Quantile contours and allometric modelling for risk classification of abnormal ratios with an application to asymmetric growth-restriction in preterm infants

We develop an approach to risk classification based on quantile contours and allometric modelling of multivariate anthropometric measurements. We propose the definition of allometric direction tangent to the directional quantile envelope, which divides ratios of measurements into half-spaces. This in turn provides an operational definition of directional quantile that can be used as cutoff for risk assessment. We show the application of the proposed approach using a large dataset from the Vermont Oxford Network containing observations of birthweight (BW) and head circumference (HC) for more than 150,000 preterm infants. Our analysis suggests that disproportionately growth-restricted infants with a larger HC-to-BW ratio are at increased mortality risk as compared to proportionately growth-restricted infants. The role of maternal hypertension is also investigated.Comment: 31 pages, 3 figures, 8 table

Trends in resources for neonatal intensive care at delivery hospitals for infants born younger than 30 weeks' gestation, 2009-2020

Importance: In an ideal regionalized system, all infants born very preterm would be delivered at a large tertiary hospital capable of providing all necessary care. Objective: To examine whether the distribution of extremely preterm births changed between 2009 and 2020 based on neonatal intensive care resources at the delivery hospital. Design, setting, and participants: This retrospective cohort study was conducted at 822 Vermont Oxford Network (VON) centers in the US between 2009 and 2020. Participants included infants born at 22 to 29 weeks' gestation, delivered at or transferred to centers participating in the VON. Data were analyzed from February to December 2022. Exposures: Hospital of birth at 22 to 29 weeks' gestation. Main outcomes and measures: Birthplace neonatal intensive care unit (NICU) level was classified as A, restriction on assisted ventilation or no surgery; B, major surgery; or C, cardiac surgery requiring bypass. Level B centers were further divided into low-volume (<50 inborn infants at 22 to 29 weeks' gestation per year) and high-volume (≥50 inborn infants at 22 to 29 weeks' gestation per year) centers. High-volume level B and level C centers were combined, resulting in 3 distinct NICU categories: level A, low-volume B, and high-volume B and C NICUs. The main outcome was the change in the percentage of births at hospitals with level A, low-volume B, and high-volume B or C NICUs overall and by US Census region. Results: A total of 357 181 infants (mean [SD] gestational age, 26.4 [2.1] weeks; 188 761 [52.9%] male) were included in the analysis. Across regions, the Pacific (20 239 births [38.3%]) had the lowest while the South Atlantic (48 348 births [62.7%]) had the highest percentage of births at a hospital with a high-volume B- or C-level NICU. Births at hospitals with A-level NICUs increased by 5.6% (95% CI, 4.3% to 7.0%), and births at low-volume B-level NICUs increased by 3.6% (95% CI, 2.1% to 5.0%), while births at hospitals with high-volume B- or C-level NICUs decreased by 9.2% (95% CI, -10.3% to -8.1%). By 2020, less than half of the births for infants at 22 to 29 weeks' gestation occurred at hospitals with high-volume B- or C-level NICUs. Most US Census regions followed the nationwide trends; for example, births at hospitals with high-volume B- or C-level NICUs decreased by 10.9% [95% CI, -14.0% to -7.8%) in the East North Central region and by 21.1% (95% CI, -24.0% to -18.2%) in the West South Central region. Conclusions and relevance: This retrospective cohort study identified concerning deregionalization trends in birthplace hospital level of care for infants born at 22 to 29 weeks' gestation. These findings should serve to encourage policy makers to identify and enforce strategies to ensure that infants at the highest risk of adverse outcomes are born at the hospitals where they have the best chances to attain optimal outcomes

The Vermont oxford neonatal encephalopathy registry: Rationale, methods, and initial results

