatment.
It remains uncertain whether treatment with adenotonsillectomy for obstructive sleep apnea in children improves cognitive function. The Preschool Obstructive Sleep Apnea Tonsillectomy and Adenoidectomy study was a prospective randomized controlled study in which researchers evaluated outcomes 12 months after adenotonsillectomy compared with no surgery in preschool children symptomatic for obstructive sleep apnea.METHODS:
A total of 190 children (age 3–5 years) were randomly assigned to early adenotonsillectomy (within 2 months) or to routine wait lists (12-month wait, no adenotonsillectomy [NoAT]). Baseline and 12-month assessments included cognitive and behavioral testing, medical assessment, polysomnography, and audiology. The primary outcome was global IQ at 12-month follow-up, measured by the Woodcock Johnson III Brief Intellectual Ability (BIA). Questionnaires included the Pediatric Sleep Questionnaire, Parent Rating Scale of the Behavioral Assessment System for Children–II, and Behavior Rating Inventory of Executive Function, Preschool Version.RESULTS:
A total of 141 children (75.8%) attended baseline and 12-month assessments, and BIA was obtained at baseline and 12-month follow-up for 61 and 60 participants in the adenotonsillectomy versus NoAT groups, respectively. No cognitive gain was found after adenotonsillectomy compared with NoAT, adjusted for baseline; BIA scores at 12-month follow-up were as follows: adenotonsillectomy, 465.46 (17.9) versus NoAT, 463.12 (16.6) (mean [SD]). Improvements were seen for polysomnogram arousals and apnea indices and for parent reports of symptoms (Pediatric Sleep Questionnaire), behavior (Behavior Assessment System for Children behavioral symptoms, P = .04), overall health, and daytime napping.CONCLUSIONS:
Structured testing showed no treatment-attributable improvement in cognitive functioning of preschool children 12 months after adenotonsillectomy compared with NoAT. Improvements were seen after adenotonsillectomy in sleep and behavior by using polysomnogram monitoring and parental questionnaires.
Phenotypic and biological characterization of rare monogenic disorders represents 1 of the most important avenues toward understanding the mechanisms of human disease. Among patients with SH3 and multiple ankyrin repeat domains 3 (SHANK3) mutations, a subset will manifest neurologic regression, psychosis, and mood disorders. However, which patients will be affected, when, and why are important unresolved questions. Authors of recent studies suggest neuronal SHANK3 expression is modulated by both inflammatory and hormonal stimuli. In this case series, we describe 4 independent clinical observations of an immunotherapy responsive phenotype of peripubertal-onset neuropsychiatric regression in 4 girls with pathogenic SHANK3 mutations. Each child exhibited a history of stable, mild-to-moderate lifelong developmental disability until 12 to 14 years of age, at which time each manifested a similar, subacute-onset neurobehavioral syndrome. Symptoms included mutism, hallucinations, insomnia, inconsolable crying, obsessive-compulsive behaviors, loss of self-care, and urinary retention and/or incontinence. Symptoms were relatively refractory to antipsychotic medication but improved after immunomodulatory treatment. All 4 patients exhibited chronic relapsing courses during a period of treatment and follow-up ranging from 3 to 6 years. Two of the 4 girls recovered their premorbid level of functioning. We briefly review the scientific literature to offer a conceptual and molecular framework for understanding these clinical observations. Future clinical and translational investigations in this realm may offer insights into mechanisms and therapies bridging immune function and human behavior.
