The Landscape of Resource Utilization After Resuscitation of 22-, 23-, and 24-Weeks' Gestation Infants.

OBJECTIVE: To compare estimated healthcare resources needed to care for 22 through 24 weeks' gestation infants. STUDY DESIGN: This multicenter, retrospective cohort study included 1505 live in-born and out-born infants 22 through 24 weeks' gestational age at delivery from 6 pediatric tertiary care hospitals from 2011 through 2020. Median neonatal intensive care unit (NICU) length of stay (LOS) for each gestational age was used as a proxy for hospital resource utilization, and the number of comorbidities and medical technology use for each infant were used as estimates of future medical care needs. Data were analyzed using Kruskal-Wallis with Nemenyi's posthoc test and Fisher's exact test. RESULTS: Of the identified newborns, 22-week infants had shorter median LOS than their 23- and 24-week counterparts due to low survival rates. There was no significant difference in LOS for surviving 22-week infants compared with surviving 23-week infants. Surviving 22-week infants had similar proportions of comorbidities and medical technology use as 23-week infants. CONCLUSIONS: Compared with 23- and 24-week infants, 22-week infants did not use a disproportionate amount of hospital resources. Twenty-two-week infants should not be excluded from resuscitation based on concern for increased hospital care and medical technology requirements. As overall resuscitation efforts and survival rates increase for 22-week infants, future research will be needed to assess the evolution of these results.

Physician Perceptions on Quality of Life and Resuscitation Preferences for Extremely Early Newborns.

OBJECTIVE: The study aimed to explore physician views on whether extremely early newborns will have an acceptable quality of life (QOL), and if these views are associated with physician resuscitation preferences. STUDY DESIGN: We performed a cross-sectional survey of neonatologists and maternal fetal medicine (MFM) attendings, fellows, and residents at four U.S. medical centers exploring physician views on future QOL of extremely early newborns and physician resuscitation preferences. Mixed-effects logistic regression models examined association of perceived QOL and resuscitation preferences when adjusting for specialty, level of training, gender, and experience with ex-premature infants. RESULTS: A total of 254 of 544 (47%) physicians were responded. A minority of physicians had interacted with surviving extremely early newborns when they were ≥3 years old (23% of physicians in pediatrics/neonatology and 6% in obstetrics/MFM). The majority of physicians did not believe an extremely early newborn would have an acceptable QOL at the earliest gestational ages (11% at 22 and 23% at 23 weeks). The majority of physicians (73%) believed that having an extremely preterm infant would have negative effects on the family's QOL. Mixed-effects logistic regression models (odds ratio [OR], 95% confidence interval [CI]) revealed that physicians who believed infants would have an acceptable QOL were less likely to offer comfort care only at 22 (OR: 0.19, 95% CI: 0.05-0.65, p < 0.01) and 23 weeks (OR: 0.24, 95% CI: 0.07-0.78, p < 0.02). They were also more likely to offer active treatment only at 24 weeks (OR: 9.66, 95% CI: 2.56-38.87, p < 0.01) and 25 weeks (OR: 19.51, 95% CI: 3.33-126.72, p < 0.01). CONCLUSION: Physician views of extremely early newborns' future QOL correlated with self-reported resuscitation preferences. Residents and obstetric physicians reported more pessimistic views on QOL. KEY POINTS: · Views of QOL varied by specialty and level of training.. · Contact with former extremely early newborns was limited.. · QOL views were associated with preferred resuscitation practices..

Patterns of Urinary Neutrophil Gelatinase-Associated Lipocalin and Acute Kidney Injury in Neonates Receiving Cardiopulmonary Bypass.

