Multisite Cohort Study Research Articles

Mode of Delivery and Subsequent Motor Function in Children With Myelomeningocele Without In Utero Repair.

To assess the association between mode of delivery and 2-year motor function in children with prenatal diagnosis of myelomeningocele. A multisite retrospective cohort study of children with myelomeningocele across 14 NAFTNet (North American Fetal Therapy Network) centers born between 2007 and 2020 who had a physical examination available at 2 years of life. Exclusion criteria were in utero myelomeningocele repair, postnatal myelomeningocele diagnosis, missing data on fetal presentation at delivery, and contraindications to labor. The primary outcome was the difference between the anatomic level of the spinal lesion and functional motor level at age 2 years. A general linear model was used to determine the effect of mode of delivery on the primary outcome, and multivariable analysis was performed to control for presence of labor, gestational age at delivery, defect size and origin level, and presence of ventriculomegaly. Of 566 children with myelomeningocele, 305 met inclusion criteria, with 216 (70.8%) having been delivered by cesarean and 89 (29.2%) having been delivered vaginally. Children delivered by cesarean had a mean±SE level of motor function of 0.07±0.21 segments below the anatomic level at age 2 years compared with 0.57±0.32 for children delivered vaginally (P=.19). After controlling for potential confounders, both groups improved in motor function by age 2 years compared with anatomic level. However, there was no difference in motor improvement between groups by mode of delivery (0.07 cesarean vs 0.57 vaginal delivery, adjusted difference 0.37 segments, P=.63). In this multisite NAFTNet cohort, mode of delivery was not associated with lower-extremity motor function at age 2 years.

Glucagon-Like Peptide 1 Receptor Agonists and Risk of Thyroid Cancer: An International Multisite Cohort Study.

Introduction: Concerns have been raised that glucagon-like peptide 1 receptor agonists (GLP1-RAs) may increase the risk of thyroid cancer, but evidence remains conflicting. We therefore investigated if GLP1-RA use, compared with use of dipeptidyl peptidase-4 inhibitors (DPP-4is), was associated with thyroid cancer risk in patients with type 2 diabetes. Methods: This multisite cohort study with subsequent meta-analysis included six population-based databases from Canada (Ontario), Denmark, Norway, South Korea, Sweden, and Taiwan. Study populations comprised patients with type 2 diabetes between 2007 and 2023. Cox regression models estimated hazard ratios (HR) and 95% confidence intervals (CIs) for thyroid cancer among GLP1-RA users compared with DPP-4is. Models were weighted using standardized mortality ratio weights generated from time-specific propensity scores. Site-specific HRs were pooled using a fixed-effects model. Results: We identified 98,147 users of GLP1-RA and 2,488,303 users of DPP-4i, with the median follow-up among users of GLP1-RA ranging from 1.8 to 3.0 years. Overall, use of GLP1-RA relative to use of DPP-4i was not associated with an increased risk of thyroid cancer (pooled weighted HR 0.81, CI 0.59-1.12). Similarly, we observed no increased risk in thyroid cancer with increasing cumulative dose of GLP1-RA among GLP1-RA ever-users. Subgroup analysis of types of thyroid cancer was not possible. Results remained consistent across a range of supplementary analyses. Discussion: In this large multisite study, utilizing data from six population-based databases, we found no evidence that GLP1-RA use is associated with an increased risk of thyroid cancer with follow-up ranging from 1.8 to 3.0 years, providing some reassurance to patients and clinicians about the short-term safety of these drugs. Nevertheless, evidence was insufficient to rule out excess risk with long-term use, due to the short follow-up.

Establishing a model of peer support for pregnant persons with a substance use disorder as an innovative approach for engaging participants in the healthy brain and child development study.