The Management of Myelomeningocele Study (MOMS), a randomized trial of prenatal versus postnatal repair for myelomeningocele, found that prenatal surgery resulted in reduced hindbrain herniation and need for shunt diversion at 12 months of age and better motor function at 30 months. In this study, we compared adaptive behavior and other outcomes at school age (5.9–10.3 years) between prenatal versus postnatal surgery groups.METHODS:
Follow-up cohort study of 161 children enrolled in MOMS. Assessments included neuropsychological and physical evaluations. Children were evaluated at a MOMS center or at a home visit by trained blinded examiners.RESULTS:
The Vineland composite score was not different between surgery groups (89.0 ± 9.6 in the prenatal group versus 87.5 ± 12.0 in the postnatal group; P = .35). Children in the prenatal group walked without orthotics or assistive devices more often (29% vs 11%; P = .06), had higher mean percentage scores on the Functional Rehabilitation Evaluation of Sensori-Neurologic Outcomes (92 ± 9 vs 85 ± 18; P < .001), lower rates of hindbrain herniation (60% vs 87%; P < .001), had fewer shunts placed for hydrocephalus (49% vs 85%; P < .001) and, among those with shunts, fewer shunt revisions (47% vs 70%; P = .02) than those in the postnatal group. Parents of children repaired prenatally reported higher mean quality of life z scores (0.15 ± 0.67 vs 0.11 ± 0.73; P = .008) and lower mean family impact scores (32.5 ± 7.8 vs 37.0 ± 8.9; P = .002).CONCLUSIONS:
There was no significant difference between surgery groups in overall adaptive behavior. Long-term benefits of prenatal surgery included improved mobility and independent functioning and fewer surgeries for shunt placement and revision, with no strong evidence of improved cognitive functioning.
Interest in global health (GH) among pediatric residents continues to grow. GH opportunities in pediatric fellowship programs in the United States are poorly described. We aimed to evaluate GH offerings among accredited general and subspecialty pediatric fellowship programs and identify implementation barriers.METHODS:
This was a cross-sectional study by pediatric GH educators from the Association of Pediatric Program Directors Global Health Learning Community and the American Board of Pediatrics Global Health Task Force. Fellowship program directors and GH educators at accredited US pediatric fellowship programs were surveyed. Data were analyzed by using descriptive and comparative statistics.RESULTS:
Data were obtained from 473 of 819 (57.8%) fellowship programs, representing 111 institutions. Nearly half (47.4%) offered GH opportunities as GH electives only (44.2%) or GH tracks and/or fellowships (3.2%) (GHT/Fs). Pretravel preparation and supervision were variable. Programs offering GH opportunities, compared to those without, were more likely to report that GH training improves fellow education (81.9% vs 38.3%; P < .001) and recruitment (76.8% vs 35.9%; P < .001). Since 2005, 10 programs with GHT/Fs have graduated 46 fellows, most of whom are working in GH. Of those with GHT/Fs, 71% believe national accreditation of GH fellowships would define minimum programmatic standards; 64% believe it would improve recruitment and legitimize GH as a subspecialty.CONCLUSIONS:
GH experiences are prevalent in accredited US pediatric fellowship programs, and programs offering GH perceive that these opportunities improve fellow education and recruitment. Responses suggest that standards for GH opportunities during fellowship would be useful, particularly regarding pretravel preparation and mentorship for trainees.
Many transgender and gender-diverse people have a gender identity that does not conform to the binary categories of male or female; they have a nonbinary gender. Some nonbinary individuals are most comfortable with an androgynous gender expression. For those who have not yet fully progressed through puberty, puberty suppression with gonadotrophin-releasing hormone agonists can support an androgynous appearance. Although such treatment is shown to ameliorate the gender dysphoria and serious mental health issues commonly seen in transgender and gender-diverse young people, long-term use of puberty-suppressing medications carries physical health risks and raises various ethical dilemmas. In this Ethics Rounds, we analyze a case that raised issues about prolonged pubertal suppression for a patient with a nonbinary gender.