Elevated urinary neutrophil gelatinase-associated lipocalin (uNGAL) predicts acute kidney injury (AKI) in children following cardiopulmonary bypass (CPB) during cardiac surgery, but little is known about uNGAL's predictive ability in neonates in this setting. We sought to determine the relationship between AKI and post-CPB uNGAL in neonates in the first 72 post-operative hours. METHODS: Urine samples for uNGAL analysis were collected at preoperative baseline and serially post-operatively from 76 neonates undergoing CPB. Mixed-effects regression models and logistic models assessed associations between uNGAL and AKI (controlling for sex, gestational age, CPB time, surgical complexity, and age at surgery). Receiver-operator curves were applied to define optimal uNGAL cut-off values for AKI diagnosis. RESULTS: Between 0 and 4 h post-operatively, uNGAL values did not differ between neonates with and without AKI. After 4 h until 16 h post-operatively, significant time-wise separation occurred between uNGAL values of neonates with AKI and those without AKI. Odds ratios at each time point significantly exceeded unity, peaking at 10 h post-operatively (3.48 (1.58, 8.71)). Between 4 and 16 h post-operatively, uNGAL discriminated AKI from no-AKI, with a sensitivity of 0.63 (0.49, 0.75) and a specificity of 0.68 (0.62, 0.74) at a cut-off value of 100 ng/mL. CONCLUSION: After 4 h until 16 h post-operatively, elevated uNGAL is associated with AKI in neonates receiving CPB during cardiac surgery; however, this relationship is more complex than in older children.

In vivo positron emission tomography imaging with [¹¹C]ABP688: binding variability and specificity for the metabotropic glutamate receptor subtype 5 in baboons.

PURPOSE: Metabotropic glutamate receptor subtype 5 (mGluR5) dysfunction has been implicated in several disorders. [(11)C]ABP688, a positron emission tomography (PET) ligand targeting mGluR5, could be a valuable tool in the development of novel therapeutics for these disorders by establishing in vivo drug occupancy. Due to safety concerns in humans, these studies may be performed in nonhuman primates. Therefore, in vivo characterization of [(11)C]ABP688 in nonhuman primates is essential. METHODS: Test-retest studies were performed in baboons (Papio anubis) to compare modeling approaches and determine the optimal reference region. The mGluR5-specific antagonist 3-((2-methyl-1,3-thiazol-4-yl)ethynyl)pyridine (MTEP) was then used in test-block studies, in which ligand binding was measured before and after MTEP administration. Test/block data were analyzed both by calculating changes in binding and using a graphical approach, which allowed estimation of both MTEP occupancy and nonspecific binding. RESULTS: Test-retest results, which have not been previously reported for [(11)C]ABP688, indicated that [(11)C]ABP688 variability is low using an unconstrained two-tissue compartment model. The most appropriate, though not ideal, reference region was found to be the gray matter of the cerebellum. Using these optimal modeling techniques on the test/block data, about 90% occupancy was estimated by the graphical approach. CONCLUSION: These studies are the first to demonstrate the specificity of [(11)C]ABP688 for mGluR5 with in vivo PET in nonhuman primates. The results indicate that, in baboons, occupancy of mGluR5 is detectable by in vivo PET, a useful finding for proceeding to human studies, or performing further baboon studies, quantifying the in vivo occupancy of novel therapeutics targeting mGluR5.

Elevated serotonin 1A binding in remitted major depressive disorder: evidence for a trait biological abnormality.

Several biological abnormalities in major depressive disorder (MDD) persist during episode remission, including altered serotonin neurotransmission, and may reflect underlying pathophysiology. We previously described elevated brain serotonin 1A (5-HT(1A)) receptor binding in antidepressant-naive (AN) subjects with MDD within a major depressive episode (MDE) compared with that in healthy controls using positron emission tomography (PET). In this study, we measured 5-HT(1A) receptor binding in unmedicated subjects with MDD during sustained remission, hypothesizing higher binding compared with that in healthy controls, and binding comparable with currently depressed AN subjects, indicative of a biological trait. We compared 5-HT(1A) binding potential (BP(F)) assessed through PET scanning with [(11)C]WAY-100635 in 15 subjects with recurrent MDD in remission for >or=12 months and off antidepressant medication for >or=6 months, 51 healthy controls, and 13 AN MDD subjects in a current MDE. Metabolite-corrected arterial input functions were acquired for the estimation of BP(F). Remitted depressed subjects had higher 5-HT(1A) BP(F) compared with healthy controls; this group difference did not vary significantly in magnitude across brain regions. 5-HT(1A) BP(F) was comparable in remitted and currently depressed subjects. Elevated 5-HT(1A) BP(F) level among subjects with remitted MDD appears to be a trait abnormality in MDD, which may underlie recurrent MDEs. Future studies should evaluate the role of genetic and environmental factors in producing elevated 5-HT(1A) BP(F) and MDD, and should examine whether 5-HT(1A) BP(F) is a vulnerability factor to MDEs that could have a role in screening high-risk populations for MDD.