Urine biomarkers of acute kidney injury and association with brain MRI abnormalities in neonatal hypoxic-ischemic encephalopathy.

OBJECTIVE: Determine whether urine biomarkers NGAL (neutrophil gelatinase-associated lipocalin), KIM-1 (kidney injury molecule 1) and IL-18 (interleukin-18) are associated with abnormal MRI findings in neonates with hypoxic-ischemic encephalopathy (HIE) who underwent therapeutic hypothermia (TH). STUDY DESIGN: Secondary analysis of a multicenter, prospective study of neonates with HIE requiring TH. Urine biomarkers were obtained at 12 and 24 h of life (HOL). Brain MRI was scored per NICHD criteria. Association between biomarkers and MRI stage was determined. RESULTS: In 57 neonates with HIE, only IL-18 at 24 HOL was significantly increased in neonates with MRI Stage 2B or greater, compared to Stage 2A or less (mean 398.7 vs. 182.9 pg/mL, p = 0.024.) A multivariate model including IL-18 at 24 HOL and 5-min Apgar performed best, with an AUC of 0.84 (SE = 0.07, p = 0.02). CONCLUSIONS: Elevated urine IL-18 at 24 HOL was associated with more severe brain MRI abnormalities among neonates with HIE.

Provision and availability of genomic medicine services in Level IV neonatal intensive care units.

PURPOSE: To describe variation in genomic medicine services across level IV neonatal intensive care units (NICUs) in the United States and Canada. METHODS: We developed and distributed a novel survey to the 43 level IV NICUs belonging to the Children's Hospitals Neonatal Consortium, requesting a single response per site from a clinician with knowledge of the provision of genomic medicine services. RESULTS: Overall response rate was 74% (32/43). Although chromosomal microarray and exome or genome sequencing (ES or GS) were universally available, access was restricted for 22% (7/32) and 81% (26/32) of centers, respectively. The most common restriction on ES or GS was requiring approval by a specialist (41%, 13/32). Rapid ES/GS was available in 69% of NICUs (22/32). Availability of same-day genetics consultative services was limited (41%, 13/32 sites), and pre- and post-test counseling practices varied widely. CONCLUSION: We observed large inter-center variation in genomic medicine services across level IV NICUs: most notably, access to rapid, comprehensive genetic testing in time frames relevant to critical care decision making was limited at many level IV Children's Hospitals Neonatal Consortium NICUs despite a significant burden of genetic disease. Further efforts are needed to improve access to neonatal genomic medicine services.

Renal oximetry for early acute kidney injury detection in neonates with hypoxic ischemic encephalopathy receiving therapeutic hypothermia.

BACKGROUND: Neonates with hypoxic ischemic encephalopathy (HIE) receiving therapeutic hypothermia are at high risk of acute kidney injury (AKI). METHODS: We performed a two-site prospective observational study from 2018 to 2019 to evaluate the utility of renal near-infrared spectroscopy (NIRS) in detecting AKI in 38 neonates with HIE receiving therapeutic hypothermia. AKI was defined by a delayed rate of serum creatinine decline (< 33% on day 3 of life, < 40% on day 5, and < 46% on day 7). Renal saturation (Rsat) and systemic oxygen saturation (SpO2) were continuously measured for the first 96 h of life (HOL). Renal fractional tissue oxygen extraction (RFTOE) was calculated as (SpO2 - Rsat)/(SpO2). Using renal NIRS, urine biomarkers, and perinatal factors, logistic regression was performed to develop a model that predicted AKI. RESULTS: AKI occurred in 20 of 38 neonates (53%). During the first 96 HOL, Rsat was higher, and RFTOE was lower in the AKI group vs. the no AKI group (P < 0.001). Rsat > 70% had a fair predictive performance for AKI at 48-84 HOL (AUC 0.71-0.79). RFTOE ≤ 25 had a good predictive performance for AKI at 42-66 HOL (AUC 0.8-0.83). The final statistical model with the best fit to predict AKI (AUC = 0.88) included RFTOE at 48 HOL (P = 0.012) and pH of the infants' first postnatal blood gas (P = 0.025). CONCLUSIONS: Lower RFTOE on renal NIRS and pH on infant first blood gas may be early predictors for AKI in neonates with HIE receiving therapeutic hypothermia. A higher resolution version of the Graphical abstract is available as Supplementary information.

Associations of Stylet Use during Neonatal Intubation with Intubation Success, Adverse Events, and Severe Desaturation: A Report from NEAR4NEOS.