To describe the initial clinical response and care escalation needs for children with urinary tract infections (UTIs) resistant to third-generation cephalosporins while on discordant antibiotics.METHODS:
We performed a retrospective study of children <18 years old presenting to an acute care setting of 5 children’s hospitals and a large managed care organization from 2012 to 2017 with third-generation cephalosporin-resistant UTIs (defined as the growth of ≥50 000 colony-forming units per mL of Escherichia coli or Klebsiella spp. nonsusceptible to ceftriaxone with a positive urinalysis). We included children started on discordant antibiotics who had follow-up when culture susceptibilities resulted. Outcomes were escalation of care (emergency department visit, hospital admission, or ICU transfer while on discordant therapy) and clinical response at follow-up (classified as improved or not improved).RESULTS:
Of the 316 children included, 78% were girls and the median age was 2.4 years (interquartile range 0.6–6.5). Children were evaluated in the emergency department (56%) or clinic (43%), and 90% were started on a cephalosporin. A total of 7 of 316 children (2.2%; 95% confidence interval 0.8%–4.5%) experienced escalation of care. For the 230 children (73%) with clinical response recorded, 192 of 230 (83.5%; 95% confidence interval 78.0%–88.0%) experienced clinical improvement. In children with repeat urine testing while on discordant therapy, pyuria improved or resolved in 16 of 19 (84%) and urine cultures sterilized in 11 of 17 (65%).CONCLUSIONS:
Most children with third-generation cephalosporin-resistant UTIs started on discordant antibiotics experienced initial clinical improvement, and few required escalation of care. Our findings suggest that narrow-spectrum empiric therapy is appropriate while awaiting final urine culture results.
Gonadotropin-releasing hormone analogues are commonly prescribed to suppress endogenous puberty for transgender adolescents. There are limited data regarding the mental health benefits of this treatment. Our objective for this study was to examine associations between access to pubertal suppression during adolescence and adult mental health outcomes.METHODS:
Using a cross-sectional survey of 20 619 transgender adults aged 18 to 36 years, we examined self-reported history of pubertal suppression during adolescence. Using multivariable logistic regression, we examined associations between access to pubertal suppression and adult mental health outcomes, including multiple measures of suicidality.RESULTS:
Of the sample, 16.9% reported that they ever wanted pubertal suppression as part of their gender-related care. Their mean age was 23.4 years, and 45.2% were assigned male sex at birth. Of them, 2.5% received pubertal suppression. After adjustment for demographic variables and level of family support for gender identity, those who received treatment with pubertal suppression, when compared with those who wanted pubertal suppression but did not receive it, had lower odds of lifetime suicidal ideation (adjusted odds ratio = 0.3; 95% confidence interval = 0.2–0.6).CONCLUSIONS:
This is the first study in which associations between access to pubertal suppression and suicidality are examined. There is a significant inverse association between treatment with pubertal suppression during adolescence and lifetime suicidal ideation among transgender adults who ever wanted this treatment. These results align with past literature, suggesting that pubertal suppression for transgender adolescents who want this treatment is associated with favorable mental health outcomes.
Although simple febrile seizures are relatively common and benign in toddlers, it is important to rule out any underlying critical disease that necessitates further intervention and treatment. Thyroid storm, the extreme manifestation of hyperthyroidism, is relatively rare and not often considered in the differential diagnosis of a febrile seizure despite its high mortality rate. Here, we report 1 of the youngest patients with thyroid storm, who initially presented with a febrile seizure. After reevaluation, the 2-year-9-month-old patient was discovered to have thyromegaly, which led to recognition that her persistent tachycardia and widened pulse pressure were likely signs of thyrotoxicosis. Laboratory results were consistent with primary hyperthyroidism due to Graves’ disease. Thyroid storm was then diagnosed on the basis of clinical features including gastrointestinal and central nervous system disturbances. Treatment with methimazole, propranolol, hydrocortisone, and Lugol’s iodine solution was used. This medication regimen was safe and effective with restoration of a euthyroid state after 2 months and no recurrence of seizures. Improved awareness of hyperthyroidism and thyroid storm can lead to prompt diagnosis and treatment of this endocrine emergency, thus reducing mortality and morbidity. Pediatricians should consider this diagnosis in children with febrile seizures and suggestive vital signs and physical examination findings.