BACKGROUND: In 2006, the Vermont Oxford Network (VON) established the Neonatal Encephalopathy Registry (NER) to characterize infants born with neonatal encephalopathy, describe evaluations and medical treatments, monitor hypothermic therapy (HT) dissemination, define clinical research questions, and identify opportunities for improved care. METHODS: Eligible infants were ≥ 36 weeks with seizures, altered consciousness (stupor, coma) during the first 72 hours of life, a 5 minute Apgar score of ≤ 3, or receiving HT. Infants with central nervous system birth defects were excluded. RESULTS: From 2006–2010, 95 centers registered 4232 infants. Of those, 59% suffered a seizure, 50% had a 5 minute Apgar score of ≤ 3, 38% received HT, and 18% had stupor/coma documented on neurologic exam. Some infants experienced more than one eligibility criterion. Only 53% had a cord gas obtained and only 63% had a blood gas obtained within 24 hours of birth, important components for determining HT eligibility. Sixty-four percent received ventilator support, 65% received anticonvulsants, 66% had a head MRI, 23% had a cranial CT, 67% had a full channel encephalogram (EEG) and 33% amplitude integrated EEG. Of all infants, 87% survived. CONCLUSIONS: The VON NER describes the heterogeneous population of infants with NE, the subset that received HT, their patterns of care, and outcomes. The optimal routine care of infants with neonatal encephalopathy is unknown. The registry method is well suited to identify opportunities for improvement in the care of infants affected by NE and study interventions such as HT as they are implemented in clinical practice

Discharge Age and Weight for Very Preterm Infants in Six Countries: 2012-2020

BACKGROUND Postmenstrual age for surviving infants without congenital anomalies born at 24-29 weeks' gestational age from 2005 to 2018 in the USA increased 8 days, discharge weight increased 316 grams, and median discharge weight z-score increased 0.19 standard units. We asked whether increases were observed in other countries. METHODS We evaluated postmenstrual age, weight, and weight z-score at discharge of surviving infants without congenital anomalies born at 24-29 weeks' gestational age admitted to Vermont Oxford Network member hospitals in Austria, Ireland, Italy, Switzerland, the UK, and the USA from 2012 to 2020. RESULTS After adjustment, the median postmenstrual age at discharge increased significantly in Austria (3.6 days, 99% CI [1.0, 6.3]), Italy (4.0 days [2.3, 5.6]), and the USA (5.4 days [5.0, 5.8]). Median discharge weight increased significantly in Austria (181 grams, 99% CI [95, 267]), Ireland (234 [143, 325]), Italy (133 [83, 182]), and the USA (207 [194, 220]). Median discharge weight z-score increased in Ireland (0.24 standard units, 99% CI [0.12, 0.36]) and the USA (0.15 [0.13, 0.16]). Discharge on human milk increased in Italy, Switzerland, and the UK, while going home on cardiorespiratory monitors decreased in Austria, Ireland, and USA and going home on oxygen decreased in Ireland. CONCLUSIONS In this international cohort of neonatal intensive care units, postmenstrual discharge age and weight increased in some, but not all, countries. Processes of care at discharge did not change in conjunction with age and weight increases

Discharge age and weight for very preterm infants in six countries: 2012-2020

Postmenstrual age for surviving infants without congenital anomalies born at 24-29 weeks' gestational age from 2005 to 2018 in the USA increased 8 days, discharge weight increased 316 grams, and median discharge weight z-score increased 0.19 standard units. We asked whether increases were observed in other countries. We evaluated postmenstrual age, weight, and weight z-score at discharge of surviving infants without congenital anomalies born at 24-29 weeks' gestational age admitted to Vermont Oxford Network member hospitals in Austria, Ireland, Italy, Switzerland, the UK, and the USA from 2012 to 2020. After adjustment, the median postmenstrual age at discharge increased significantly in Austria (3.6 days, 99% CI [1.0, 6.3]), Italy (4.0 days [2.3, 5.6]), and the USA (5.4 days [5.0, 5.8]). Median discharge weight increased significantly in Austria (181 grams, 99% CI [95, 267]), Ireland (234 [143, 325]), Italy (133 [83, 182]), and the USA (207 [194, 220]). Median discharge weight z-score increased in Ireland (0.24 standard units, 99% CI [0.12, 0.36]) and the USA (0.15 [0.13, 0.16]). Discharge on human milk increased in Italy, Switzerland, and the UK, while going home on cardiorespiratory monitors decreased in Austria, Ireland, and USA and going home on oxygen decreased in Ireland. In this international cohort of neonatal intensive care units, postmenstrual discharge age and weight increased in some, but not all, countries. Processes of care at discharge did not change in conjunction with age and weight increases

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe