Publication of data collection forms from NHLBI funded sickle cell disease implementation consortium (SCDIC) registry

Background: Sickle cell disease (SCD) is an autosomal recessive blood disorder affecting approximately 100,000 Americans and 3.1 million people globally. The scarcity of relevant knowledge and experience with rare diseases creates a unique need for cooperation and infrastructure to overcome challenges in translating basic research advances into clinical advances. Despite registry initiatives in SCD, the unavailability of descriptions of the selection process and copies of final data collection tools, coupled with incomplete representation of the SCD population hampers further research progress. This manuscript describes the SCDIC (Sickle Cell Disease Implementation Consortium) Registry development and makes the SCDIC Registry baseline and first follow-up data collection forms available for other SCD research efforts. Results: Study data on 2400 enrolled patients across eight sites was stored and managed using Research Electronic Data Capture (REDCap). Standardized data collection instruments, recruitment and enrollment were refined through consensus of consortium sites. Data points included measures taken from a variety of validated sources (PHENX, PROMIS and others). Surveys were directly administered by research staff and longitudinal follow-up was coordinated through the DCC. Appended registry forms track medical records, event-related patient invalidation, pregnancy, lab reporting, cardiopulmonary and renal functions. Conclusions: The SCDIC Registry strives to provide an accurate, updated characterization of the adult and adolescent SCD population as well as standardized, validated data collecting tools to guide evidence-based research and practice

Perinatal clinical antecedents of white matter microstructural abnormalities on diffusion tensor imaging in extremely preterm infants.

To identify perinatal clinical antecedents of white matter microstructural abnormalities in extremely preterm infants.A prospective cohort of extremely preterm infants (N = 86) and healthy term controls (N = 16) underwent diffusion tensor imaging (DTI) at term equivalent age. Region of interest-based measures of white matter microstructure - fractional anisotropy and mean diffusivity - were quantified in seven vulnerable cerebral regions and group differences assessed. In the preterm cohort, multivariable linear regression analyses were conducted to identify independent clinical factors associated with microstructural abnormalities.Preterm infants had a mean (standard deviation) gestational age of 26.1 (1.7) weeks and birth weight of 824 (182) grams. Compared to term controls, the preterm cohort exhibited widespread microstructural abnormalities in 9 of 14 regional measures. Chorioamnionitis, necrotizing enterocolitis, white matter injury on cranial ultrasound, and increasing duration of mechanical ventilation were adversely correlated with regional microstructure. Conversely, antenatal steroids, female sex, longer duration of caffeine therapy, and greater duration of human milk use were independent favorable factors. White matter injury on cranial ultrasound was associated with a five weeks or greater delayed maturation of the corpus callosum; every additional 10 days of human milk use were associated with a three weeks or greater advanced maturation of the corpus callosum.Diffusion tensor imaging is sensitive in detecting the widespread cerebral delayed maturation and/or damage increasingly observed in extremely preterm infants. In our cohort, it also aided identification of several previously known or suspected perinatal clinical antecedents of brain injury, aberrant development, and neurodevelopmental impairments

Independent antecedents of fractional anisotropy and mean diffusivity regional abnormalities from the EPI cohort identified in multiple regression analyses.

*<p>P<0.05,</p>**<p>P<0.01,</p>†<p>P<0.001.</p><p>(PLIC: posterior limb of internal capsule; FPVZ: frontal periventricular zone; OPVZ: occipital periventricular zone; CC: splenium and genu of corpus callosum; CS: centrum. semiovale; SVZ: subventricular zone; EC: external capsule; MCP: middle cerebellar peduncles).ALIC – anterior limb of internal capsule; PLIC – posterior limb of internal capsule; FPVZ – frontal periventricular zone; OPVZ – occipital periventricular zone; CC – corpus callosum; CS – centrum semiovale; SVZ – subventricular zone; EC – external capsule; MCP – middle cerebellar peduncles.</p

Demographic and clinical characteristics of participating infants.

*<p>P<0.05 and.</p>**<p>P<0.001 in comparison of term and EPI infants.</p>†<p>Defined as any presence of ventriculomegaly (with or without blood in the ventricles, blood/echodensity or cystic areas in the parenchyma, cystic periventricular leukomalacia, and/or porencephalic cyst evident on cranial US prior to 28 days of life.</p>‡<p>Defined as presence of signal abnormalities, brain atrophy, and/or abnormal gray matter or white matter maturation for age.</p

Study and control region of interest templates and placements shown on FA maps.