Clinicians are urged to optimize communication with families, generally without empirical practical recommendations. The objective of this study was to identify core behaviors associated with good communication during and after an unsuccessful resuscitation, including parental perspectives.METHODS:
Clinicians from different backgrounds participated in a standardized, videotaped, simulated neonatal resuscitation in the presence of parent actors. The infant remained pulseless; participants communicated with the parent actors before, during, and after discontinuing resuscitation. Twenty-one evaluators with varying expertise (including 6 bereaved parents) viewed the videos. They were asked to score clinician-parent communication and identify the top communicators. In open-ended questions, they were asked to describe 3 aspects that were well done and 3 that were not. Answers to open-ended questions were coded for easily reproducible behaviors. All the videos were then independently reviewed to evaluate whether these behaviors were present.RESULTS:
Thirty-one participants’ videos were examined by 21 evaluators (651 evaluations). Parents and actors agreed with clinicians 81% of the time about what constituted optimal communication. Good communicators were more likely to introduce themselves, use the infant's name, acknowledge parental presence, prepare the parents (for the resuscitation, then death), stop resuscitation without asking parents, clearly mention death, provide or enable proximity (clinician-parent, infant-parent, clinician-infant, mother-father), sit down, decrease guilt, permit silence, and have knowledge about procedures after death. Consistently, clinicians who displayed such behaviors had evaluations >9 out of 10 and were all ranked top 10 communicators.CONCLUSIONS:
During a neonatal end-of-life scenario, many simple behaviors, identified by parents and providers, can optimize clinician-parent communication.
Opioid-exposed infants frequently qualify for early intervention (EI). However, many eligible families choose not to enroll in this voluntary service. This study aims to understand the perceptions and experiences that may impact engagement with, and the potential benefits of, EI services among mothers in recovery from opioid use disorders (OUDs).METHODS:
We conducted semistructured qualitative interviews (n = 22) and 1 focus group (n = 6) with mothers in recovery from OUDs in western Massachusetts. Transcripts were coded and analyzed by using a descriptive approach.RESULTS:
The mean participant age was 32 years, and 13 had a high school degree or less. Five major themes emerged revealing mothers’ development through stages of engagement in EI services: (1) fear, guilt, and shame related to drug use (emotions acting as barriers to enrollment); (2) the question of whether it is "needed" (deciding whether there is value in EI for opioid-exposed infants); (3) starting with "judgment" (baseline level of perceived stigma that parents in recovery associate with EI); (4) breaking down the "wall" (how parents overcome the fear and perceived judgment to build partnerships with providers); and (5) "above and beyond" (need for a personal connection with mothers and concrete supports through EI in addition to the child-focused services provided).CONCLUSIONS:
Barriers to engagement in EI among mothers in recovery from OUDs include a range of emotions, perceived stigma, and ambivalence. An effort to purposefully listen to and care for mothers through a strengths-based, bigenerational approach may help establish greater connections and foster stronger EI engagement among families affected by OUDs.
Material hardship has been associated with adverse health care use patterns for children with special health care needs (CSHCN). In this study, we assessed if resilience factors were associated with lower emergency department (ED) visits and unmet health care needs and if they buffered associations between material hardship and health care use for CSHCN and children without special health care needs.METHODS:
A cross-sectional study using the 2016 National Survey of Children’s Health, restricted to low-income participants (<200% federal poverty level). Separately, for CSHCN and children without special health care needs, weighted logistic regression was used to measure associations between material hardship, 2 resilience factors (family resilience and neighborhood cohesion), and 2 measures of use. Moderation was assessed using interaction terms. Mediation was assessed using structural equation models.RESULTS:
The sample consisted of 11 543 children (weighted: n = 28 465 581); 26% were CSHCN. Material hardship was associated with higher odds of ED visits and unmet health care needs for all children. Resilience factors were associated with lower odds of unmet health care needs for CSHCN (family resilience adjusted odds ratio: 0.58; 95% confidence interval: 0.36–0.94; neighborhood cohesion adjusted odds ratio: 0.53; 95% confidence interval: 0.32–0.88). For CSHCN, lower material hardship mediated associations between resilience factors and unmet health care needs. Neighborhood cohesion moderated the association between material hardship and ED visits (interaction term: P = .02).CONCLUSIONS:
Among low-income CSHCN, resilience factors may buffer the effects of material hardship on health care use. Future research should evaluate how resilience factors can be incorporated into programs to support CSHCN.