The HEALthy Brain and Child Development (HBCD) Study, a multi-site prospective longitudinal cohort study, will examine human brain, cognitive, behavioral, social, and emotional development beginning prenatally and planned through early childhood. The goal is to recruit over 7000 caregiver-child dyads across the United States, with 25 % of the study population comprising children exposed in utero to substances to better understanding the effects of prenatal substance exposure on fetal and child development. However, barriers of mistrust for pregnant persons who are substance involved can create challenges to recruiting and retaining this population. The HBCD Study is utilizing a novel approach in research, the inclusion of support professionals (i.e. study navigators) as research team members to boost recruitment, engagement, and retention in this population and other marginalized and underrepresented groups. This article describes the conceptualization and early implementation of a support model utilizing certified peer support specialists, and the evolution to a broader study navigator model (SNM). Core skills, training, and support necessary for integrating such support professionals onto the research team are outlined. A reflection on challenges and next steps describes how the early implementation of the SNM encourages a paradigm shift in longitudinal research that humanizes and centers the participants.

Epidemiology of norovirus disease in the first 2 years of life: A prospective multisite cohort study in Lima, Peru.

Norovirus is associated with 18% of acute gastroenteritis (AGE) cases worldwide. We aim to document the norovirus-related AGE incidence in peri-urban areas of Lima (Peru), evaluating the potential impact of a norovirus vaccine introduction. A prospective, community-based pediatric cohort study was established at two sites in Lima. Healthy children between 5 and 18 months were contacted weekly for AGE detection during a 6-month period. Stool samples from AGE cases were tested for norovirus by RT-PCR. Incidence and coinfection of norovirus-associated AGE were analyzed. All norovirus-positive samples were genotyped by Sanger DNA sequencing. Among 498 enrolled children, 461 (93%) completed the follow-up period. We detected 799 AGE cases, yielding 676 valid stool samples. Norovirus was detected in 216 samples (32%), with an incidence of 7.7 episodes per 100 child-months (95% CI: 6.7-8.8). Genotypes GII.4 (31%) and GII.6 (22%) were frequent. Campylobacter (43%) and Salmonella spp. (15%) were the most common coinfections with norovirus. Ninety-five percent of study children had received an oral rotavirus vaccine. Norovirus was the second most frequent cause of AGE in this Peruvian cohort with high rotavirus vaccine coverage. An effective norovirus vaccine would have an important public health benefit in this population.

Impact of a Community-Based Health Intervention on Health Knowledge, Lifestyle Goals, Dietary Practices, and Physical Activity in Older Adults: A Multisite Cohort Study.

Background: Studies on the effectiveness of community-based health interventions (CBHIs) in improving lifestyle practices among older adults are limited. Objectives: This study evaluated the impact of a CBHI on health knowledge, lifestyle goal attainment, and practices among older adults in Singapore. Methods: Older adults (aged ≥60 years) were recruited from 29 senior recreation centres to participate in the "Wise and Well" programme, a 3-month CBHI designed to empower individuals to make healthier lifestyle choices. Pre- and post-programme assessments of health knowledge, goal attainment, and lifestyle behaviours (dietary practices and physical activity levels) were conducted using a health knowledge questionnaire, Goal Attainment Scaling (GAS), the Modified Dietary Practice Questionnaire (DPQ), and the Global Physical Activity Questionnaire (GPAQ), respectively. Statistical analysis was performed using the Wilcoxon signed-rank and McNemar's tests (α = 0.05). Results: The study comprised 464 participants (mean age 73.1 years [SD 7.6]; 75.9% women). Three months post-program, participants showed significantly increased health knowledge (p < 0.001) and improved lifestyle goal attainment (p < 0.001). Additionally, there was a significant increase in the proportion of participants meeting or exceeding fruit (p < 0.001) and vegetable (p = 0.002) intake recommendations and reductions in sugar-sweetened beverage consumption (p = 0.002). However, no significant changes were observed in fried food consumption or physical activity levels. High health knowledge scores were associated with 2.17 (95% confidence interval 1.02,4.64) times greater odds of increased vegetable intake. Conclusions: The CBHI shows potential as an effective approach to improving health knowledge and enhancing lifestyle goals and practices among older adults.

