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  1. Article ; Online: Modelling organophosphate intoxication in C. elegans highlights nicotinic acetylcholine receptor determinants that mitigate poisoning.

    Izquierdo, Patricia G / Charvet, Claude L / Neveu, Cedric / Green, A Christopher / Tattersall, John E H / Holden-Dye, Lindy / O'Connor, Vincent

    PloS one

    2023  Volume 18, Issue 4, Page(s) e0284786

    Abstract: ... stimulation of acetylcholine receptors. Here, we use the organophosphate paraoxon-ethyl to treat C. elegans ...

    Abstract Organophosphate intoxication via acetylcholinesterase inhibition executes neurotoxicity via hyper stimulation of acetylcholine receptors. Here, we use the organophosphate paraoxon-ethyl to treat C. elegans and use its impact on pharyngeal pumping as a bio-assay to model poisoning through these neurotoxins. This assay provides a tractable measure of acetylcholine receptor mediated contraction of body wall muscle. Investigation of the time dependence of organophosphate treatment and the genetic determinants of the drug-induced inhibition of pumping highlight mitigating modulation of the effects of paraoxon-ethyl. We identified mutants that reduce acetylcholine receptor function protect against the consequence of intoxication by organophosphates. Data suggests that reorganization of cholinergic signalling is associated with organophosphate poisoning. This reinforces the under investigated potential of using therapeutic approaches which target a modulation of nicotinic acetylcholine receptor function to treat the poisoning effects of this important class of neurotoxins.
    MeSH term(s) Animals ; Organophosphate Poisoning/drug therapy ; Paraoxon/therapeutic use ; Paraoxon/toxicity ; Cholinesterase Inhibitors/therapeutic use ; Caenorhabditis elegans/genetics ; Caenorhabditis elegans/metabolism ; Acetylcholinesterase/metabolism ; Receptors, Nicotinic/genetics ; Neurotoxins ; Organophosphates/toxicity ; Organophosphates/therapeutic use
    Chemical Substances ethylparaoxon ; Paraoxon (Q9CX8P80JW) ; Cholinesterase Inhibitors ; Acetylcholinesterase (EC 3.1.1.7) ; Receptors, Nicotinic ; Neurotoxins ; Organophosphates
    Language English
    Publishing date 2023-04-21
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2267670-3
    ISSN 1932-6203 ; 1932-6203
    ISSN (online) 1932-6203
    ISSN 1932-6203
    DOI 10.1371/journal.pone.0284786
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  2. Article ; Online: Human INHBB Gene Variant (c.1079T>C:p.Met360Thr) Alters Testis Germ Cell Content, but Does Not Impact Fertility in Mice.

    Houston, Brendan J / O'Connor, Anne E / Wang, Degang / Goodchild, Georgia / Merriner, D Jo / Luan, Haitong / Conrad, Don F / Nagirnaja, Liina / Aston, Kenneth I / Kliesch, Sabine / Wyrwoll, Margot J / Friedrich, Corinna / Tüttelmann, Frank / Harrison, Craig / O'Bryan, Moira K / Walton, Kelly

    Endocrinology

    2022  Volume 163, Issue 3

    Abstract: ... Previously, we identified a homozygous genetic variant (c.1079T>C:p.Met360Thr) arising ... an additional INHBB variant (c.314C>T: p.Thr105Met) found in another infertile man on inhibin B and activin B ...

    Abstract Testicular-derived inhibin B (α/β B dimers) acts in an endocrine manner to suppress pituitary production of follicle-stimulating hormone (FSH), by blocking the actions of activins (β A/B/β A/B dimers). Previously, we identified a homozygous genetic variant (c.1079T>C:p.Met360Thr) arising from uniparental disomy of chromosome 2 in the INHBB gene (β B-subunit of inhibin B and activin B) in a man suffering from infertility (azoospermia). In this study, we aimed to test the causality of the p.Met360Thr variant in INHBB and testis function. Here, we used CRISPR/Cas9 technology to generate InhbbM364T/M364T mice, where mouse INHBB p.Met364 corresponds with human p.Met360. Surprisingly, we found that the testes of male InhbbM364T/M364T mutant mice were significantly larger compared with those of aged-matched wildtype littermates at 12 and 24 weeks of age. This was attributed to a significant increase in Sertoli cell and round spermatid number and, consequently, seminiferous tubule area in InhbbM364T/M364T males compared to wildtype males. Despite this testis phenotype, male InhbbM364T/M364T mutant mice retained normal fertility. Serum hormone analyses, however, indicated that the InhbbM364T variant resulted in reduced circulating levels of activin B but did not affect FSH production. We also examined the effect of this p.Met360Thr and an additional INHBB variant (c.314C>T: p.Thr105Met) found in another infertile man on inhibin B and activin B in vitro biosynthesis. We found that both INHBB variants resulted in a significant disruption to activin B in vitro biosynthesis. Together, this analysis supports that INHBB variants that limit activin B production have consequences for testis composition in males.
    MeSH term(s) Activins/biosynthesis ; Activins/genetics ; Animals ; Azoospermia/genetics ; CRISPR-Associated Protein 9 ; Follicle Stimulating Hormone/metabolism ; Humans ; Infertility, Male/genetics ; Infertility, Male/physiopathology ; Inhibin-beta Subunits/genetics ; Inhibin-beta Subunits/physiology ; Inhibins/biosynthesis ; Inhibins/genetics ; Male ; Mice ; Mice, Inbred C57BL ; Mutation ; Sertoli Cells ; Sperm Count ; Spermatogenesis/genetics ; Spermatogonia ; Testis/chemistry ; Testis/cytology ; Testis/physiopathology
    Chemical Substances INHBB protein, human ; Inhbb protein, mouse ; activin B ; inhibin B ; Activins (104625-48-1) ; Inhibins (57285-09-3) ; Follicle Stimulating Hormone (9002-68-0) ; Inhibin-beta Subunits (93443-12-0) ; CRISPR-Associated Protein 9 (EC 3.1.-)
    Language English
    Publishing date 2022-01-12
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 427856-2
    ISSN 1945-7170 ; 0013-7227
    ISSN (online) 1945-7170
    ISSN 0013-7227
    DOI 10.1210/endocr/bqab269
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  3. Article ; Online: PDGFRβ Signaling Cooperates with β-Catenin to Modulate c-Abl and Biologic Behavior of Desmoid-Type Fibromatosis.