Children born extremely preterm (EP) (<26 weeks’ gestation) have lower cognitive scores and an increased rate of cognitive impairment compared with their term-born peers. However, the neuropsychological presentation of these EP individuals in adulthood has not been described. The aim of this study was to examine neuropsychological outcomes in early adulthood after EP birth in the 1995 EPICure cohort and to investigate if the rate of intellectual impairment changed longitudinally.METHODS:
A total of 127 young adults born EP and 64 term-born controls had a neuropsychological assessment at 19 years of age examining general cognitive abilities (IQ), visuomotor abilities, prospective memory, and aspects of executive functions and language.RESULTS:
Adults born EP scored significantly lower than term-born controls across all neuropsychological tests with effect sizes (Cohen’s d) of 0.7 to 1.2. Sixty percent of adults born EP had impairment in at least 1 neuropsychological domain; deficits in general cognitive functioning and visuomotor abilities were most frequent. The proportion of EP participants with an intellectual impairment (IQ <70) increased by 6.7% between 11 and 19 years of age (P = .02). Visuospatial functioning in childhood predicted visuomotor functioning at 19 years.CONCLUSIONS:
Adults born EP continue to perform lower than their term-born peers in general cognitive abilities as well as across a range of neuropsychological functions, indicating that these young adults do not show improvement overtime. The prevalence of intellectual impairment increased from 11 years into adulthood.
The Pediatric Transition Experience Measure (P-TEM) is an 8-item, parent-reported measure that globally assesses hospital-to-home transition quality from discharge through follow-up. Our goal was to examine the convergent validity of the P-TEM with existing, validated process and outcome measures of pediatric hospital-to-home transitions.METHODS:
This was a prospective, cohort study of English-speaking parents and legal guardians who completed the P-TEM after their children’s discharge from a tertiary children’s hospital between January 2016 and October 2016. By using data from 3 surveys, we assessed convergent validity by examining associations between total and domain-specific P-TEM scores (0–100 scale) and 4 pediatric hospital-to-home transition validation measures: (1) Child Hospital Consumer Assessment of Healthcare Providers and Systems Discharge Composite, (2) Center of Excellence on Quality of Care Measures for Children With Complex Needs parent-reported transition measures, (3) change in health-related quality of life from admission to postdischarge, and (4) 30-day emergency department revisits or readmissions.RESULTS:
P-TEM total scores were 7.5 points (95% confidence interval: 4.6 to 10.4) higher for participants with top-box responses on the Child Hospital Consumer Assessment of Healthcare Providers and Systems Discharge Composite compared with those of participants with lower Discharge Composite scores. Participants with highet P-TEM scores (ie, top-box responses) had 6.3-points–greater improvement (95% confidence interval: 2.8 to 9.8) in health-related quality of life compared with participants who reported lower P-TEM scores. P-TEM scores were not significantly associated with 7- or 30-day reuse.CONCLUSIONS:
The P-TEM demonstrated convergent validity with existing hospital-to-home process and outcome validation measures in a population of hospitalized children.
Children frequently receive low-value services that do not improve health, but it is unknown whether the receipt of these services differs between publicly and privately insured children.METHODS:
We analyzed 2013–2014 Medicaid Analytic eXtract and IBM MarketScan Commercial Claims and Encounters databases. Using 20 measures of low-value care (6 diagnostic testing measures, 5 imaging measures, and 9 prescription drug measures), we compared the proportion of publicly and privately insured children in 12 states who received low-value services at least once or twice in 2014; the proportion of publicly and privately insured children who received low-value diagnostic tests, imaging tests, and prescription drugs at least once; and the proportion of publicly and privately insured children eligible for each measure who received the service at least once.RESULTS:
Among 6 951 556 publicly insured children and 1 647 946 privately insured children, respectively, 11.0% and 8.9% received low-value services at least once, 3.9% and 2.8% received low-value services at least twice, 3.2% and 3.8% received low-value diagnostic tests at least once, 0.4% and 0.4% received low-value imaging tests at least once, and 8.4% and 5.5% received low-value prescription drug services at least once. Differences in the proportion of eligible children receiving each service were typically small (median difference among 20 measures, public minus private: +0.3 percentage points).CONCLUSIONS:
In 2014, 1 in 9 publicly insured and 1 in 11 privately insured children received low-value services. Differences between populations were modest overall, suggesting that wasteful care is not highly associated with payer type. Efforts to reduce this care should target all populations regardless of payer mix.