Impact of HIV exposure without infection on hospital course and mortality among young children in sub-Saharan Africa: a multi-site cohort study

BackgroundAlthough mortality risk associated with HIV is well described, HIV-exposed uninfected (HEU) young children are also at increased risk of hospitalization and death as compared to HIV-unexposed uninfected (HUU) children. The drivers of poor outcomes among HEU children remain unknown, limiting the development of interventions to support this vulnerable population.MethodsWe performed a secondary analysis of data from a large multi-country prospective cohort [Childhood Acute Illness and Nutrition (CHAIN) Network] study. Data from 5 sites in Uganda, Kenya, and Malawi were included. Hospitalized children aged 2–23 months were followed from an index admission for 6 months after discharge to determine acute and long-term outcomes. Using perinatal HIV exposure (HEU and HUU) as the primary exposure and adjusting for child, caregiver, and household characteristics, we compared inpatient and 30-day survival outcomes, nutritional status, hospital length of stay, illness severity, and utilization of inpatient resources.ResultsWe included 1486 children: 217 HEU and 1269 HUU. HEU children had an increased risk of mortality both during hospitalization [adjusted OR 1.96, 95% CI (1.14–3.37)] and in the 30 days following hospital admission [adjusted hazard ratio 2.20, 95% CI (1.10–4.42)]. Wasting and stunting were more frequent in HEU than HUU children, with adjusted OR 1.41, 95% CI (1.03–1.95) and adjusted OR 1.91, 95% CI (1.34–2.70), respectively. HEU children were also more likely to have a prolonged hospital stay compared to HUU children [adjusted OR 1.58, 95% CI (1.08–2.29)], although admission diagnoses, illness severity at admission, and use of inpatient resources (supplemental oxygen, nasogastric tube, and second-line antibiotics) did not differ significantly between groups.ConclusionsHEU children are more likely to die during hospitalization and within 30 days of admission, to be wasted and stunted upon hospital admission, and to require a prolonged hospital stay, as compared to HUU children. Hospitals in settings with a high prevalence of women-living-with-HIV should ensure that maternal HIV status is established among children requiring admission and build capacity to provide additional hospital monitoring and early post-discharge support for HEU children.

Monitoring drug Efficacy through Multi-Omics Research initiative in Alzheimer’s Disease (MEMORI-AD): A protocol for a multisite exploratory prospective cohort study on the drug response-related clinical, genetic, microbial and metabolomic signatures in Filipino patients with Alzheimer’s disease

IntroductionDementia is one of the leading causes of disability among older people aged 60 years and above, with majority eventually being diagnosed with Alzheimer’s disease (AD). Pharmacological agents approved for...

Salivary cortisol is not associated with dexamethasone response in preterm infants with evolving bronchopulmonary dysplasia.

Short-term treatment efficacy of systemic dexamethasone (DEX) in preterm infants with bronchopulmonary dysplasia (BPD) is highly variable. Our objective was to assess if salivary cortisol may serve as a reliable biomarker of steroid response. Multi-site prospective observational cohort study. Salivary cortisol was measured before and after DEX treatment. Respiratory Severity Score (RSS) quantified clinical response. Fifty-four infants with median (inter-quartile range) gestational age of 25.1 (24.1,26.5) weeks initiated DEX at 30 (23,48) days' postnatal age. Median baseline and post-treatment cortisol levels were 0.3 (0.2,0.6) μg/dl; 8.3 (5.5,16.5) nmol/L and 0.2 (0.1,0.3) μg/dl; 5.5 (2.8,8.3) nmol/L, respectively. RSS values decreased by a median of 3.1(1.6,5.0) Change in RSS did not correlate with baseline cortisol or change in cortisol levels. In this first study to assess salivary cortisol as a biomarker for DEX response in BPD, salivary cortisol did not predict dexamethasone response.

