Publications by authors named "Tina Cheng"

188 Publications

Outcomes of patients with solid tumour malignancies treated with first-line immuno-oncology agents who do not meet eligibility criteria for clinical trials.

Eur J Cancer 2021 Jul 8;151:115-125. Epub 2021 May 8.

Tom Baker Cancer Centre, University of Calgary, Calgary, AB, Canada. Electronic address:

Background: Immuno-oncology (IO)-based therapies have been approved based on randomised clinical trials, yet a significant proportion of real-world patients are not represented in these trials. We sought to compare the outcomes of trial-ineligible vs. -eligible patients with advanced solid tumours treated with first-line (1L) IO therapy.

Patients And Methods: Using the International Metastatic Renal Cell Carcinoma (RCC) Database Consortium and the Alberta Immunotherapy Database, patients with advanced RCC, non-small-cell lung cancer (NSCLC) or melanoma treated with 1L PD-(L)1 inhibition-based therapy were included. Trial eligibility was retrospectively determined as per commonly used exclusion criteria. The outcomes of interest were overall survival (OS), overall response rate (ORR), treatment duration (TD) and time to next treatment (TTNT).

Results: A total of 395 of 1241 (32%) patients were deemed trial-ineligible. The main reasons for ineligibility based on preselected exclusion criteria were Karnofsky performance status <70%/Eastern Cooperative Oncology Group performance status >1 (40%, 158 of 395), brain metastases (32%, 126 of 395), haemoglobin < 9 g/dL (16%, 63 of 395) and estimated glomerular filtration rate <40 mL/min (15%, 61 of 395). Between the ineligible vs. eligible groups, the median OS, ORR, median TD and median TTNT were 10.2 vs. 39.7 months (p < 0.01), 36% vs. 47% (p < 0.01), 2.7 vs. 6.9 months (p < 0.01) and 6.0 vs. 16.8 months (p < 0.01), respectively. Subgroup analyses showed statistically significant inferior OS, TD and TTNT for trial-ineligible vs. -eligible patients across all tumour types. Adjusted hazard ratios for death in RCC, NSCLC and melanoma were 1.84 (95% confidence interval [CI] 1.22-2.77), 2.21 (95% CI 1.58-3.11) and 1.82 (95% CI 1.21-2.74), respectively..

Conclusions: Thirty-two percent of real-world patients treated with contemporary 1L IO-based therapies were ineligible for clinical trials. Although one-third of the trial-ineligible patients responded to treatment, the overall trial-ineligible population had inferior outcomes than trial-eligible patients. These data may guide patient counselling and temper expectations of benefit.
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http://dx.doi.org/10.1016/j.ejca.2021.04.004DOI Listing
July 2021

The scope and severity of white-nose syndrome on hibernating bats in North America.

Conserv Biol 2021 Apr 20. Epub 2021 Apr 20.

West Virginia Division of Natural Resources, P.O. Box 67, Elkins, WV, 26241, U.S.A.

Assessing the scope and severity of threats is necessary for evaluating impacts on populations to inform conservation planning. Quantitative threat assessment often requires monitoring programs that provide reliable data over relevant spatial and temporal scales, yet such programs can be difficult to justify until there is an apparent stressor. Leveraging efforts of wildlife management agencies to record winter counts of hibernating bats, we collated data for 5 species from over 200 sites across 27 U.S. states and 2 Canadian provinces from 1995 to 2018 to determine the impact of white-nose syndrome (WNS), a deadly disease of hibernating bats. We estimated declines of winter counts of bat colonies at sites where the invasive fungus that causes WNS (Pseudogymnoascus destructans) had been detected to assess the threat impact of WNS. Three species undergoing species status assessment by the U.S. Fish and Wildlife Service (Myotis septentrionalis, Myotis lucifugus, and Perimyotis subflavus) declined by more than 90%, which warrants classifying the severity of the WNS threat as extreme based on criteria used by NatureServe. The scope of the WNS threat as defined by NatureServe criteria was large (36% of Myotis lucifugus range) to pervasive (79% of Myotis septentrionalis range) for these species. Declines for 2 other species (Myotis sodalis and Eptesicus fuscus) were less severe but still qualified as moderate to serious based on NatureServe criteria. Data-sharing across jurisdictions provided a comprehensive evaluation of scope and severity of the threat of WNS and indicated regional differences that can inform response efforts at international, national, and state or provincial jurisdictions. We assessed the threat impact of an emerging infectious disease by uniting monitoring efforts across jurisdictional boundaries and demonstrated the importance of coordinated monitoring programs, such as the North American Bat Monitoring Program (NABat), for data-driven conservation assessments and planning.
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http://dx.doi.org/10.1111/cobi.13739DOI Listing
April 2021

Pediatric research today and tomorrow post-COVID-19.

Pediatr Res 2021 Apr 13. Epub 2021 Apr 13.

Department of Pediatrics, David Geffen School of Medicine at University of California, Los Angeles, CA, USA.

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http://dx.doi.org/10.1038/s41390-021-01520-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8042618PMC
April 2021

The "Cs" of Mentoring: Using Adult Learning Theory and the Right Mentors to Position Early-Career Investigators for Success.

J Pediatr 2021 Mar 20. Epub 2021 Mar 20.

Cincinnati Children's Hospital Medical Center, Cincinnati, OH; University of Cincinnati College of Medicine, Cincinnati, OH. Electronic address:

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http://dx.doi.org/10.1016/j.jpeds.2021.03.023DOI Listing
March 2021

Evaluation of the modified immune prognostic index to prognosticate outcomes in metastatic uveal melanoma patients treated with immune checkpoint inhibitors.

Cancer Med 2021 04 16;10(8):2618-2626. Epub 2021 Mar 16.

Tom Baker Cancer Centre, University of Calgary, Calgary, AB, Canada.

Background: Metastatic uveal melanoma (MUM) is associated with poor survival and inferior response to immune checkpoint inhibitor (ICI) therapy when compared with metastatic cutaneous melanoma. Currently, prognostic biomarkers are lacking to guide treatment decisions.

