Congenital adrenal calcifications as the first clinical indication of sphingosine lyase insufficiency syndrome: A case report and review of the literature.

Sphingosine Lyase Insufficiency Syndrome (SPLIS) or SGPL1 Deficiency is a newly described entity that is characterized by steroid-resistant nephrotic syndrome, primary adrenal insufficiency, lymphopenia, ichthyosis, and/or endocrine and neurologic abnormalities. The earliest identification of SGPL1 pathogenic variants in association with this syndrome was reported in 2017. Since then, at least 36 patients have been reported with this pediatric syndrome. Here, we report a new patient with SPLIS who had a prenatal finding of adrenal calcifications, congenital nephrotic syndrome, and abnormal newborn screening concerning for Severe Combined Immunodeficiency. We conclude that SPLIS is a clinically recognizable condition with prenatal onset. This case should increase awareness of SPLIS in the differential diagnosis for adrenal calcifications. We present a case on the severe end of the clinical spectrum of SPLIS, and a review of the literature.

Supportive care utilization and treatment toxicity in children with Down syndrome and acute lymphoid leukaemia at free-standing paediatric hospitals in the United States.

Although inferior outcomes of children with Down syndrome (DS) and acute lymphoid leukaemia (ALL) are established, national supportive care patterns for these patients are unknown. A validated retrospective cohort of paediatric patients diagnosed with ALL from 1999 to 2011 was assembled from the US Pediatric Health Information System (PHIS) database to examine organ toxicity, sepsis, and resource utilization in children with and without DS. Among 10699 ALL patients, 298 had DS-ALL (2·8%). In a multivariate model, DS was associated with increased risk of cardiovascular (odds ratio [OR] 2·0, 95% confidence interval [CI] 1·6-2·7), respiratory (OR 2·1, 95% CI: 1·6-2·9), neurologic (OR 3·4, 95% CI 1·9-6·2), and hepatic (OR 1·4, 95% CI 1·0-1·9) dysfunction and sepsis (OR 1·8, 95% CI: 1·4-2·4). Children with DS-ALL used significantly more respiratory support, insulin, and anti-infectives, including broad-spectrum Gram-positive agents, quinolones, and azoles. They used significantly fewer analgesics and antiemetics compared to non-DS-ALL children. Ultimately, this study confirms the increased risk of infectious and end-organ toxicity in children with DS-ALL and quantifies important differences in resource utilization between children with DS and non-DS ALL. These findings highlight the importance of investigating the impact of these care variations and developing specific supportive care guidelines for this population.

Transfer Patterns Among Infants Born at 28 to 34 Weeks' Gestation.

BACKGROUND: Although postnatal transfer patterns among high-risk (eg, extremely preterm or surgical) infants have been described, transfer patterns among lower-risk populations are unknown. The objective was to examine transfer frequency, indication, timing, and trajectory among very and moderate preterm infants. METHODS: Observational study of the US Vermont Oxford Network all NICU admissions database from 2016 to 2021 of inborn infants 280/7 to 346/7 weeks. Infants' first transfer was assessed by gestational age, age at transfer, reason for transfer, and transfer trajectory. RESULTS: Across 467 hospitals, 294 229 infants were eligible, of whom 12 552 (4.3%) had an initial disposition of transfer. The proportion of infants transferred decreased with increasing gestational age (9.6% [n = 1415] at 28 weeks vs 2.4% [n = 2646] at 34 weeks) as did the median age at time of transfer (47 days [interquartile range 30-73] at 28 weeks vs 8 days [interquartile range 3-16] at 34 weeks). The median post menstrual age at transfer was 34 or 35 weeks across all gestational ages. The most common reason for transfer was growth or discharge planning (45.0%) followed by medical and diagnostic services (30.2%), though this varied by gestation. In this cohort, 42.7% of transfers were to a higher-level unit, 10.2% to a same-level unit, and 46.7% to a lower-level unit, with indication reflecting access to specific services. CONCLUSIONS: Over 4% of very and moderate preterm infants are transferred. In this population, the median age of transfer is later and does not reflect immediate care needs after birth, but rather the provision of risk-appropriate care.

The impact of volume and neonatal level of care on outcomes of moderate and late preterm infants.