Operationalizing implementation science frameworks to plan a hybrid effectiveness-implementation study of a digital health intervention.

Evaluating implementation of digital health interventions (DHIs) in practice settings is complex, involving diverse users and multistep processes. Proactive planning can ensure desired implementation determinants and outcomes are captured for hybrid studies, but operational guidance for DHI studies is limited. We planned a cluster randomized, type II hybrid effectiveness-implementation trial testing PositiveLinks, a smartphone application for HIV care, compared to usual care (n = 6 sites per arm), among HIV outpatient sites in the DC Cohort Longitudinal HIV Study in Washington, DC. Our process included: 1) Defining components of the DHI and associated implementation strategy, 2) Selecting implementation science frameworks to accomplish evaluation aims, 3) Mapping framework dimensions, domains, and constructs to implementation strategy steps, 4) Modifying/creating instruments to collect data for implementation outcome measures and determinants and 5) Developing a compatible implementation science data collection and management plan. Specification of components of the DHI and implementation strategy identified relevant platform usage data and necessary implementer actions, toward planning measurement of program reach and adoption. A priori mapping of implementation strategy steps to the Reach Effectiveness Adoption Implementation Maintenance (RE-AIM) framework identified how data would be collected for each step/corresponding outcome measure. The multi-site cohort study provided infrastructure for prospective, scaled implementation research, including site research assistants (RAs) coordinating implementation. Existing cohort tools (periodic site assessments, patient consent logs) were adapted for the evaluation to further capture representativeness and reach/adoption 'denominators.' New survey instruments allowed for framework-guided evaluation of provider adaptations/dose/fidelity to planned implementation across a large number of participants and multiple timepoints. Some aspects of real-world implementation were challenging to mirror within the planned hybrid trial (e.g. RAs selected as de facto site implementation leads) or were modified to preserve internal validity of effectiveness measurement (e.g. PositiveLinks 'community of practice'). Challenges and opportunities arose in planning the implementation evaluation for PositiveLinks within a hybrid trial in a cohort population. Prospective hybrid trial planning must balance generalizability of implementation processes to 'real world' conditions, with rigorous trial procedures to measure intervention effectiveness. Rapid, scalable tools require further study to enable evaluations within large, multi-site hybrid studies.

¿Donde están? Hispanic/Latine inclusion, diversity and representation in the HEALthy Brain and Child Development Study (HBCD)

The HEALthy Brain and Child Development (HBCD) Study, a multi-site prospective longitudinal cohort study, will examine human brain, cognitive, behavioral, social, and emotional development beginning prenatally and planned through early childhood. Central to its mission of reducing health disparities is the establishment of the Spanish Language and Culture Committee (SLCC) within the HBCD framework, a significant step towards demographic representation and inclusivity in research. By addressing linguistic and sociocultural barriers and embracing the diverse identities of Hispanic/Latine individuals nationwide, the SLCC aims to promote inclusion, equity, and representation of all Hispanic/Latine subgroups, a population that has been historically misrepresented in health research. In this paper we describe the role of the SLCC in advocating for Hispanic/Latine families within the study, ensuring their inclusion from inception. This report also provides an overview of the SLCC organization, workflow, challenges and lessons learned thus far to reduce stigma and improve study outcomes, highlighting recruitment and retention strategies for the Hispanic/Latine population, and expanding outreach to promote inclusion across diverse Hispanic/Latine subgroups in the United States.