Patients And Methods: We conducted a multicenter, retrospective cohort study using a centralized, province-wide cancer database in Alberta, Canada. We identified 37 patients with histologically confirmed MUM who received at least one dose of single-agent pembrolizumab or nivolumab, or combination therapy nivolumab and ipilimumab. A modified immune prognostic index (IPI), based on the previously reported lung immune prognostic index, was used to stratify patients into favorable and poor IPI groups. Survival analyses were conducted using the Kaplan-Meier method and Cox proportional hazards models, adjusting for baseline age (≥60) and ECOG performance status, to assess the associations between IPI and overall survival (OS). Time to treatment failure (TTF) was also assessed using the Kaplan-Meier method. The association between IPI and objective response rate was examined using chi-squared tests. Logistic regression was used to determine the association between IPI and immune-related adverse events (irAEs).

Results: Median OS was 15.6 (range 0.6-57.6) months with 45.9% 1-year survival rate at a median follow-up of 11.8 months. We found that a favorable IPI was significantly associated with OS [median 30.5 (12.0-not reached) months in the favorable IPI group compared with 4.6 (2.1-16.0) months in the poor IPI group (p = 0.001)] (HR=4.81, 95% CI; 1.64-14.10, p = 0.004), TTF [median 5.1 (95% CI; 2.1-10.4) months in the favorable IPI group compared with 3.7 (95% CI; 1.4-6.4) months in the poor IPI group (p = 0.0191)], and irAE (HR=6.67, 95% CI; 1.32-33.69, p = 0.0220).

Conclusions: The modified IPI may be a useful tool in clinical practice for identifying MUM patients who are more likely to experience irAEs and realize a survival benefit from ICI treatment.
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http://dx.doi.org/10.1002/cam4.3784DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8026925PMC
April 2021

NABat: A top-down, bottom-up solution to collaborative continental-scale monitoring.

Ambio 2021 Apr 17;50(4):901-913. Epub 2021 Jan 17.

USDA Forest Service, Pacific Southwest Research Station, Arcata, CA, USA.

Collaborative monitoring over broad scales and levels of ecological organization can inform conservation efforts necessary to address the contemporary biodiversity crisis. An important challenge to collaborative monitoring is motivating local engagement with enough buy-in from stakeholders while providing adequate top-down direction for scientific rigor, quality control, and coordination. Collaborative monitoring must reconcile this inherent tension between top-down control and bottom-up engagement. Highly mobile and cryptic taxa, such as bats, present a particularly acute challenge. Given their scale of movement, complex life histories, and rapidly expanding threats, understanding population trends of bats requires coordinated broad-scale collaborative monitoring. The North American Bat Monitoring Program (NABat) reconciles top-down, bottom-up tension with a hierarchical master sample survey design, integrated data analysis, dynamic data curation, regional monitoring hubs, and knowledge delivery through web-based infrastructure. NABat supports collaborative monitoring across spatial and organizational scales and the full annual lifecycle of bats.
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http://dx.doi.org/10.1007/s13280-020-01411-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7982360PMC
April 2021

A Nonlinear Relation Between Maternal Red Blood Cell Manganese Concentrations and Child Blood Pressure at Age 6-12 y: A Prospective Birth Cohort Study.

J Nutr 2021 03;151(3):570-578

Center on the Early Life Origins of Disease, Department of Population, Family and Reproductive Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.

Background: Although manganese (Mn) is an essential trace element and a common component of most multivitamins on the market, an adverse effect on blood pressure (BP) has been reported in adults. In addition, the longitudinal relation between prenatal Mn status and childhood BP is still unknown.

Objective: This study investigated the association between prenatal Mn concentrations and risk of elevated BP at ages 3-12 y.

Method: The analyses included 1268 mother-child dyads who were enrolled at birth and followed prospectively at the Boston Medical Center. Maternal RBC Mn concentrations were measured by inductively coupled plasma mass spectrometry, using RBCs collected within 1-3 d after delivery (reflecting late-pregnancy Mn exposure). Child elevated BP was defined as systolic or diastolic BP ≥90th percentile for a given age, sex and height. Multivariate logistic regression models were conducted. Path analysis was applied to mediation estimation.

Results: The median (IQR) maternal RBC Mn concentration was 37.5 (29.2-48.5) μg/L. The rate of child elevated BP at ages 3-12 y was 25%. Both the lowest and highest quartiles of maternal RBC Mn concentrations were associated with higher risk of elevated BP among children aged 6-12 y (OR: 1.52; 95% CI: 1.04, 2.21 and OR: 1.65; 95% CI: 1.13, 2.40, respectively) compared with those in the second and third quartiles. Gestational age and fetal growth mediated the association between low maternal RBC Mn (first quartile) and child elevated BP, explaining 25% of the association, but not for high (fourth quartile) maternal RBC Mn concentrations. No association was found between maternal RBC Mn concentrations and BP among children aged 3-5 y.

Conclusion: We found a nonlinear association between maternal RBC Mn concentrations and elevated BP among children aged 6-12 y from a high-risk, predominantly minority population. Our findings warrant further investigation.
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http://dx.doi.org/10.1093/jn/nxaa368DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7948198PMC
March 2021

Factors associated with successful mentor matching in an intervention study of youth violence.

J Community Psychol 2021 Jan 7. Epub 2021 Jan 7.

Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

One challenge of conducting intervention studies is ensuring that study participants are exposed to the intervention. For example, in our randomized controlled trial of Take Charge!, a mentor-implemented and research-informed violence prevention program that partners with one-on-one community-based mentoring agencies, only 50% of intervention youth with fight-related injuries were successfully matched with a mentor. We examined the differences between matched (n = 49) and unmatched (n = 49) youth with regard to demographics, time from injury to study enrollment, perceived seriousness of injury, belief that future injury can be avoided, and household chaos. Youth who were successfully matched with a mentor were more likely to perceive the injury as very serious or somewhat serious compared with unmatched youth (95.9% vs. 79.6%, p = .028). All other factors were not significantly associated with successful mentor matching. Future violence prevention interventions should consider youth perceptions as a factor that may influence the completion of desired interventions.
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http://dx.doi.org/10.1002/jcop.22503DOI Listing
January 2021

Maternal Hypertensive Disorders in Pregnancy and Postpartum Plasma B Vitamin and Homocysteine Profiles in a High-Risk Multiethnic U.S., Population.

J Womens Health (Larchmt) 2020 12 16;29(12):1520-1529. Epub 2020 Nov 16.

Department of Population, Family and Reproductive Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA.

Hypertensive disorders of pregnancy are a recognized risk factor of a woman's future cardiovascular risk. The potential role of micronutrients in mitigating hypertensive disorders is not fully understood. This study examined maternal postpartum plasma B vitamin profiles by hypertensive disorders of pregnancy in a high-risk multiethnic U.S. population. The analyses included 2584 mothers enrolled within 3 days postpartum at the Boston Medical Center. Hypertensive disorders of pregnancy included gestational hypertension and pre-eclampsia disorders (pre-eclampsia, eclampsia, hemolysis, elevated liver enzymes, and/or low platelets syndrome) as documented in the medical records. Plasma folate, vitamin B12, and homocysteine levels were measured in blood samples collected at enrollment. Kernel density plots and multivariable regressions were used to examine the relationship between hypertensive disorders and postpartum B vitamin profiles. Of the 2584 mothers, 10% had pre-eclampsia disorders that were associated with significantly lower plasma folate (adjusted beta coefficient (aβ): -0.10; 95% CI: -0.22 to -0.06) and increased homocysteine (aβ: 0.08; 95% CI: 0.04-0.13), but not with vitamin B12 concentrations. These associations remained robust after adjusting for a range of pertinent covariables and were more pronounced in non-Hispanic Black women compared with other groups. However, gestational hypertension was not significantly associated with any postpartum biomarker. We found that pre-eclampsia disorders, but not gestational hypertension, was associated with lower folate and higher homocysteine levels postpartum, especially among Black mothers. This finding, if further confirmed, may have implications for postpartum care, including attention to maternal micronutrient status to reduce and prevent hypertensive disorders in pregnancy-associated consequences in subsequent pregnancies and lifespan. Registration date: July 25, 2017; Registry website: https://clinicaltrials.gov/ct2/show/NCT03228875.
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http://dx.doi.org/10.1089/jwh.2020.8420DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7757544PMC
December 2020

A Risk-benefit Analysis of Prophylactic Anticoagulation for Patients with Metastatic Germ Cell Tumours Undergoing First-line Chemotherapy.

Eur Urol Focus 2020 Oct 6. Epub 2020 Oct 6.

Hematology Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address:

Background: It remains unclear which patients with metastatic germ cell tumours (mGCTs) need prophylactic anticoagulation to prevent venous thromboembolic events (VTEs).

Objective: To assess the risk and onset of VTEs stratified by risk factors.

Design, Setting, And Participants: This multi-institutional retrospective dataset included mGCT patients treated with first-line platinum-based chemotherapy.

Intervention: Patients with prophylactic anticoagulation were excluded.

Outcome Measurements And Statistical Analysis: A regression analysis was performed to select risk factors for VTEs. The simulated number needed to treat (NNT) and the number needed to harm (NNH) with prophylactic anticoagulation were calculated based on the cumulative incidences retrieved from this study and hazard rates of recently published trials describing the efficacy of prophylactic anticoagulation to prevent VTEs and the risk of bleeding events.

Results And Limitations: From 1120 patients, 121 (11%) had a VTE, which occurred prior to chemotherapy in 49 (4%) and on or after chemotherapy in 72 (6%). Six patients (<1%) had a bleeding event without anticoagulation. After backward regression, the one risk factor for a VTE during or after chemotherapy was the use of a venous access device. The simulated cumulative VTE incidence from prophylactic anticoagulation for patients on or after chemotherapy would translate into an NNT of 45 (95% confidence interval [CI] 36-56) and an NNH of 186 (95% CI 87-506). Limitations are mainly related to the retrospective nature of the study.

Conclusions: The mGCTs associated VTEs are most common before and during, but not after, chemotherapy. Avoiding venous access device and/or prophylactic anticoagulation with an acceptable risk-benefit profile may decrease VTE occurring on chemotherapy.

Patient Summary: We found that venous thromboembolic events (VTEs) occur rarely after chemotherapy. Based on experience of prophylactic anticoagulation in other cancers, we conclude that the risk of VTE in men undergoing chemotherapy for metastatic germ cell tumours can be decreased by thromboprophylaxis with a reasonable risk-benefit profile and by avoidance of venous access devices.
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http://dx.doi.org/10.1016/j.euf.2020.09.017DOI Listing
October 2020

The Pandemics of Racism and COVID-19: Danger and Opportunity.

Pediatrics 2020 11 1;146(5). Epub 2020 Sep 1.

Warren Alpert Medical School, Brown University, Providence, Rhode Island.

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http://dx.doi.org/10.1542/peds.2020-024836DOI Listing
November 2020

Shoring up the safety net for children in the COVID-19 pandemic.

Pediatr Res 2020 09 26;88(3):349-351. Epub 2020 Jul 26.

Department of Pediatrics, University of Missouri-Kansas City School of Medicine, Kansas City, MO, USA.

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http://dx.doi.org/10.1038/s41390-020-1071-7DOI Listing
September 2020

Family-Oriented Social Service Touchpoints as Opportunities to Enhance Diabetes Screening following a History of Gestational Diabetes.

J Am Board Fam Med 2020 Jul-Aug;33(4):616-619

From the Division of General Internal Medicine, Johns Hopkins University School of Medicine, Baltimore, MD (MV, HCY, WLB, NMM); Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD (MV, TLC, NMM); Welch Center for Prevention, Epidemiology and Clinical Research, Baltimore, MD (MV, HCY, WB, NMM); Johns Hopkins Brancati Center for the Advancement of Community Care, Baltimore, MD (MV, NMA).