Much remains unknown about the consequences of very low birth weight (VLBW) and bronchopulmonary dysplasia (BPD) on adult lungs. We hypothesized that VLBW adults would have impaired lung function compared with controls, and those with a history of BPD would have worse lung function than those without.METHODS:
At age 26 to 30 years, 226 VLBW survivors of the New Zealand VLBW cohort and 100 term controls born in 1986 underwent lung function tests including spirometry, plethysmographic lung volumes, diffusing capacity of the lung for carbon monoxide, and single-breath nitrogen washout (SBN2).RESULTS:
An obstructive spirometry pattern was identified in 35% VLBW subjects versus 14% controls, with the majority showing mild obstruction. Compared with controls, VLBW survivors demonstrated significantly lower forced expiratory volume in 1 second (FEV1), FEV1/forced vital capacity (FVC) ratio (FEV1/FVC), forced expiratory flow at 25% to 75% of FVC and higher residual volume (RV), RV/total lung capacity (TLC) ratio (RV/TLC), decreased diffusing capacity of the lung for carbon monoxide, and increased phase III slope for SBN2. The differences persisted after adjustment for sex and smoking status. Within the VLBW group, subjects with BPD showed significant reduction in FEV1, FEV1/FVC, and forced expiratory flow at 25% to 75% of FVC, and increase in RV, RV/TLC, and phase III slope for SBN2, versus subjects without. The differences remained after adjustment for confounders.CONCLUSIONS:
Adult VLBW survivors showed a higher incidence of airflow obstruction, gas trapping, reduced gas exchange, and increased ventilatory inhomogeneity versus controls. The findings suggest pulmonary effects due to VLBW persist into adulthood, and BPD is a further insult on small airway function.
To assess the association between gentamicin exposure in the neonatal period and hearing in school age.METHODS:
This study included children exposed to a high-dose (6 mg/kg) gentamicin regimen as neonates (2004–2012), invited for follow-up at school age, and a healthy age-matched control group. We assessed hearing with pure tone audiometry including the extended high-frequency (EHF) range. Outcomes were average hearing thresholds in the midfrequencies (0.5–4 kHz) and the EHFs (9–16 kHz). The measures of gentamicin exposure were cumulative dose and highest trough plasma concentration. We used linear regression models to assess the impact of gentamicin exposure, and other peri- and postnatal morbidities, on hearing thresholds.RESULTS:
A total of 219 gentamicin-exposed and 33 healthy-control children were included in the audiological analysis. In the gentamicin cohort, 39 (17%) had a birth weight <1500 g. Median cumulative doses and trough plasma concentrations were 30 (interquartile range 24–42) mg/kg and 1.0 (interquartile range 0.7–1.2) mg/L, respectively. Median hearing thresholds for the midfrequencies and the EHFs were 2.5 (0 to 6.3) dB hearing level and –1.7 (–5.0 to 5.0) dB hearing level, both of which were within the normal range. In an adjusted analysis, increasing hearing thresholds were associated with lower birth weight and postnatal middle-ear disease but not level of gentamicin exposure. After adjusting for birth weight, there was no difference in hearing threshold between the gentamicin-exposed cohort and healthy controls.CONCLUSIONS:
Exposure to a high-dose gentamicin regimen in the neonatal period was not associated with an increase in hearing thresholds in schoolchildren being able to complete audiometry.