Abstract 4124226: Long-term exposure to air pollutants and incidence of cardiovascular disease events and mortality in The Multi-Ethnic Study of Atherosclerosis and Air Pollution (MESA Air)

Introduction: Exposure to ambient air pollution may increase the risk of cardiovascular disease events and mortality, but prior publications have primarily included administrative cohorts with outcomes that have not been individually reviewed and with air pollution estimates created without cohort-specific exposure monitoring. Multi-Ethnic Study of Atherosclerosis (MESA) is a multi-site cohort study designed specifically to prospectively collect and adjudicate cardiovascular disease (CVD) events. MESA Air recruited additional participants into sub-cohorts for enhanced air pollution variation and sample size. Research Question: The aim of this analysis was to characterize the relationship between long-term exposure to nitrogen dioxide (NO 2 ) and fine particulate matter (PM 2.5 ) and all-cause mortality and CVD events. Methods: Air pollution exposure was assessed using address history with a purpose-built exposure model incorporating cohort-specific monitoring including measurement and validation at participant homes. We used Cox models to assess the risk of rolling 2-year average exposures on all cause-mortality and on a composite CVD endpoint (definite angina, probable angina with revascularization, myocardial infarction, atherosclerosis or other CVD death, resuscitated cardiac arrest, and stroke). Models were stratified for baseline hazard by age, sub-cohort, and recruitment year and were additionally adjusted for age, sex, race/ethnicity, field center, smoking/second-hand smoke, pack-years, physical activity, education, income, neighborhood socioeconomic status, and statin use. Results: MESA Air participants were aged 44-87 years at enrollment between 2000 and 2007; follow-up averaged 14 years. 6,915 participants had follow-up for events, NO 2 exposure, and covariate information. We observed 1,442 deaths and 985 CVD events. The interquartile range over all 2-year averages was 10.5-23.1 ppb for NO 2 and 10.1-14.9 µ/m 3 for PM 2.5 . The adjusted hazard ratio (aHR) for a 10 ppb increment in NO 2 was 1.38 (95% CI: 1.17, 1.64) for all-cause mortality and 1.16 (95% CI: 0.95, 1.42) for incident CVD events. The aHR for a 5 µg/m 3 increment in PM 2.5 was 1.20 (95% CI: 0.99, 1.46) for all-cause mortality and 1.15 (95% CI: 0.95, 1.39) for incident CVD events Conclusions: These results add to growing literature demonstrating an association between air pollution exposure, mortality, and CVD in a cohort with well-characterized clinical endpoints and cohort-specific exposure assessment.

Maternal vitamin D status, fetal growth patterns, and adverse pregnancy outcomes in a multisite prospective pregnancy cohort

BackgroundFew studies have examined maternal vitamin D status and fetal growth patterns across gestation. Furthermore, time points in pregnancy at which maternal vitamin D status is most critical for optimal fetal growth and pregnancy outcomes are uncertain. ObjectivesOur objective was to examine whether first and second trimester maternal vitamin D status are associated with fetal growth patterns and pregnancy outcomes. MethodsWe conducted a secondary analysis using data and samples from a multisite prospective cohort study of nulliparous pregnant females in the United States. We measured serum 25-hydroxyvitamin D (25(OH)D) for 351 participants at 6–13 and 16–21 weeks of gestation. Fetal growth was measured by ultrasound at 16–21 and 22–29 weeks of gestation, and neonatal anthropometric measures at birth. We constructed fetal growth curves using length, weight, and head circumference z-scores, and calculated risk of preterm birth (<37 wk) and small for gestational age (SGA). We examined outcomes across 25(OH)D concentrations assessed continuously, using Institute of Medicine (IOM) cutoffs (<50 compared with ≥50 nmol/L), and using exploratory cutoffs (<40, 40–59.9, 60–79.9, ≥80 nmol/L). ResultsVitamin D insufficiency (25(OH)D <50 nmol/L) was prevalent in 20% of participants in the first trimester. Each 10 nmol/L increase in first trimester 25(OH)D was associated with a 0.05 [95% confidence interval (CI): 0.01, 0.10] increase in length-for-age z-score but was not associated with weight or head circumference. There were no differences in risk of preterm birth or SGA using IOM cutoffs; participants with first trimester 25(OH)D <40 compared with ≥80 nmol/L had 4.35 (95% CI: 1.14, 16.55) times risk of preterm birth. Second trimester 25(OH)D was not associated with fetal growth patterns or with pregnancy outcomes. ConclusionsFirst trimester 25(OH)D is positively associated with linear growth. Low first trimester 25(OH)D (<40 nmol/L) is associated with a higher risk of preterm birth. Second trimester 25(OH)D is not associated with fetal growth or pregnancy outcomes assessed.