Introduction: Women with a history of gestational diabetes (GDM) are at increased risk for type 2 diabetes and thus require regular follow-up screening for diabetes; however, many women do not receive this screening, and in particular low-income women face disparities in receipt of recommended follow-up care. While these women may have limited access to healthcare following pregnancy, they may more regularly access social service programs that serve themselves or their young children. Leveraging these social service touchpoints could broaden opportunities to improve follow-up care receipt among women with a history of GDM. To describe these potential opportunities, we used national representative data to characterize diabetes screening needs among women with a history of GDM who access the Special supplemental nutrition program for Women, Infants and Children (WIC) or Head Start programming for their young children.

Methods: We analyzed national representative data from the National Health Interview Survey from calendar years 2016 and 2017. Our analytic sample included women aged 18 to 45 years who were linked to at least one of their children in the dataset and who had a self-reported history of GDM but did not have prediabetes or diabetes. We examined the proportion of these women who accessed WIC or Head Start who did not report having testing for diabetes within the past 3 years.

Results: Of 432 (representing 2,002,675 weighted) women meeting inclusion criteria, 21.7% accessed WIC and 8.7% Head Start. Nearly 1 in 10 women with a history of GDM in either group did not report recent diabetes screening. In sensitivity analyses that excluded likely pregnancy-related testing, 35.0% of women accessing WIC and 21.2% of those accessing Head Start had not had recent screening.

Discussion: There is an unmet need for follow-up diabetes screening among women with a history of GDM who access WIC or Head Start services for their young children. Leveraging women's touchpoints with these programs could enhance opportunities to improve recommended diabetes screening among a high-risk population.
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http://dx.doi.org/10.3122/jabfm.2020.04.190382DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7836091PMC
October 2019

Machine learning for prediction of cutaneous adverse events in patients receiving anti-PD-1 immunotherapy.

J Am Acad Dermatol 2021 Jan 22;84(1):183-185. Epub 2020 Apr 22.

Department of Oncology, University of Calgary, Ontario, Canada. Electronic address:

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http://dx.doi.org/10.1016/j.jaad.2020.04.069DOI Listing
January 2021

Family Values Means Covering Families: Parents Need to Focus on Parenting, Not Access to Care.

Pediatrics 2020 05 15;145(5). Epub 2020 Apr 15.

Department of Pediatrics, School of Medicine.

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http://dx.doi.org/10.1542/peds.2020-0401DOI Listing
May 2020

Anti-PD1-Induced Immune-Related Adverse Events and Survival Outcomes in Advanced Melanoma.

Oncologist 2020 05 12;25(5):438-446. Epub 2020 Feb 12.

Department of Oncology, University of Calgary, Calgary, Alberta, Canada.

Introduction: Objective response rates (ORR) appear to be higher in melanoma patients who develop immune-related adverse events (irAEs), but whether there is a similar association between irAEs and survival remains unknown.

Materials And Methods: Patients with advanced melanoma treated with single-agent pembrolizumab or nivolumab in the province of Alberta from June 2014 to May 2017 were identified through the provincial pharmacy database. Chart review identified and categorized all irAEs that occurred while on anti-programmed cell death protein 1 (PD-1) checkpoint inhibitors. The primary objective was to compare overall survival (OS) with patients who developed any irAEs versus those who did not. Secondary outcomes included progression-free survival (PFS) and ORR.

Results: Among 186 patients, any-grade and grade ≥3 irAEs occurred in 88 (47%) and 27 (15%) patients, respectively; one patient died of pneumonitis. In a landmark analysis excluding patients who died within the first 12 weeks, the median follow-up was 24 months, 20 months in patients without any irAEs and 26 months in patients with irAEs (p = .006). Median OS was 39 versus 23 months (hazard ratio [HR], 0.46; p = .001) for any irAE and no irAE, respectively, and median OS not reached versus 29 months for grade ≥3 irAEs and no grade ≥3 irAEs, respectively. In multivariate analysis, elevated lactate dehydrogenase correlated with reduced OS (HR, 2.34; p = .001), whereas each additional cycle of treatment received (HR, 0.94; p < .001) and development of grade ≥3 irAEs (HR, 0.29, p = .024) were significantly associated with longer OS.

Conclusion: Anti-PD-1-associated grade ≥3 irAEs in patients with advanced melanoma is associated with better patient outcomes, including overall survival.

Implications For Practice: Previous prospective randomized clinical trials demonstrate improved response rates in patients with melanoma who develop select adverse events. The current population-based real-world study in advanced melanoma reports an association with anti-programmed cell death protein 1 (PD-1)-induced grade ≥3 immune-related adverse events (irAEs) and better patient outcomes, including overall survival. These results suggest that irAEs may be a manifestation of a patient's ability to mount a systemic immune response from PD-1-directed therapies, which may be associated with therapeutic benefit. The finding of irAEs coinciding with clinical benefit from these therapies supposes that these events are, by and large, unavoidable, and the critical management of irAEs remains essential for optimizing patient outcomes.
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http://dx.doi.org/10.1634/theoncologist.2019-0674DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7216458PMC
May 2020

Prevalence and risk factors of polycystic ovarian syndrome among an ethnically diverse overweight/obese adolescent population.

Int J Adolesc Med Health 2020 Jan 11. Epub 2020 Jan 11.

Adolescent Clinic, Department of Pediatrics, Icahn School of Medicine at Mount Sinai/Elmhurst Hospital Center, Elmhurst, NY, USA.

Background More remains to be known about polycystic ovary syndrome (PCOS) among overweight/obese adolescents across different ethnicities especially in regards to mental illness as an associated comorbidity. Objective To determine the prevalence of PCOS among overweight and obese adolescents and to evaluate known risk factors for PCOS in a diverse population. Methods Charts of patients at an Adolescent Clinic between April 1, 2016 and July 30, 2018 were filtered using: obese, overweight and body mass index (BMI) >85%. Charts were reviewed to identify the presence of PCOS using National Institutes of Health (NIH) criteria, race/ethnicity and known risk factors for PCOS [lipid, BMI, glycated hemoglobin (HA1c), blood pressure (BP)] and mental health conditions associated with PCOS (anxiety/depression and self-harm/suicidal ideation). Results Patients with PCOS were more likely to have elevated lipids (19.6% vs. 9.9%, p = 0.05), be obese (67.4% vs. 50.9%, p = 0.03), and have acanthosis nigricans (68.9% vs. 28.2%, p =< 0.001). PCOS was more common among non-Hispanic patients (77.9%) vs. Hispanic patients (57.8%). There was no difference in the prevalence of depression/anxiety (37% vs. 33%, respectively, p = 0.590) or self - harm/suicidal ideation (17% vs. 17%, p = 0.96) in patients with and without PCOS. In a logistic regression model, after adjusting for all demographics and clinical features, ethnicity, acanthosis nigricans and BMI were significant risk factors for PCOS. Conclusion Patients with PCOS are more likely to be obese, hyperlipidemic, have acanthosis nigricans and be of non-Hispanic ethnicity. However, there was no difference in the prevalence of depression/anxiety and self-harm/suicidal ideation among adolescents with or without PCOS.
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http://dx.doi.org/10.1515/ijamh-2019-0109DOI Listing
January 2020

Enabling Factors Associated with Receipt of Interconception Health Care.

Matern Child Health J 2020 Mar;24(3):275-282

Department of Pediatrics, Johns Hopkins School of Medicine, Baltimore, MD, USA.

Objectives: Preventive health care between pregnancies may benefit future pregnancies and women's long-term health, yet such care is frequently incomplete. We used Andersen's Model of Health Services Use to identify factors associated with receipt of interconception care.

Methods: This secondary analysis uses data from a trial that recruited women from four health centers in the Baltimore metropolitan area. We used data on factors associated with Andersen's model reported up to 15 months postpartum. Factors included health history (diabetes, hypertension, prematurity), self-rated health, demographics (age, race/ethnicity, education, marital status, employment, income, parity), predisposing factors (depression, stress, social support), and enabling factors (usual place of care, personal doctor or nurse, insurance). Relative risk regression modeled the relationship between these factors and a dependent variable defined as completing both a postpartum visit and one subsequent health care visit. Models also accounted for time since birth, clustering by site, and trial arm.

Results: We included 376 women followed a mean of 272 days postpartum (SD 57), of whom 226 (60%) completed a postpartum and subsequent visit. Women were predominantly non-Hispanic Black (84%) and low income (50% household income < $20,000/year). In regression, two enabling factors were associated with increased receipt of care: having a personal doctor or nurse (RR 1.38, 95% CI 1.11-1.70) and non-Medicaid insurance (RR 1.64, 95% CI 1.09-2.56).

Conclusions For Practice: Enabling factors were associated with receipt of recommended care following birth. These factors may be modifiable components of efforts to improve care during this critical life course period.
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http://dx.doi.org/10.1007/s10995-019-02850-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7117827PMC
March 2020

In utero exposure to mercury and childhood overweight or obesity: counteracting effect of maternal folate status.

BMC Med 2019 11 28;17(1):216. Epub 2019 Nov 28.

Department of Population, Family and Reproductive Health, Center on the Early Life Origins of Disease, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, Baltimore, MD, 21205-2179, USA.

Background: Low-dose mercury (Hg) exposure has been associated with cardiovascular diseases, diabetes, and obesity in adults, but it is unknown the metabolic consequence of in utero Hg exposure. This study aimed to investigate the association between in utero Hg exposure and child overweight or obesity (OWO) and to explore if adequate maternal folate can mitigate Hg toxicity.

Methods: This prospective study included 1442 mother-child pairs recruited at birth and followed up to age 15 years. Maternal Hg in red blood cells and plasma folate levels were measured in samples collected 1-3 days after delivery (a proxy for third trimester exposure). Adequate folate was defined as plasma folate ≥ 20.4 nmol/L. Childhood OWO was defined as body mass index ≥ 85% percentile for age and sex.

Results: The median (interquartile range) of maternal Hg levels were 2.11 (1.04-3.70) μg/L. Geometric mean (95% CI) of maternal folate levels were 31.1 (30.1-32.1) nmol/L. Maternal Hg levels were positively associated with child OWO from age 2-15 years, independent of maternal pre-pregnancy OWO, diabetes, and other covariates. The relative risk (RR = 1.24, 95% CI 1.05-1.47) of child OWO associated with the highest quartile of Hg exposure was 24% higher than those with the lowest quartile. Maternal pre-pregnancy OWO and/or diabetes additively enhanced Hg toxicity. The highest risk of child OWO was found among children of OWO and diabetic mothers in the top Hg quartile (RR = 2.06; 95% CI 1.56-2.71) compared to their counterparts. Furthermore, adequate maternal folate status mitigated Hg toxicity. Given top quartile Hg exposure, adequate maternal folate was associated with a 34% reduction in child OWO risk (RR = 0.66, 95% CI 0.51-0.85) as compared with insufficient maternal folate. There was a suggestive interaction between maternal Hg and folate levels on child OWO risk (p for interaction = 0.086).

Conclusions: In this US urban, multi-ethnic population, elevated in utero Hg exposure was associated with a higher risk of OWO in childhood, and such risk was enhanced by maternal OWO and/or diabetes and reduced by adequate maternal folate. These findings underscore the need to screen for Hg and to optimize maternal folate status, especially among mothers with OWO and/or diabetes.
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http://dx.doi.org/10.1186/s12916-019-1442-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6882077PMC
November 2019

High content analysis of granuloma histology and neutrophilic inflammation in adult zebrafish infected with Mycobacterium marinum.

Micron 2020 Feb 13;129:102782. Epub 2019 Nov 13.

Tuberculosis Research Program at the Centenary Institute, The University of Sydney, Camperdown, NSW, 2050, Australia; The University of Sydney, Discipline of Infectious Diseases & Immunology and Marie Bashir Institute, Camperdown, NSW, 2050, Australia. Electronic address:

Infection of zebrafish with natural pathogen Mycobacterium marinum is a useful surrogate for studying the human granulomatous inflammatory response to infection by Mycobacterium tuberculosis. The adaptive immune system of the adult stage zebrafish offers an advance on the commonly used embryo infection model as adult zebrafish form granulomas with striking similarities to human-M. tuberculosis granulomas. Here, we present workflows to perform high content analyses of granulomas in adult zebrafish infected with M. marinum by cryosectioning to take advantage of strong endogenous transgenic fluorescence adapted from common zebrafish embryo infection tools. Specific guides to classifying granuloma necrosis and organisation, quantifying bacterial burden and leukocyte infiltration of granulomas, visualizing foam cell formation, analysing extracellular matrix remodelling and granuloma fibrosis are also provided. We use these methods to characterize neutrophil recruitment to M. marinum granulomas across time and find an inverse relation to granuloma necrosis suggesting granuloma necrosis is not a marker of immunopathology in the natural infection system of the adult zebrafish-M. marinum pairing. The methods can be easily translated to studying the zebrafish adaptive immune response to other chronic and granuloma-forming pathogens.
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http://dx.doi.org/10.1016/j.micron.2019.102782DOI Listing
February 2020

Large retroperitoneal lymphadenopathy and increased risk of venous thromboembolism in patients receiving first-line chemotherapy for metastatic germ cell tumors: A study by the global germ cell cancer group (G3).

Cancer Med 2020 01 12;9(1):116-124. Epub 2019 Nov 12.

Division of Medical Oncology and Hematology, Department of Medicine, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada.

Background: Metastatic germ cell tumor (mGCT) patients receiving chemotherapy have increased risk of life-threatening venous thromboembolism (VTE). Identifying VTE risk factors may guide thromboprophylaxis in this highly curable population.

Methods: Data were collected from mGCT patients receiving first-line platinum-based chemotherapy at 22 centers. Predefined variables included International Germ Cell Cancer Collaborative Group (IGCCCG) risk classification, long-axis diameter of largest retroperitoneal lymph node (RPLN), Khorana score, and use of indwelling vascular access device (VAD). VTE occurring at baseline, during chemotherapy and within 90 days, was analyzed.

Results: Data from 1135 patients were collected. Median age was 31 years (range 10-74). IGCCCG risk was 64% good, 20% intermediate, and 16% poor. VTE occurred in 150 (13%) patients. RPLN >3.5 cm demonstrated highest discriminatory accuracy for VTE (AUC 0.632, P < .001) and was associated with significantly higher risk of VTE in univariable analysis (22% vs 8%, OR 3.0, P < .001) and multivariable analysis (OR 1.8, P = .02). Other significant risk factors included, Khorana score ≥3 (OR 2.6, P = .008) and VAD use (OR 2.7, P < .001).

Conclusions: Large RPLN and VAD use are independent risk factors for VTE in mGCT patients receiving chemotherapy. VAD use should be minimized in this population and thromboprophylaxis might be considered for large RPLN.
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http://dx.doi.org/10.1002/cam4.2674DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6943085PMC
January 2020

The Lung Immune Prognostic Index Discriminates Survival Outcomes in Patients with Solid Tumors Treated with Immune Checkpoint Inhibitors.

Cancers (Basel) 2019 Nov 2;11(11). Epub 2019 Nov 2.

Department of Oncology, University of Calgary, Calgary, Alta T2N 4N2, Canada.

Immune checkpoint inhibitors (ICI) have revolutionized the treatment landscape of several solid tumor types. However, as patient outcomes are heterogeneous, clinical tools to aid in prognostication are needed. The Lung Immune Prognostic Index (LIPI) correlates with outcomes in patients with non-small cell lung cancer (NSCLC) treated with ICI, but its applicability beyond NSCLC is poorly defined. We sought to determine whether LIPI is associated with overall survival (OS), progression-free survival (PFS) and objective response rate (ORR) in a pooled, real-world, retrospective cohort of patients with solid tumors treated with ICI. Of the total pooled cohort (N = 578), 47.2%, 38.2% and 14.5% of patients were stratified into good, intermediate and poor LIPI group, respectively. Median OS were 22.8 (95% CI 17.4-29.5), 7.8 (95% CI 6.6-9.6), and 2.5 months (95% CI 1.4-3.4) (p < 0.0001). Median PFS were 9.9 (95% CI 7.2-11.5), 3.6 (95% CI 2.7-4.3), and 1.4 months (95% CI 1.2-2.2) (p < 0.0001). ORR was also associated with LIPI group (p < 0.001). Intermediate and poor LIPI were independently prognostic of OS compared to good LIPI, with hazard ratios (HR) of 1.8 (95% CI 1.4-2.3, p < 0.001) and 3.6 (95% CI 2.5-5.1, p < 0.001), respectively. These data are the first to suggest that in a real-world setting, the prognostic value of LIPI may be tumor agnostic.
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http://dx.doi.org/10.3390/cancers11111713DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6896022PMC
November 2019

Asthma and Attendance in Urban Schools.

Prev Chronic Dis 2019 10 31;16:E148. Epub 2019 Oct 31.

Johns Hopkins School of Medicine, Department of Pediatrics, Baltimore, Maryland.

Introduction: Asthma is linked to student absenteeism, a risk factor for poor achievement and school dropout. Studies of asthma and absenteeism have common limitations, including relying on parent-reported asthma, which may be unreliable and prone to selection, and inadequately accounting for confounding health and social risks. Therefore, the rate of absenteeism attributable to asthma and the extent to which better asthma control would translate into better attendance remain unclear.

Methods: Participants were 1,194 students in 2 large urban US schools (1 elementary, 1 middle) in 2016-2018. Student asthma was assessed based on parent report on health forms, student-reported asthma-related emergency department/hospitalization or medication use, and school health center record of asthma. Multiple imputation was used to reduce selection from missing asthma reports. The relationship between asthma and school district-reported days absent was estimated using Poisson random intercept regression, accounting for health and demographic covariates.

Results: Parent-reported ever asthma (27%) was not associated with absenteeism in adjusted models. Student-reported asthma health care or medication use (16%) and school health center record of asthma (17%) were associated with higher absenteeism (incidence rate ratio [IRR], 1.16; 95% confidence interval [CI], 1.01-1.35 and IRR, 1.21; 95% CI, 1.09-1.34, respectively). Student-reported asthma and school health center record of asthma were associated with 1.9 and 1.5 absences per year, respectively.

Conclusion: Student-reported and school health center record of asthma explained 14% to 18% of student absenteeism, even after accounting for other health and social risks. When possible, student reports should supplement parent reports to ensure that students with asthma are identified and obtain access to care.
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http://dx.doi.org/10.5888/pcd16.190074DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6880919PMC
October 2019

Cluster Randomized Trial of a Pre/Interconception Health Intervention for Mothers in Pediatric Visits.

Acad Pediatr 2020 07 17;20(5):660-669. Epub 2019 Oct 17.

Department of Pediatrics, Johns Hopkins University School of Medicine, (KK Upadhya, KJ Psoter, KA Connor, KB Mistry, DJ Levy, and TL Cheng), Baltimore, Md; Department of Population, Family and Reproductive Health, Johns Hopkins Bloomberg School of Public Health, (TL Cheng), Baltimore, Md. Electronic address:

Objective: Recognizing that pediatric primary care focuses on family health and is an important location of contact for women of childbearing age, this project assessed the effectiveness of a pre/interconception women's health intervention delivered during pediatric primary care using a cluster randomized trial.

Methods: Pediatric clinicians were randomized to a screening and brief educational intervention group or usual care comparison group. Intervention group clinicians received training on pre/interconception care, including recommended counseling and referral resources for needs identified. Women presenting to primary care with their child ≤12 months were enrolled and assigned to the group corresponding to the assignment of their child's clinician. Mothers seen by clinicians in the intervention group completed a pre/interconception health screening tool and discussed results with their child's clinician during the visit. These mothers were compared to mothers seen by comparison group clinicians who did not receive the screening tool or clinician discussion. All enrolled mothers (Intervention and Comparison) received written preconception health information and a 90-day supply of multivitamins. Primary outcomes at 6 and 12 months post enrollment included contraception use, pregnancy, and access to and use of preventive health care. Secondary outcomes included daily folic acid supplementation, smoking, and substance use.

Results: A total of 415 women were enrolled and those who had at least 1 follow-up assessment were included in the analysis (n = 383). There was no significant effect of the intervention on contraceptive use, pregnancy incidence, or use of preventive care. Assignment to the intervention increased the odds of daily folic acid use (odds ratio 1.82, 95% confidence interval 1.25, 2.63) during follow-up. Intervention mothers were less likely to smoke at 6, but not 12 months.

Conclusions: Pediatric visits are an opportune location for addressing maternal health and this intervention demonstrated feasibility and improved outcomes for some but not all outcomes. Attention to maternal health needs in pediatric visits during infancy may be important for maintaining positive pre/interconception health behaviors.
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http://dx.doi.org/10.1016/j.acap.2019.10.003DOI Listing
July 2020

Association Between Maternal Exposure to Lead, Maternal Folate Status, and Intergenerational Risk of Childhood Overweight and Obesity.

JAMA Netw Open 2019 10 2;2(10):e1912343. Epub 2019 Oct 2.

Center on the Early Life Origins of Disease, Department of Population, Family, and Reproductive Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.

Importance: The first pediatric lead screening typically occurs at 1-year well-child care visits. However, data on the extent of maternal lead exposure and its long-term consequences for child health are lacking.

Objective: To investigate the associations between maternal red blood cell (RBC) lead levels and intergenerational risk of overweight or obesity (OWO) and whether adequate maternal folate status is associated with a reduction in OWO risk.

Design, Setting, And Participants: Prospective birth cohort study. The analysis was conducted from July 14, 2018, to August 2, 2019, at Johns Hopkins Bloomberg School of Public Health. This study included 1442 mother-child pairs recruited at birth from October 27, 2002, to October 10, 2013, and followed up prospectively at Boston Medical Center.

Main Outcomes And Measures: Child body mass index (BMI) z score, calculated according to US national reference data, and OWO, defined as BMI at or exceeding the 85th percentile for age and sex. Maternal RBC lead levels and plasma folate levels were measured in samples obtained 24 to 72 hours after delivery; child whole-blood lead level was obtained from the first pediatric lead screening.

Results: The mean (SD) age of mothers and children was 28.6 (6.5) years and 8.1 (3.1) years, respectively; 50.1% of children were boys. The median maternal RBC lead level and plasma folate level were 2.5 (interquartile range [IQR], 1.7-3.8) μg/dL and 32.2 (IQR, 22.1-44.4) nmol/L, respectively. The median child whole-blood lead level and child BMI z score were 1.4 (IQR, 1.4-2.0) μg/dL and 0.78 (IQR, -0.08 to 1.71), respectively. Maternal RBC lead level was associated with child OWO risk in a dose-response fashion, with an odds ratio (OR) of 1.65 (95% CI, 1.18-2.32) for high maternal RBC lead level (≥5.0 μg/dL) compared with low maternal RBC lead level (<2.0 μg/dL). Child OWO was highest among children of OWO mothers with high RBC lead levels (adjusted OR, 4.24; 95% CI, 2.64-6.82) compared with children of non-OWO mothers with low RBC lead levels. Children of OWO mothers with high RBC lead levels had 41% lower OWO risk (OR, 0.59; 95% CI, 0.36-0.95; P = .03) if their mothers had adequate plasma folate levels (≥20.4 nmol/L) compared with their counterparts.