OBJECTIVE: Evaluate the relationship of neonatal unit level of care (LOC) and volume with mortality or morbidity in moderate-late preterm (MLP) (32-36 weeks' gestation) infants. DESIGN: Retrospective cohort study of 650,865 inborn MLP infants in 4976 hospitals-years using 2003-2015 linked administrative data from 4 states. Exposure was combined neonatal LOC and MLP annual volume. The primary outcome was death or morbidity (respiratory distress syndrome, severe intraventricular hemorrhage, necrotizing enterocolitis, sepsis, infection, pneumothorax, extreme length of stay) with components as secondary outcomes. Poisson regression models adjusted for patient characteristics with a random effect for unit were used. RESULTS: In adjusted models, high-volume level 2 units had a lower risk of the primary outcome compared to low-volume level 3 units (aIRR 0.90 [95% CI 0.83-0.98] vs. aIRR 1.13 [95% CI 1.03-1.24], p < 0.001) CONCLUSION: MLP infants had improved outcomes in high-volume level 2 units compared to low-volume level 3 units in adjusted analysis.

Preterm Birth Risk and Maternal Nativity, Ethnicity, and Race.

Importance: Immigrant birthing people have lower rates of preterm birth compared with their US-born counterparts. This advantage and associated racial and ethnic disparities across the gestational age spectrum have not been examined nationally. Objective: To examine associations of maternal nativity, ethnicity, and race with preterm birth. Design, Setting, and Participants: This cohort study used birth certificates from the National Vital Statistics System to analyze in-hospital liveborn singleton births in the US between January 1, 2009, and December 31, 2018. Data were analyzed from January to June 2023. Exposure: Mutually exclusive nativity, ethnicity, and race subgroups were constructed using nativity (defined as US-born or non-US-born), ethnicity (defined as Hispanic or non-Hispanic), and race (defined as American Indian or Alaska Native, Asian, Black, Native Hawaiian or Other Pacific Islander, White, or other [individuals who selected other race or more than 1 race]). Main Outcomes and Measures: The primary outcome of interest was preterm birth. Modified Poisson and multinomial logistic regression models quantified relative risk (RR) of preterm birth overall (<37 weeks' gestation) and by gestational category (late preterm: 34-36 weeks' gestation; moderately preterm: 29-33 weeks' gestation; and extremely preterm: <29 weeks' gestation) for each maternal nativity, ethnicity, and race subgroup compared with the largest group, US-born non-Hispanic White (hereafter, White) birthing people. The RR of preterm birth overall and by category was also measured within each racial and ethnic group by nativity. Models were adjusted for maternal demographic and medical covariates, birth year, and birth state. Results: A total of 34 468 901 singleton live births of birthing people were analyzed, with a mean (SD) age at delivery of 28 (6) years. All nativity, ethnicity, and race subgroups had an increased adjusted risk of preterm birth compared with US-born White birthing people except for non-US-born White (adjusted RR, 0.85; 95% CI, 0.84-0.86) and Hispanic (adjusted RR, 0.98; 95% CI, 0.97-0.98) birthing people. All racially and ethnically minoritized groups had increased adjusted risks of extremely preterm birth compared with US-born White birthing people. Non-US-born individuals had a decreased risk of preterm birth within each subgroup except non-Hispanic Native Hawaiian or Other Pacific Islander individuals, in which immigrants had significantly increased risk of overall (adjusted RR, 1.07; 95% CI, 1.01-1.14), moderately (adjusted RR, 1.10; 95% CI, 0.92-1.30), and late (adjusted RR, 1.11; 95% CI, 1.02-1.22) preterm birth than their US-born counterparts. Conclusions and Relevance: Results of this cohort study suggest heterogeneity of preterm birth across maternal nativity, ethnicity, and race and gestational age categories. Understanding these patterns could aid the design of targeted preterm birth interventions and policies, especially for birthing people typically underrepresented in research.

Association Between Neonatal Intensive Care Unit Type and Quality of Care in Moderate and Late Preterm Infants.