The Impact of Clinical Features on Survival and Relapse of Patients Diagnosed With T-cell Acute Lymphoblastic Leukemia – a Multicenter Cohort Study

T-cell acute lymphoblastic leukemia (T-ALL) remains understudied compared to B-cell ALL, especially in Latin America. Different biology and response to chemotherapy have been described. This retrospective multi-site cohort study analyzed data from 152 newly diagnosed T-ALL patients aged 15 years and above, between January 2010 and June 2022. The median age was 30 years, with 53.9% of the patients presenting thymic T-ALL. Asparaginase-based regimens were used in 80.5% of patients. Five-year overall survival (OS) and event-free survival (EFS) were 44.3% and 41%, respectively. Thymic (CD1a) phenotype (HR 0.50 [0.28-0.89], P = .019) and asparaginase-based regimens (HR 0.53 [0.32-0.88], P = .014) were associated with improved OS, while older age predicted inferior OS (HR 1.02, P = .017). The 60-day cumulative incidence of thrombosis was 19.5% and induction death rate of 11.2%. The study provides real-world multicenter Brazilian data on adult T-ALL, which might represent Latin America's scenario, also highlights the benefits of pediatric-inspired regimens, especially for younger adults, key prognostic factors and that awareness is needed to manage thrombotic/death risks in the early treatment phases to improve outcomes.

Navigating ethical and legal challenges in the HEALthy Brain and Child Development Study: Lessons learned from the ethics, law, policy working group

The HEALthy Brain and Child Development (HBCD) Study, a multi-site prospective longitudinal cohort study, will examine human brain, cognitive, behavioral, social, and emotional development beginning prenatally and planned through early childhood. The HBCD study has faced several ethical and legal challenges due to its goal of enrolling pregnant people (including those with substance use disorder) and their newborns. Challenges not fully anticipated at the outset emerged from the rapidly changing legal landscape around reproductive rights in the United States. By embedding scholars in bioethics and law within research teams and engaging them in conversation with each other and other study personnel, we were able to address many challenges proactively and respond promptly to unanticipated challenges. In this paper, we highlight several important ethical and legal challenges that arose from the first phase of funding through the beginning of participant enrollment. We explain the methods used to address these challenges, the ethical and legal tradeoffs that arose, and the resolution of challenges through the design of the study. Based on this experience, we provide recommendations for research teams, sponsors, and reviewers to address legal risks and promote the ethical conduct of studies with pregnant people and caregivers. We highlight the importance of collaboration with bioethics and legal scholars in studies involving complex and evolving legal risks, as well as the necessity of designing robust approaches to informed consent and maintaining participant trust while navigating ethical challenges in research.

Unraveling the Associations Between Voice Pitch and Major Depressive Disorder: A Multisite Genetic Study.

Major depressive disorder (MDD) often goes undiagnosed due to the absence of clear biomarkers. We sought to identify voice biomarkers for MDD and separate biomarkers indicative of MDD predisposition from biomarkers reflecting current depressive symptoms. Using a two-stage meta-analytic design to remove confounds, we tested the association between features representing vocal pitch and MDD in a multisite case-control cohort study of Chinese women with recurrent depression. Sixteen features were replicated in an independent cohort, with absolute association coefficients (beta values) from the combined analysis ranging from 0.24 to 1.07, indicating moderate to large effects. The statistical significance of these associations remained robust, with P-values ranging from 7.2 × 10-6 to 6.8 × 10-58. Eleven features were significantly associated with current depressive symptoms. Using genotype data, we found that this association was driven in part by a genetic correlation with MDD. Significant voice features, reflecting a slower pitch change and a lower pitch, achieved an AUC-ROC of 0.90 (sensitivity of 0.85 and specificity of 0.81) in MDD classification. Our results return vocal features to a more central position in clinical and research work on MDD.