Conclusions And Relevance: In this sample of a US urban population, findings suggest that maternal elevated lead exposure was associated with increased risk of intergenerational OWO independent of postnatal blood lead levels. Adequate maternal folate status appeared to be associated with lower OWO risk. If confirmed by additional studies, these findings have implications for prenatal lead screening and management to minimize adverse health consequences on children.
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http://dx.doi.org/10.1001/jamanetworkopen.2019.12343DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6777254PMC
October 2019

The Uniqueness and Importance of Children in Addressing Health Disparities Across the Life Course: Implications for Research.

Epidemiology 2019 11;30 Suppl 2:S60-S64

From the Department of Pediatrics, Johns Hopkins School of Medicine, Baltimore, MD.

As the Eunice Kennedy Shriver National Institute of Child Health and Human Development's Division of Intramural Population Health Research celebrates its 50th Anniversary, it is appropriate to recognize great achievements in reducing child morbidity and mortality and increasing life expectancy. Unfortunately large racial/ethnic and socioeconomic health and healthcare disparities persist. This commentary suggests a framework to clarify the research and interventions needed to eliminate health disparities starting early in the life course.
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http://dx.doi.org/10.1097/EDE.0000000000001069DOI Listing
November 2019

Pathogen invasion history elucidates contemporary host pathogen dynamics.

PLoS One 2019 19;14(9):e0219981. Epub 2019 Sep 19.

Department of Ecology Evolution and Marine Biology, University of California Santa Barbara, Santa Barbara, California, United States of America.

Amphibians, the most threatened group of vertebrates, are seen as indicators of the sixth mass extinction on earth. Thousands of species are threatened with extinction and many have been affected by an emerging infectious disease, chytridiomycosis, caused by the fungal pathogen, Batrachochytrium dendrobatidis (Bd). However, amphibians exhibit different responses to the pathogen, such as survival and population persistence with infection, or mortality of individuals and complete population collapse after pathogen invasion. Multiple factors can affect host pathogen dynamics, yet few studies have provided a temporal view that encompasses both the epizootic phase (i.e. pathogen invasion and host collapse), and the transition to a more stable co-existence (i.e. recovery of infected host populations). In the Sierra Nevada mountains of California, USA, conspecific populations of frogs currently exhibit dramatically different host/ Bd-pathogen dynamics. To provide a temporal context by which present day dynamics may be better understood, we use a Bd qPCR assay to test 1165 amphibian specimens collected between 1900 and 2005. Our historical analyses reveal a pattern of pathogen invasion and eventual spread across the Sierra Nevada over the last century. Although we found a small number of Bd-infections prior to 1970, these showed no sign of spread or increase in infection prevalence over multiple decades. After the late 1970s, when mass die offs were first noted, our data show Bd as much more prevalent and more spatially spread out, suggesting epizootic spread. However, across the ~400km2 area, we found no evidence of a wave-like pattern, but instead discovered multiple, nearly-simultaneous invasions within regions. We found that Bd invaded and spread in the central Sierra Nevada (Yosemite National Park area) about four decades before it invaded and spread in the southern Sierra Nevada (Sequoia and Kings Canyon National Parks area), and suggest that the temporal pattern of pathogen invasion may help explain divergent contemporary host pathogen dynamics.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0219981PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6752790PMC
March 2020

Global Child Health: beyond surviving to thriving.

Pediatr Res 2019 12;86(6):683-684

Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

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http://dx.doi.org/10.1038/s41390-019-0574-6DOI Listing
December 2019

Inter-generational link of obesity in term and preterm births: role of maternal plasma acylcarnitines.

Int J Obes (Lond) 2019 10 22;43(10):1967-1977. Epub 2019 Jul 22.

Department of Population, Family and Reproductive Health, Center on the Early Life Origins of Disease, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.

Background/objectives: Acylcarnitines, intermediates of fatty acid oxidation, are known to be involved in obesity and insulin resistance. Since maternal prepregnancy overweight or obesity (OWO) is a recognized major risk factor for offspring OWO, we hypothesized that maternal plasma acylcarnitines may play a role in inter-generational OWO.

Subjects/methods: This study included 1402 mother-child pairs (1043 term, 359 preterm) recruited at birth from 1998-2013 and followed prospectively up to age 18 years at the Boston Medical Center. The primary outcomes were child OWO defined as BMI ≥ 85th percentile for age and sex. The primary exposures were maternal prepregnancy OWO defined as BMI ≥ 25 kg/m and maternal acylcarnitine levels measured in plasma samples collected soon after delivery using liquid chromatography-tandem mass spectrometry (LC-MS) in a targeted manner.

Results: Approximately 40% of the children in this study were OWO by age 5. Maternal OWO had a significant association with childhood OWO, both in term and preterm births. β-hydroxybutyryl-carnitine (C4-OH) levels were significantly and positively associated with child OWO among term births after adjustment for potential confounders and multiple-comparisons. Children born to OWO mothers in the top tertile C4-OH levels were at the highest risk of OWO: OR = 3.78 (95%CI: 2.47, 5.79) as compared with those born to non-OWO mothers in the lowest tertile (P for interaction of maternal OWO and C4-OH = 0.035). In a four-way decomposition of mediation/interaction analysis, we estimated that C4-OH levels explained about 27% (se = 0.08) of inter-generational OWO risk (P = 0.001). In contrast, these associations were not observed in preterm births.

Conclusions: In this U.S. urban low-income birth cohort, we provide further evidence of the inter-generational link of OWO and reveal the differential role of C4-OH in explaining the inter-generational obesity between term and preterm births. Further investigations are warranted to better understand and prevent the inter-generational transmission of OWO.
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http://dx.doi.org/10.1038/s41366-019-0417-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6900290PMC
October 2019