INTRODUCTION: Intubations are frequently performed procedures in neonatal intensive care units (NICU) and delivery rooms (DR). Unsuccessful first attempts are common as are tracheal intubation-associated events (TIAEs) and severe desaturations. Stylets are often used during intubation, but their association with intubation outcomes is unclear. OBJECTIVE: To compare intubation success, rate of relevant TIAEs, and severe desaturations in neonates intubated with and without stylets. METHODS: Tracheal intubations of neonates in the NICU or DR from 16 centers between October 2014 and December 2018, performed by neonatology or pediatric providers, were collected from the NEAR4NEOs international registry. Primary oral intubations with a laryngoscope were included in the analysis. First-attempt success, the occurrence of relevant TIAEs, and severe oxygen desaturation (≥20% saturation drop from baseline) were compared between intubations performed with versus without a stylet. Logistic regression with generalized estimate equations was used to control for covariates and clustering by sites. RESULTS: Out of 5,292 primary oral intubations, 3,877 (73%) utilized stylets. Stylet use varied considerably across the centers with a range between 0.5 and 100%. Stylet use was not associated with first-attempt intubation success, esophageal intubation, mainstem intubation, or severe desaturations after controlling for confounders. Patient size was associated with these outcomes and much more predictive of success. CONCLUSIONS: Stylet use during neonatal intubation was not associated with higher first-attempt intubation success, fewer relevant TIAEs, or less severe desaturations. These data suggest that stylets can be used based on individual preference, but stylet use may not be associated with better intubation outcomes.

Alternative Birth Plans and Unintended Maternal and Neonatal Consequences: A Review of the Literature.

IMPORTANCE: Birth plans are an important part of childbirth preparation for many women. OBJECTIVE: The aim of this review was to discuss some common requests, specifically home birth, water birth, placentophagy, lotus birth, vaccination refusal, and vaginal seeding, including evidence-based recommendations, perceived benefits, and potential maternal and neonatal consequences. EVIDENCE ACQUISITION: A literature search for each topic was undertaken using PubMed and Web of Science. For the home birth section, the MeSH terms home AND birth OR childbirth AND outcomes OR complications OR recommendations OR guidelines were used. For the vaccination section, birth OR childbirth OR maternal AND vaccination refusal were searched. For the remainder of the sections, umbilical cord AND nonseverance OR placentophagy OR vaginal seeding OR lotus birth were searched. A total of 523 articles were identified. The abstracts were reviewed by 2 authors (J.R.W. and J.A.R.); 60 of these articles were selected and used for this review. RESULTS: Home birth is currently not recommended in the United States. Immersion in water for labor is acceptable, but delivery should not occur in water. Placentophagy and lotus birth should be discouraged because of risk of neonatal infection. Vaccines should be administered in accordance with national guidelines. Vaginal seeding should be discouraged until more is known about the practice. CONCLUSIONS AND RELEVANCE: These evidence-based recommendations provide clear guidance for physicians so that the birthing experience can be enhanced for both mother and neonate without compromising safety. RELEVANCE STATEMENT: This is an evidence-based literature review of alternative birth plans and recommendations for directive counseling.

Genetic ancestry and its association with asthma exacerbations among African American subjects with asthma.

BACKGROUND: There are large and persisting disparities in severe asthma exacerbations by race-ethnicity, and African American subjects are among those at greatest risk. It is unclear whether this increased risk solely represents differences in environmental exposures and health care or whether there is a predisposing genetic component. OBJECTIVE: We sought to assess the relationship between genetic ancestry and severe exacerbations among African American subjects with asthma. METHODS: Participants were part of the Study of Asthma Phenotypes and Pharmacogenomic Interactions by Race-ethnicity (SAPPHIRE). These subjects were 12 to 56 years of age, received care from a single large health system, and had a physician's diagnosis of asthma. Genetic ancestry was estimated by using a set of validated ancestry informative markers. Severe exacerbations (ie, asthma-related emergency department visits, hospitalizations, and burst oral steroid use) were prospectively identified from health care claims. RESULTS: We assessed genetic ancestry in 392 African American subjects with asthma. The average proportion of African ancestry was 76.1%. A significant interaction was identified between ancestry and sex on severe exacerbations, such that the risk was significantly higher with increasing African ancestry among male but not female subjects. The association among male subjects persisted after adjusting for potential confounders (relative rate, 4.30 for every 20% increase in African ancestry; P = .029). CONCLUSIONS: African ancestry was significantly and positively associated with severe exacerbations among male African American subjects. These findings suggest that a portion of the risk of asthma exacerbations in this high-risk group is attributable to a genetic risk factor that partitions with ancestry.