Multilevel Resilience and Appointment Attendance Among African American/Black Adults with HIV: A Prospective Multisite Cohort Study.

Attending clinic appointments supports HIV viral suppression, yet racial disparities are documented. We assessed whether multilevel resilience resources were associated with appointment attendance among African American/Black (AA/B) adults living with HIV in the United States. We ascertained data from 291 AA/B clinical cohort participants from 2018 to 2021. We assessed resilience using the Multilevel Resilience Resource Measure. Binary outcomes were a nonrepeated indicator of attending ≥87.5% of scheduled HIV appointments over 12 months (i.e., visit adherence) and a repeated measure of attending appointments during two sequential 6-month follow-up windows (i.e., clinic attendance). Modified Poisson models estimated adjusted risk ratios (aRRs). The aRR for clinic attendance among participants with greater versus lesser multilevel resilience resource endorsement was 0.95 (95% confidence interval: 0.88, 1.0). The aRR for visit adherence among participants with greater versus lesser multilevel resilience resource endorsement was 1.2 (0.95, 1.4). This analysis is one of the first to assess appointment attendance as a function of resilience. Findings should be confirmed in larger cohorts.

Prenatal detection of placenta accreta spectrum using a sonographic checklist.

The European Working Group for Abnormally Invasive Placenta proposed a checklist of ultrasound features for the antenatal detection of placenta accreta spectrum (PAS). This study aims to assess the performance of the checklist in identifying histopathologically confirmed PAS cases in a cohort with a high pre-test probability of PAS, and identify if particular features are associated with PAS. This is a prospective multi-site cohort study conducted between 2018 and 2023. Consecutive patients who underwent ultrasound assessment for suspicion of PAS were included, and the sonographic checklist was completed at the time of ultrasound. Cases were defined as PAS where they had intraoperative findings as described by the International Federation of Gynecology and Obstetrics (FIGO) grading, and histopathological findings for hysterectomy and myometrial resection cases. All non-PAS cases in this study had placenta previa and at least one prior cesarean delivery. Seventy-eight participants met inclusion criteria, of whom 63 (80.7%) were diagnosed with PAS. Cesarean hysterectomy was performed in 49 cases (62.8%). Overall, third-trimester ultrasound performed at a median gestational age of 32 weeks (IQR 30-34 weeks) had a sensitivity of 0.84 (95% CI 0.73 to 0.92) and specificity of 0.73 (95% CI 0.45 to 0.92) for detecting PAS, with a positive and negative likelihood ratio of 3.15 (95% CI 1.35 to 7.35) and 0.22 (95% CI 0.11 to 0.41), respectively. Features most associated with PAS were abnormal placental lacunae (Odds Ratio [OR] 5.40 [95% CI 1.61 to 18.03] and myometrial thinning OR 6.87 [95% CI 1.93 to 24.4]). While many of the ultrasound features seen in PAS were also present in cases of placenta previa with prior Cesarean section, the median (IQR) number of features present in PAS cases was significantly higher than in the non-PAS placenta previa group (six features [3-8] vs. two features [0-3] p = 0.001). No case of non-PAS placenta previa had more than five features present. The use of a standardized sonographic checklist had a high sensitivity and good specificity for the detection of PAS in this prospective cohort of well-classified PAS cases.

