Journal of Pediatrics最新文献

Objective: To assess how medical complexity and neighborhood opportunity jointly affect cognitive, motor, and language Bayley's Scales of Infant Development. Secondary objectives involved identifying the factors contributing to developmental disparities across diverse racial and ethnic groups.

Study design: Electronic health records from a Southern California high-risk infant follow-up clinic were analyzed for 440 infants from 2014 through 2023 who had either had neonatal intensive care unit stays, prematurity, very low birthweight, or developmental delay risk. Medical complexity was categorized using the Pediatric Medical Complexity Algorithm (PMCA) into complex chronic (CC), noncomplex chronic (NCC), or non-chronic (NC). Neighborhood opportunity was assessed using the Child Opportunity Index 2.0 (COI). Developmental progress was tracked from ages 4 to 35.6 months.

Results: Of the cohort, 56% were male, and 67% were born prematurely, with 143 NC, 115 NCC, and 182 CC cases. Developmental scores showed a progressive decline with increased medical complexity. CC infants had lower cognitive (β= -15.20, p<0.001, 95% CI: -18.75, -11.7), motor (β= -20.50, p<0.001, 95% CI: -24.25, -16.8), and language scores (β=-11.88, p<0.001, 95% CI = -15.13 to -8.6) compared with NC infants. Lower COI was linked with decreased language scores (β= -0.07, p = 0.005, 95% CI: 0.01, 0.12) but not cognitive or motor scores.

Conclusions: In high-risk infants, the adverse effects of medical complexities on developmental outcomes exceeded those of prematurity and additionally varied according to child neighborhood opportunity.

Objective: To determine if chorioamnionitis is associated with an increased risk of adverse 2-year outcomes among infants with hypoxic-ischemic encephalopathy (HIE).

Study design: This cohort study included all infants with moderate to severe HIE treated with therapeutic hypothermia and enrolled on the High-dose Erythropoietin for Asphyxia and Encephalopathy Trial. Clinical chorioamnionitis (CC) was defined as a diagnosis made by a treating obstetrician and histologic chorioamnionitis (HC) was defined as placental inflammation observed on histology. We used proportional odds regression to determine the associations between CC, HC, and an ordinal 2-year neurodevelopmental outcome measure: no neurodevelopmental impairment (NDI), mild NDI, moderate NDI, severe NDI, or death.

Results: Of 500 infants, 65 (13%) were exposed to CC. Of 317 infants with placental data available, 125 (39%) were exposed to HC. Infants exposed to CC (odds ratio 0.57, 95% CI 0.34-0.95) and those exposed to HC (odds ratio 0.62, 95% CI 0.40-0.96) had a lower severity of primary outcome than unexposed infants. Infants exposed to chorioamnionitis also had lower frequencies of sentinel events (CC: P = .001; HC: P = .005), central pattern magnetic resonance imaging brain injury (CC: P = .02; HC: P = .02), and electroencephalogram background abnormalities (CC: P = .046; HC: P = .02), compared with unexposed infants.

Conclusions: Infants with HIE who were exposed to chorioamnionitis had lower severity of 2-year outcomes than unexposed infants. Our findings suggest that chorioamnionitis may lead to a lower severity of brain dysfunction than other pathophysiologic mechanisms of encephalopathy.

Objective: To determine if number of neonatal morbidities is associated with death or severe neurodevelopmental impairment (sNDI) among infants born extremely preterm who survived to 36 weeks' postmenstrual age (PMA).

Study design: This is a retrospective cohort analysis of prospectively collected data from 15 NICHD Neonatal Research Network centers. Neonatal morbidities and 2-year outcomes were examined for 3794 infants born at 22 to 26 weeks' gestation from 2014 through 2019 who survived to 36 weeks' PMA.

Results: Serious brain injury (SBI), bronchopulmonary dysplasia (BPD), and severe retinopathy of prematurity (ROP) had the strongest bivariate associations with death or sNDI (ORs, 95% CI): 3.96 (3.39, 4.64), 3.41 (2.94, 3.95), and 2.66 (2.28, 3.11)], respectively. A morbidity count variable was constructed using these morbidities. The estimated ORs and 95% CI for death or sNDI with any 1, any 2, or all 3 of these morbidities, adjusted for maternal and infant characteristics and hospital of birth, increased from 2.75 (2.25, 3.37) to 6.10 (4.83, 7.70) to 12.90 (9.07, 18.36), respectively. Corresponding rates of late death or sNDI with none, any 1, any 2, and all 3 morbidities were 12.6%, 30.3%, 51.9%, and 69.9%, respectively. The estimated logistic model produced predictions of death or sNDI with moderate discrimination (C-statistic [95% CI]: 0.765 [0.749, 0.782]) and good calibration (Intercept [CITL] = -0.004, slope = 1.026).