Importance: A higher level of care improves outcomes in extremely and very preterm infants, yet the impact of neonatal intensive care unit (NICU) level on moderate and late preterm (MLP) care quality is unknown. Objective: To examine the association between NICU type and care quality in MLP (30-36 weeks' gestation) and extremely and very preterm (25-29 weeks' gestation) infants. Design, Setting, and Participants: This cohort study was a prospective analysis of 433 814 premature infants born in 465 US hospitals between January 1, 2016, and December 31, 2020, without anomalies and who survived more than 12 hours and were transferred no more than once. Data were from the Vermont Oxford Network all NICU admissions database. Exposures: NICU types were defined as units with ventilation restrictions without surgery (type A with restrictions, similar to American Academy of Pediatrics [AAP] level 2 NICUs), without surgery (type A) and with surgery not requiring cardiac bypass (type B, similar to AAP level 3 NICUs), and with all surgery (type C, similar to AAP level 4 NICUs). Main Outcomes and Measures: The primary outcome was gestational age (GA)-specific composite quality measures using Baby-Measure of Neonatal Intensive Care Outcomes Research (Baby-MONITOR) for extremely and very preterm infants and an adapted MLP quality measure for MLP infants. Secondary outcomes were individual component measures of each scale. Composite scores were standardized observed minus expected scores, adjusted for patient characteristics, averaged, and expressed with a mean of 0 and SD of 1. Between May 2021 and October 2022, Kruskal-Wallis tests were used to compare scores by NICU type. Results: Among the 376 219 MLP (204 181 [54.3%] male, 172 038 [45.7%] female; mean [SD] GA, 34.2 [1.7] weeks) and 57 595 extremely and very preterm (30 173 [52.4%] male, 27 422 [47.6%] female; mean [SD] GA, 27.7 [1.4] weeks) infants included, 6.6% received care in type A NICUs with restrictions, 29.3% in type A NICUs without restrictions, 39.7% in type B NICUs, and 24.4% in type C NICUs. The MLP infants had lower MLP-QM scores in type C NICUs (median [IQR]: type A with restrictions, 0.4 [-0.1 to 0.8]; type A, 0.4 [-0.4 to 0.9]; type B, 0.1 [-0.7 to 0.7]; type C, -0.7 [-1.6 to 0.4]; P < .001). No significant differences were found in extremely and very preterm Baby-MONITOR scores by NICU type. In type C NICUs, MLP infants had lower scores in no extreme length of stay and change-in-weight z score. Conclusions and Relevance: In this cohort study, composite quality scores were lower for MLP infants in type C NICUs, whereas extremely and very preterm composite quality scores were similar across NICU types. Policies facilitating care for MLP infants at NICUs with less complex subspecialty services may improve care quality delivered to this prevalent, at-risk population.

County-Level Maternal Vulnerability and Preterm Birth in the US.

Importance: Appreciation for the effects of neighborhood conditions and community factors on perinatal health is increasing. However, community-level indices specific to maternal health and associations with preterm birth (PTB) have not been assessed. Objective: To examine the association of the Maternal Vulnerability Index (MVI), a novel county-level index designed to quantify maternal vulnerability to adverse health outcomes, with PTB. Design, Setting, and Participants: This retrospective cohort study used US Vital Statistics data from January 1 to December 31, 2018. Participants included 3 659 099 singleton births at 22 plus 0/7 to 44 plus 6/7 weeks of gestation born in the US. Analyses were conducted from December 1, 2021, through March 31, 2023. Exposure: The MVI, a composite measure of 43 area-level indicators, categorized into 6 themes reflecting physical, social, and health care landscapes. Overall MVI and theme were stratified by quintile (very low to very high) by maternal county of residence. Main Outcomes and Measures: The primary outcome was PTB (gestational age <37 weeks). Secondary outcomes were PTB categories: extreme (gestational age ≤28 weeks), very (gestational age 29-31 weeks), moderate (gestational age 32-33 weeks), and late (gestational age 34-36 weeks). Multivariable logistic regression quantified associations of MVI, overall and by theme, with PTB, overall and by PTB category. Results: Among 3 659 099 births, 298 847 (8.2%) were preterm (male, 51.1%; female, 48.9%). Maternal race and ethnicity included 0.8% American Indian or Alaska Native, 6.8% Asian or Pacific Islander, 23.6% Hispanic, 14.5% non-Hispanic Black, 52.1% non-Hispanic White, and 2.2% with more than 1 race. Compared with full-term births, MVI was higher for PTBs across all themes. Very high MVI was associated with increased PTB in unadjusted (odds ratio [OR], 1.50 [95% CI, 1.45-1.56]) and adjusted (OR, 1.07 [95% CI, 1.01-1.13]) analyses. In adjusted analyses of PTB categories, MVI had the largest association with extreme PTB (adjusted OR, 1.18 [95% CI, 1.07-1.29]). Higher MVI in the themes of physical health, mental health and substance abuse, and general health care remained associated with PTB overall in adjusted models. While the physical health and socioeconomic determinant themes were associated with extreme PTB, physical health, mental health and substance abuse, and general health care themes were associated with late PTB. Conclusions and Relevance: The findings of this cohort study suggest that MVI was associated with PTB even after adjustment for individual-level confounders. The MVI is a useful measure for county-level PTB risk that may have policy implications for counties working to lower preterm rates and improve perinatal outcomes.

