Contributions of the NICHD neonatal research network's generic database to documenting and advancing the outcomes of extremely preterm infants

The Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network (NRN) maintains a database of extremely preterm infants known as the Generic Database (GDB). Begun in 1987, this database now includes more than 91,000 infants, most of whom are extremely preterm (<29 weeks gestation). The GDB has been the backbone of the NRN, providing high quality, prospectively collected data to study the changing epidemiology of extreme prematurity and its outcomes over time. In addition, GDB data have been used to generate hypotheses for prospective studies and to develop new clinical trials by providing information about the numbers and characteristics of available subjects and the expected event rates for conditions and complications to be studied. Since its inception, the GDB has been the basis of more than 200 publications in peer-reviewed journals, many of which have had a significant impact on the field of neonatology.     

Safety and immunogenicity of NVX-CoV2373 (TAK-019) vaccine in healthy Japanese adults: Interim report of a phase I/II randomized controlled trial

BackgroundWe evaluated the safety and immunogenicity of NVX-CoV2373, a recombinant SARS-CoV-2 nanoparticle vaccine, in healthy Japanese participants.MethodsThis phase 1/2, randomized, observer-blind, placebo-controlled trial conducted in Japan (two sites), enrolled healthy Japanese adults aged ≥ 20 years with no history/risk of SARS-CoV-2 infection and no prior exposure to other approved/investigational SARS-CoV-2 vaccines or treatments. Participants were stratified by age (< 65 or ≥ 65 years) and randomized to receive two doses of either NVX-CoV2373 (5 μg SARS-CoV-2 rS; 50 μg Matrix-M1) or placebo, 21 days apart. Primary outcomes were safety and immunogenicity assessed by serum IgG antibody levels against SARS-CoV-2 rS protein on day 36. Herein, we report the primary data analysis at 4 weeks after the second dose, ahead of 12-month follow-up completion (data cut-off: 8 May 2021).ResultsBetween 12 February 2021 and 17 March 2021, 326 subjects were screened, and 200 participants enrolled and randomized: NVX-CoV2373, n = 150; placebo, n = 50. Solicited adverse events (AEs) through 7 days after each injection occurred in 121/150 (80.7%) and 11/50 (22.0%) participants in the NVX-CoV2373 and placebo arms, respectively. In the NVX-CoV2373 arm, tenderness and injection site pain were the most frequently reported solicited AEs after each vaccination, irrespective of age. Robust immune responses occurred with NVX-CoV2373 (n = 150) by day 36: IgG geometric mean fold rise (95% confidence interval) 259 (219, 306); seroconversion rate 100% (97.6, 100). No such response occurred with placebo (n = 49).ConclusionTwo doses of NVX-CoV2373 given with a 21-day interval demonstrated acceptable safety and induced robust anti-SARS-CoV-2 immune responses in healthy Japanese adults. Funding: Takeda Pharmaceutical Company Limited and Japan Agency for Medical Research and Development (AMED). ClinicalTrials.gov identifier: NCT04712110.     

Key Social Determinants to Narrow the Gap between Health-adjusted Life Expectancy and Life Expectancy in Megacities

ObjectiveImprovement in the quality of life is reflected in the narrowing of the gap between health-adjusted life expectancy (HALE) and life expectancy (LE). The effect of megacity expansion on narrowing the gap is rarely reported. This study aimed to disclose this potential relationship.MethodsAnnual life tables were constructed from identified death records and population counts from multiple administrative sources in Guangzhou, China, from 2010 to 2020. Joinpoint regression was used to evaluate the temporal trend. Generalized principal component analysis and multilevel models were applied to examine the county-level association between the gap and social determinants.ResultsAlthough LE and HALE in megacities are increasing steadily, their gap is widening. Socio-economic and health services are guaranteed to narrow this gap. Increasing personal wealth, a growing number of newborns and healthy immigrants, high urbanization, and healthy aging have helped in narrowing this gap.ConclusionIn megacities, parallel LE and HALE growth should be highly considered to narrow their gap. Multiple social determinants need to be integrated as a whole to formulate public health plans.     

Time trend of exposure to the phthalate plasticizer substitute DINCH in Germany from 1999 to 2017: Biomonitoring data on young adults from the Environmental Specimen Bank (ESB)

DINCH (cyclohexane-1,2-dicarboxylic acid-diisononyl ester) is a phthalate plasticizer substitute introduced into the market in 2002. It is increasingly used especially in the production of toys, food contact materials and medical devices. In this measurement campaign on 24-h urine samples of young adults (20–29 years) from the German Environmental Specimen Bank (ESB) collected in 2010, 2011, 2013, 2015 and 2017 (in total 300 samples, 60 samples/year) we analyzed three specific, oxidized DINCH metabolites (OH-MINCH: cyclohexane-1,2-dicarboxylic acid-mono(hydroxy-isononyl) ester; cx-MINCH: cyclohexane-1,2-dicarboxylic acid-mono(carboxy-isooctyl) ester, oxo-MINCH: cyclohexane-1,2-dicarboxylic acid-mono(oxo-isononyl) ester). We merged these data with earlier data of the ESB from the years 1999–2012 and are now able to report levels and time trends of internal DINCH exposure from 1999 to 2017.After first detections of the major oxidized DINCH metabolite OH-MINCH in 2006 (6.7%) detection rates rapidly increased to 43.3% in 2009, 80% in 2010 and 98.3% in 2011 and 2012. From the year 2013 on we could detect OH-MINCH in every urine sample analyzed. The median concentrations of OH-MINCH rapidly increased from 0.15 μg/L in 2010 to twice the concentration in 2011 (0.31 μg/L) with further increases in 2013 (0.37 μg/L), 2015 (0.59 μg/L) and 2017 (0.70 μg/L). Similar increases, albeit at lower detection rates and concentration levels, could be observed for cx-MINCH and oxo-MINCH. All metabolites strongly correlate with each other.For the ESB study population, DINCH exposures are still far below health based guidance values such as the German Human Biomonitoring Value (HBM-I; 4,500 μg/L for the sum of OH-MINCH and cx-MINCH) or the tolerable daily intake (TDI) of EFSA (1 mg/kg bw/d). The median daily DINCH intake (DI) calculated for 2017 was 0.23 μg/kg bw/d, thus 4,310-times lower than the TDI. The maximum DI calculated for one individual in 2012 (42.60 μg/kg bw/d) was a factor of more than 20 below the TDI.The ongoing increase in DINCH exposure needs to be closely monitored in the future, including populations with potentially higher exposures such as children. This close monitoring will enable timely exposure and risk reduction measures if exposures reached critical levels, or if new toxicological data lead to lower health based guidance values. DINCH belongs to the European Human Biomonitoring Initiative (HBM4EU) priority substances for which policy relevant questions still have to be answered.     

Comparison of dynamic occlusal contacts during chewing between children with primary dentition and normal adult females

ObjectiveInvestigation of dynamic occlusal contacts when food particles are being pulverized during chewing is of interest for many researchers and clinicians. However, measurement of dynamic occlusal contacts during chewing is difficult, and differences between children and adults have not been established. The purpose of this study is to test the hypothesis that dynamic occlusal contacts of children differ from those of adult females.Subjectsand methods: Thirteen healthy children (4–6 years of age; mean age 5 years, 7 months) and thirteen adult females (18–26 years of age; mean age 20 years, 7 months) with normal occlusion participated in this study. Occlusal contact area (OCA) was estimated with a developed measurement system combining 3-D digitization of tooth shape with 3-D tracking of mandibular movements (1) during the closing stroke, (2) at the maximum closing position (MCP), and (3) during the opening stroke. OCA at static maximum intercuspation (ICP) was also estimated.ResultsAt the MCP, the children's OCA was less than 76.4% of the contact area seen at the ICP. The timing of maximum OCA in children was shifted more towards the opening stroke compared with adults, and the OCA remained greater during opening in children than adults. The occurrence of the MCP was less stable in children than in adults, both between subjects and within subjects.ConclusionsWe conclude that both the amount of OCA and the pattern of occlusal contacts during the occlusal phase of chewing completely differ between children and adult females.     

Brain maturation in the first 3 months of life,measured by electroencephalogram: A comparison between preterm and term-born infants

ObjectivePreterm infants are at risk for altered brain maturation resulting in neurodevelopmental impairments. Topographical analysis of high-density electroencephalogram during sleep matches underlying brain maturation. Using such an EEG mapping approach could identify preterm infants at risk early in life.Methods20 preterm (gestational age < 32 weeks) and 20 term-born infants (gestational age > 37 weeks) were recorded by 18-channel daytime sleep-EEG at term age (GA 40 weeks for preterm and 2–3 days after birth for term infants) and 3 months (corrected age for preterm infants).ResultsPreterm infant’s power spectrum at term age is immature, leveling off with term infants at 3 months of age. Topographical distribution of maximal power density however, reveals qualitative differences between the groups until 3 months of age. Preterm infants exhibit more temporal than central activation at term age and more occipital than central activation at 3 months of age. Moreover, being less mature at term age predicts being less mature at 3 months of age.ConclusionTopographical analysis of sleep EEG reveals changes in brain maturation between term and preterm infants early in life.SignificanceIn future, automated analysis tools using topographical power distribution could help identify preterm infants at risk early in life.     

Updated Trends,Disparities, and Clinical Impact of Neuroimaging Utilization in Ischemic Stroke in the Medicare Population: 2012 to 2019

ObjectiveThe purpose of this study was to update trends, investigate sociodemographic disparities, and evaluate the impact on mortality of stroke neuroimaging across the United States from 2012 to 2019.MethodsRetrospective cohort study using CMS Medicare 5% Research Identifiable Files, representing consecutive ischemic stroke emergency department or hospitalized patients aged ≥65 years. A total of 85,547 stroke episodes with demographic and clinical information were analyzed using Cochran-Mantel-Haenszel tests and logistic regression. Outcome measures were neuroimaging (CT angiography [CTA], CT perfusion [CTP], MRI, MR angiography [MRA]) utilization, acute treatment (endovascular thrombectomy [EVT] and intravenous thrombolysis [IVT]), and mortality while in the hospital and at 30 days and 1 year post discharge.ResultsSignificantly increasing utilization trends for CTA (250%), CTP (428%) and MRI (18%), and a decreasing trend for MRA (?33%) were observed from 2012 to 2019 (P < .0001). Controlling for covariates in the logistic regression models, CTA and CTP were significantly associated with higher EVT and IVT utilization. Although CTA, MRI, and MRA were associated with lower mortality, CTP was associated with higher mortality post discharge. Less neuroimaging was performed in rural patients; older patients (≥80 years) had lower utilization of CTA, MRI, and MRA; female patients had lower rates of CTA; and Black patients had lower utilization of CTA and CTP.ConclusionsCTA and CTP utilization increased in the Medicare ischemic stroke population from 2012 to 2019 and both were associated with greater EVT and IVT use. However, disparities exist in neuroimaging utilization across all demographic groups, and further understanding of the root causes of these disparities will be crucial to achieving equity in stroke care.     

Management of sagittal craniosynostosis: morphological comparison of eight surgical techniques

The aim of this study was to carry out a retrospective multicentre study comparing the morphological outcome of 8 techniques used for the management of sagittal synostosis versus a large cohort of control patients. Computed tomographic (CT) images were obtained from children CT-scanned for non-craniosynostosis related events (n = 241) and SS patients at preoperative and postoperative follow-up stages (n = 101). No significant difference in morphological outcomes was observed between the techniques considered in this study. However, the majority of techniques showed a tendency for relapse. Further, the more invasive procedures at older ages seem to lead to larger intracranial volume compared to less invasive techniques at younger ages. This study can be a first step towards future multicentre studies, comparing surgical results and offering a possibility for objective benchmarking of outcomes between methods and centres.