Conclusions: Among infants born extremely preterm who survived to 36 weeks' PMA, a count of SBI, BPD, and severe ROP predicts death or sNDI.

Trial registration: ClinicalTrials.gov ID Generic Database: NCT00063063.

Objective: To determine whether inhaled nitric oxide (iNO) treatment of early pulmonary hypertension (PH) would decrease the risk of death or bronchopulmonary dysplasia (BPD) among infants born extremely preterm.

Study design: This was a single-center, masked, randomized controlled trial involving infants born at ≤29 weeks' gestation and requiring positive pressure ventilation. Exclusion criteria included infants of COVID-19 positive mothers, large patent ductus arteriosus with left to right shunting, left ventricle dysfunction (ejection fraction <40%), significant congenital anomalies/genetic disorders, or iNO treatment by clinicians prior to the study echocardiogram. Initial echocardiogram was performed at 72 ± 24 hours of life to randomize infants with early PH into 2 study arms (iNO vs placebo). Serial echocardiograms were performed every 24-48 hours, up to 14 days of life. Treatment was weaned until PH resolved (responders) or if no improvement was documented ≥72-hours (nonresponders). Primary outcome was death or BPD at 36-weeks postmenstrual age.

Results: From July 2019 to October 2023, 683 eligible infants were admitted. We excluded 88 infants; 413 mothers declined consent or were not approached. iNO treatment was clinically started for 51 infants due to hypoxic respiratory failure. Screening echocardiograms were completed for 180 infants; of these, 32 infants with early PH were randomized to iNO or placebo groups. After a planned interim analysis, termination of the trial was recommended by the Data Safety Monitoring Committee because of futility.

Conclusion: iNO treatment does not reduce the risk of BPD or death among extremely preterm infants with echocardiographic evidence of early pulmonary hypertension without hypoxic respiratory failure.

Objective: To determine whether management guidelines for infants born extremely preterm are representative for those infants <25 weeks of gestation.

Study design: Three guidelines were reviewed: the 2022 European Consensus Guidelines on the Management of Respiratory Distress Syndrome, the 2017 American Academy of Pediatrics Guidelines for Perinatal Care, and the 2020/2021 International Liaison Committee on Resuscitation guidelines. All referenced studies for overlapping recommendations were reviewed. Data extracted included the total number and proportion of infants <25 weeks of gestation in the original articles referred in the guidelines. Where the exact number of infants <25 weeks of gestation was unobtainable, this was conservatively estimated by statistical deduction.

Results: Eight recommendations were included in 2 or more guidelines: (1) antenatal corticosteroids, (2) antenatal magnesium sulfate, (3) delayed cord clamping, (4) thermoregulation at birth, (5) initial oxygen concentration at birth, (6) continuous positive airway pressure, (7) surfactant, and (8) parenteral nutrition. In total, 519 studies (n = 409 986) informed these 8 recommendations, of which 335 (64.5%) were randomized controlled trials (n = 78 325). Across all studies, an estimated 59 360 (14.5%) infants were <25 weeks of gestation. Within randomized controlled trials alone, an estimated 5873 (7.5%) infants were <25 weeks of gestation. A total of 196 (37.8%) studies did not include any infants <25 weeks of gestation.

Conclusions: Infants born <25 weeks of gestation are not well-represented in the evidence used to develop major clinical guidelines for infants born extremely preterm. Future studies should provide evidence for this population as a distinct cohort.

Objective: To investigate the initial and long-term clinical course of periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome after tonsillectomy regarding fever episodes and nonfebrile PFAPA-related symptoms.

Study design: An observational cohort study with retrospective and cross-sectional data based on 86 of 101 patients who underwent tonsillectomy for PFAPA between January 2006 and March 2020 from a cohort of 336 patients diagnosed with PFAPA as children. Data were collected by structured telephone interviews and review of medical records. Parents were interviewed regarding initial response to tonsillectomy and the clinical course following tonsillectomy. Patients, if ≥18 years old, or parents, if patients were younger, were interviewed regarding symptoms present at the time of this long-term follow-up study.

Results: Six months after tonsillectomy, 45 of 86 participants (54%) had no symptoms of PFAPA, 19 (22%) had only nonfebrile PFAPA-related symptoms, 17 (20%) had ongoing but fewer or milder fever episodes, 1 (1%) had ongoing febrile episodes without improvement, and 4 (5%) had missing data because parents were unavailable. In 10 of 45 patients with initial remission, fever episodes reappeared 0.5-4.5 years after tonsillectomy. At long-term follow-up (median 8.8 years [range 2.8-16.1 years] after tonsillectomy), 54 of 86 (63%) had no symptoms of PFAPA, 15 (17%) had febrile episodes, generally with longer intervals between flares than before tonsillectomy, and 17 (20%) had nonfebrile PFAPA-related symptoms.

Conclusions: While PFAPA symptoms resolve or are milder post-tonsillectomy among most of the patients, the long-term outcomes showing residual symptoms among a substantial minority should be considered when evaluating tonsillectomy as a treatment option for PFAPA. Increased awareness of persistent symptoms after tonsillectomy may improve understanding and health care for these patients.

Objective: To characterize clinical, hemodynamic, imaging, and pathologic findings in children with pulmonary arterial hypertension (PAH) and variants in SRY-box transcription factor 17 (SOX17), a novel risk gene linked to heritable and congenital heart disease-associated PAH.

Study design: We assembled a multi-institutional cohort of children with PAH and SOX17 variants enrolled in the Pediatric Pulmonary Hypertension Network (PPHNet) and other registries. Subjects were identified through exome and PAH gene panel sequencing. Data were collected from registries and retrospective chart review.

Results: We identified 13 children (8 female, 5 male) aged 1.6-16 years at diagnosis with SOX17 variants and PAH. Seven patients had atrial septal defects and 2 had patent ductus arteriosus. At diagnostic cardiac catheterization, patients had severely elevated mean pulmonary artery (PA) pressure (mean 78, range 47-124 mmHg) and markedly elevated indexed pulmonary vascular resistance (mean 25.9, range 4.9-55 WU∗m²). No patients responded to acute vasodilator testing. Catheter and computed tomography angiography imaging demonstrated atypical PA anatomy including severely dilated main pulmonary arteries, lack of tapering in third and fourth order pulmonary arteries, tortuous 'corkscrewing' pulmonary arteries, and abnormal capillary 'blush.' Several children had PA stenoses and 2 had systemic arterial abnormalities. Histologic examination of explanted lungs from 3 patients disclosed plexiform arteriopathy and extensive aneurysmal dilation of alveolar septal capillaries.

Conclusions: SOX17-associated PAH is a distinctive genetic syndrome characterized by early onset severe PAH, extensive pulmonary vascular abnormalities, and high prevalence of congenital heart disease with intracardiac and interarterial shunts, suggesting a role for SOX17 in pulmonary vascular development.

Objective: To elucidate how the clinical presentation of Pediatric Inflammatory Multisystem Syndrome temporally associated with Severe Acute Respiratory Syndrome-related Coronavirus 2 (PIMS-TS) was influenced by the successive variants of concern (VOC) and patient age.

Study design: A nationwide PIMS-TS registry was established in Germany in May 2020, shortly after the first cases were described in the US and United Kingdom. The registry captured information on patient characteristics, clinical course, laboratory findings, imaging, and outcome. All pediatric hospitals in Germany, along with one in Austria, were invited to participate. Between March 18, 2020, and April 30, 2023, 920 cases were reported.

Results: By examining a combination of data on clinical features, laboratory findings, treatment, imaging results, and outcomes, our analysis demonstrated disease severity to have continuously declined over the course of the Wildtype, Alpha, Delta, and Omicron waves. Based on clinical symptoms, laboratory and diagnostic findings, and intensive care unit admission rates, older children, irrespective of the related VOC, were shown to experience more severe, acute PIMS-TS; however, they had lower rates of coronary aneurysm.

Conclusions: During the course of COVID-19 pandemic, as each new VOC emerged, PIMS-TS lessened in severity. In parallel, older children came to experience more debilitating disease.