Diagnosis of renal tumors in Birt-Hogg-Dube syndrome: Clinical presentation and risk factors in a single-center retrospective cohort

BackgroundBirt-Hogg-Dube (BHD) syndrome is a rare genetic condition associated with the development of renal tumors. This study aims to determine typical age ranges for detecting renal abnormalities, risk factors for tumor development, and long-term outcomes based on current surveillance strategies.MethodsA single-center multi-site retrospective cohort study was performed on all patients with BHD diagnosed from 2000 to 2023. Baseline demographics, pulmonary function, laboratory, radiologic, and histopathologic findings were collected. Logistic regression was used to assess predictor variables for the development of renal tumors with survival analysis evaluated from the date of BHD diagnosis to date of death or last known follow-up.ResultsThe study included 149 patients with BHD, 39 (26%) with diagnosed renal tumors, of which 28 had histopathologic confirmation. Mean age at renal tumor detection was 53.61 years. Older age and male sex were predictive of renal tumor development ((odds ratio 1.05; 95% CI, 1.01–1.08, P = 0.002) and (odds ratio 2.59; 95% CI, 1.17–5.73, P = 0.02), respectively). Time to all-cause mortality appeared shorter in those with renal tumors (Log-rank P = 0.02), though no deaths were from cancer or cancer-related complications.ConclusionsCurrent screening protocols for renal tumors in BHD suggest the most common presenting age range for presentation is late 40s to early 50s, with older age and male sex as risk factors for tumor development.

Measurement of emerging neurocognitive and language skills in the HEALthy Brain and Child Development (HBCD) study

The HEALthy Brain and Child Development (HBCD) study, a multi-site prospective longitudinal cohort study, will examine human brain, cognitive, behavioral, social, and emotional development beginning prenatally and planned through early childhood. The study plans enrolling over 7000 families across 27 sites. This manuscript presents the measures from the Neurocognition and Language Workgroup. Constructs were selected for their importance in normative development, evidence for altered trajectories associated with environmental influences, and predictive validity for child outcomes. Evaluation of measures considered psychometric properties, brevity, and developmental and cultural appropriateness. Both performance measures and caregiver report were used wherever possible. A balance of norm-referenced global measures of development (e.g., Bayley Scales of Infant Development-4) and more specific laboratory measures (e.g., deferred imitation) are included in the HBCD study battery. Domains of assessment include sensory processing, visual-spatial reasoning, expressive and receptive language, executive function, memory, numeracy, adaptive behavior, and neuromotor. Strategies for staff training and quality control procedures, as well as anticipated measures to be added as the cohort ages, are reviewed. The HBCD study presents a unique opportunity to examine early brain and neurodevelopment in young children through a lens that accounts for prenatal exposures, health and socio-economic disparities.

Quantifying brain development in the HEALthy Brain and Child Development (HBCD) Study: The magnetic resonance imaging and spectroscopy protocol

The HEALthy Brain and Child Development (HBCD) Study, a multi-site prospective longitudinal cohort study, will examine human brain, cognitive, behavioral, social, and emotional development beginning prenatally and planned through early childhood. The acquisition of multimodal magnetic resonance-based brain development data is central to the study’s core protocol. However, application of Magnetic Resonance Imaging (MRI) methods in this population is complicated by technical challenges and difficulties of imaging in early life. Overcoming these challenges requires an innovative and harmonized approach, combining age-appropriate acquisition protocols together with specialized pediatric neuroimaging strategies. The HBCD MRI Working Group aimed to establish a core acquisition protocol for all 27 HBCD Study recruitment sites to measure brain structure, function, microstructure, and metabolites. Acquisition parameters of individual modalities have been matched across MRI scanner platforms for harmonized acquisitions and state-of-the-art technologies are employed to enable faster and motion-robust imaging. Here, we provide an overview of the HBCD MRI protocol, including decisions of individual modalities and preliminary data. The result will be an unparalleled resource for examining early neurodevelopment which enables the larger scientific community to assess normative trajectories from birth through childhood and to examine the genetic, biological, and environmental factors that help shape the developing brain.