<p>Panel A: 1) Anterior limb of internal capsule, 2) Posterior limb of internal capsule, 3) Frontal periventricular zone, 4) Occipital periventricular zone, 5a–b) Centrum semiovale at two consecutive levels, 6 a–b) Genu and splenium of corpus callosum, and 7) Subventricular zone. Panel B: 1) External capsule, 2) Middle cerebellar peduncles. Same templates were utilized for all scans.</p

Comparison of mean (SD) fractional anisotropy (A) and mean diffusivity (SD) (B) between extremely preterm infants (light blue) and healthy term infants (navy) for seven study ROIs – ALIC, anterior limb of internal capsule, PLIC, posterior limb of internal capsule, FPVZ, frontal periventricular zone, OPVZ, occipital periventricular zone, CC, corpus callosum (genu and splenium), CS, centrum semiovale, SVZ, subventricular zone; and two control ROIs – EC, external capsule, MCP, middle cerebellar peduncles.

<p>*P<0.05 and **P<0.001.</p

Respiratory Medications in Infants &lt;29&nbsp;Weeks during the First Year Postdischarge: The Prematurity and Respiratory Outcomes Program (PROP) Consortium

ObjectiveTo determine patterns of respiratory medications used in neonatal intensive care unit graduates.Study designThe Prematurity Respiratory Outcomes Program enrolled 835 babies &lt;29&nbsp;weeks of gestation in the first week. Of 751 survivors, 738 (98%) completed at least 1, and 85% completed all 4, postdischarge medication usage in-person/telephone parental questionnaires requested at 3, 6, 9, and 12&nbsp;months of corrected age. Respiratory drug usage over the first year of life after in neonatal intensive care unit discharge was analyzed.ResultsDuring any given quarter, 66%-75% of the babies received no respiratory medication and 45% of the infants received no respiratory drug over the first year. The most common postdischarge medication was the inhaled bronchodilator albuterol; its use increased significantly from 13% to 31%. Diuretic usage decreased significantly from 11% to 2% over the first year. Systemic steroids (prednisone, most commonly) were used in approximately 5% of subjects in any one quarter. Inhaled steroids significantly increased over the first year from 9% to 14% at 12&nbsp;months. Drug exposure changed significantly based on gestational age with 72% of babies born at 23-24&nbsp;weeks receiving at least 1 respiratory medication but only 40% of babies born at 28&nbsp;weeks. Overall, at some time in the first year, 55% of infants received at least 1 drug including an inhaled bronchodilator (45%), an inhaled steroid (22%), a systemic steroid (15%), or diuretic (12%).ConclusionMany babies born at &lt;29&nbsp;weeks have no respiratory medication exposure postdischarge during the first year of life. Inhaled medications, including bronchodilators and steroids, increase over the first year

Bronchopulmonary Dysplasia and Perinatal Characteristics Predict 1-Year Respiratory Outcomes in Newborns Born at Extremely Low Gestational Age: A Prospective Cohort Study

OBJECTIVE:To assess the utility of clinical predictors of persistent respiratory morbidity in extremely low gestational age newborns (ELGANs). STUDY DESIGN:We enrolled ELGANs (&lt;29 weeks' gestation) at ≤7 postnatal days and collected antenatal and neonatal clinical data through 36 weeks' postmenstrual age. We surveyed caregivers at 3, 6, 9, and 12 months' corrected age to identify postdischarge respiratory morbidity, defined as hospitalization, home support (oxygen, tracheostomy, ventilation), medications, or symptoms (cough/wheeze). Infants were classified as having postprematurity respiratory disease (PRD, the primary study outcome) if respiratory morbidity persisted over ≥2 questionnaires. Infants were classified with severe respiratory morbidity if there were multiple hospitalizations, exposure to systemic steroids or pulmonary vasodilators, home oxygen after 3 months or mechanical ventilation, or symptoms despite inhaled corticosteroids. Mixed-effects models generated with data available at 1 day (perinatal) and 36 weeks' postmenstrual age were assessed for predictive accuracy. RESULTS:Of 724 infants (918 ± 234 g, 26.7 ± 1.4 weeks' gestational age) classified for the primary outcome, 68.6% had PRD; 245 of 704 (34.8%) were classified as severe. Male sex, intrauterine growth restriction, maternal smoking, race/ethnicity, intubation at birth, and public insurance were retained in perinatal and 36-week models for both PRD and respiratory morbidity severity. The perinatal model accurately predicted PRD (c-statistic 0.858). Neither the 36-week model nor the addition of bronchopulmonary dysplasia to the perinatal model improved accuracy (0.856, 0.860); c-statistic for BPD alone was 0.907. CONCLUSION:Both bronchopulmonary dysplasia and perinatal clinical data accurately identify ELGANs at risk for persistent and severe respiratory morbidity at 1 year. TRIAL REGISTRATION:ClinicalTrials.gov: NCT01435187