Measuring quality of care in moderate and late preterm infants.

OBJECTIVE: To examine quality measures for moderate and late preterm (MLP) infants. STUDY DESIGN: By prospectively analyzing Vermont Oxford Network's all NICU admissions database, we adapted Baby-MONITOR, a composite quality measure for extremely/very preterm infants, for MLP infants. We examined correlations between the adapted MLP quality measure (MLP-QM) in MLP infants and Baby-MONITOR in extremely and very preterm infants. RESULT: We studied 376,219 MLP (30-36 weeks GA) and 57,595 extremely/very preterm (25-29 weeks GA) infants from 465 U.S. hospitals born from 2016 to 2020. MLP-QM summary scores in MLP infants had weak correlation with Baby-MONITOR scores in extremely and very preterm infants (r = 0.47). There was weak correlation among survival (r = 0.19), no pneumothorax (r = 0.35), and no infection after 3 days (r = 0.45), but strong correlation among human milk at discharge (r = 0.79) and no hypothermia (r = 0.76). CONCLUSION: Modest correlation among hospital care measures in two preterm populations suggests the need for MLP-specific care measures.

Variation and Temporal Trends in Delivery Room Management of Moderate and Late Preterm Infants.

BACKGROUND: Although delivery room (DR) intervention decreases with increasing gestational age (GA), little is known about DR management of moderate and late preterm (MLP) infants. METHODS: Using the Vermont Oxford Network database of all NICU admissions, we examined the receipt of DR interventions including supplemental oxygen, positive pressure ventilation, continuous positive airway pressure, endotracheal tube ventilation, chest compressions, epinephrine, and surfactant among MLP infants (30 to 36 weeks') without congenital anomalies born from 2011 to 2020. Pneumothorax was examined as a potential resuscitation-associated complication. Intervention frequency was assessed at the infant- and hospital-level, stratified by GA and over time. RESULTS: Overall, 55.3% of 616 110 infants (median GA: 34 weeks) from 483 Vermont Oxford Network centers received any DR intervention. Any DR intervention frequency decreased from 89.7% at 30 weeks to 44.2% at 36 weeks. From 2011 to 2020, there was an increase in the provision of continuous positive airway pressure (17.9% to 47.8%, P ≤.001) and positive pressure ventilation (22.9% to 24.9%, P ≤.001) and a decrease in endotracheal tube ventilation (6.9% to 4.0% P ≤.001), surfactant administration (3.5% to 1.3%, P ≤.001), and pneumothorax (1.9% to 1.6%, P ≤.001). Hospital rates of any DR intervention varied (median 54%, interquartile range 47% to 62%), though the frequency was similar across hospitals with different NICU capabilities after adjustment. CONCLUSIONS: The DR management of MLP infants varies at the individual- and hospital-level and is changing over time. These findings illustrate the differing interpretation of resuscitation guidelines and emphasize the need to study MLP infants to improve evidence-based DR care.

Mixed Phenotype Acute Leukemia with Low Hypodiploidy in a Pediatric Patient.

We describe the case of a 16 year-old female with mixed phenotype acute leukemia B/myeloid, NOS (formerly biphenotypic leukemia) with masked hypodiploidy and somatic TP53 and CDKN2A/B deletions. She achieved morphologic remission with lymphoid-directed multi-agent chemotherapy, but experienced an early medullary relapse 11 months from initial diagnosis. Her case details the unusual finding of hypodiploidy in a patient with ambiguous lineage leukemia and highlights the complexity of therapy selection for these high-risk patients.