    Hu, Jia / Hameed, Meera R / Agaram, Narasimhan P / Whiting, Karissa A / Qin, Li-Xuan / Villano, Anthony M / O'Connor, Rachael B / Rozenberg, Julian M / Cohen, Sonia / Prendergast, Katherine / Kryeziu, Sara / White, Richard L / Posner, Mitchell C / Socci, Nicholas D / Gounder, Mrinal M / Singer, Samuel / Crago, Aimee M

    Clinical cancer research : an official journal of the American Association for Cancer Research

    2023  Volume 30, Issue 2, Page(s) 450–461

    Abstract: ... reduced HIF1α protein expression and c-Abl activity while inhibiting PDGFRβ signaling in desmoid cells ... Conversely, c-Abl activity and desmoid cell proliferation were positively regulated by PDGF-BB. Reduction ... in PDGFRβ and c-Abl phosphorylation was commonly observed in biopsy samples from patients after treatment ...

    Abstract Purpose: This study sought to identify β-catenin targets that regulate desmoid oncogenesis and determine whether external signaling pathways, particularly those inhibited by sorafenib (e.g., PDGFRβ), affect these targets to alter natural history or treatment response in patients.
    Experimental design: In vitro experiments utilized primary desmoid cell lines to examine regulation of β-catenin targets. Relevance of results was assessed in vivo using Alliance trial A091105 correlative biopsies.
    Results: CTNNB1 knockdown inhibited hypoxia-regulated gene expression in vitro and reduced levels of HIF1α protein. ChIP-seq identified ABL1 as a β-catenin transcriptional target that modulated HIF1α and desmoid cell proliferation. Abrogation of either CTNNB1 or HIF1A inhibited desmoid cell-induced VEGFR2 phosphorylation and tube formation in endothelial cell co-cultures. Sorafenib inhibited this activity directly but also reduced HIF1α protein expression and c-Abl activity while inhibiting PDGFRβ signaling in desmoid cells. Conversely, c-Abl activity and desmoid cell proliferation were positively regulated by PDGF-BB. Reduction in PDGFRβ and c-Abl phosphorylation was commonly observed in biopsy samples from patients after treatment with sorafenib; markers of PDGFRβ/c-Abl pathway activation in baseline samples were associated with tumor progression in patients on the placebo arm and response to sorafenib in patients receiving treatment.
    Conclusions: The β-catenin transcriptional target ABL1 is necessary for proliferation and maintenance of HIF1α in desmoid cells. Regulation of c-Abl activity by PDGF signaling and targeted therapies modulates desmoid cell proliferation, thereby suggesting a reason for variable biologic behavior between tumors, a mechanism for sorafenib activity in desmoids, and markers predictive of outcome in patients.
    MeSH term(s) Humans ; Fibromatosis, Aggressive/drug therapy ; Fibromatosis, Aggressive/genetics ; beta Catenin/genetics ; beta Catenin/metabolism ; Sorafenib/pharmacology ; Signal Transduction ; Biological Products
    Chemical Substances beta Catenin ; Sorafenib (9ZOQ3TZI87) ; Biological Products
    Language English
    Publishing date 2023-11-07
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 1225457-5
    ISSN 1557-3265 ; 1078-0432
    ISSN (online) 1557-3265
    ISSN 1078-0432
    DOI 10.1158/1078-0432.CCR-23-2313
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  4. Article ; Online: Hypertension induces glomerulosclerosis in phospholipase C-ε1 deficiency.

    Atchison, Douglas K / O'Connor, Christopher L / Menon, Rajasree / Otto, Edgar A / Ganesh, Santhi K / Wiggins, Roger C / Smrcka, Alan V / Bitzer, Markus

    American journal of physiology. Renal physiology

    2020  Volume 318, Issue 5, Page(s) F1177–F1187

    Abstract: Loss-of-function mutations in phospholipase C-ε1 (PLCE1) have been detected in patients ...

    Abstract Loss-of-function mutations in phospholipase C-ε1 (PLCE1) have been detected in patients with nephrotic syndrome, but other family members with the same mutation were asymptomatic, suggesting additional stressor are required to cause the full phenotype. Consistent with these observations, we determined that global
    MeSH term(s) Albuminuria/enzymology ; Albuminuria/genetics ; Albuminuria/physiopathology ; Animals ; Blood Pressure ; Desoxycorticosterone Acetate ; Disease Models, Animal ; Female ; Glomerulonephritis/enzymology ; Glomerulonephritis/genetics ; Glomerulonephritis/pathology ; Glomerulonephritis/physiopathology ; Hypertension/enzymology ; Hypertension/genetics ; Hypertension/physiopathology ; Kidney Glomerulus/enzymology ; Kidney Glomerulus/pathology ; Kidney Glomerulus/physiopathology ; Male ; Mice, Inbred C57BL ; Mice, Knockout ; Nephrectomy ; Phosphoinositide Phospholipase C/deficiency ; Phosphoinositide Phospholipase C/genetics ; Sodium Chloride, Dietary
    Chemical Substances Sodium Chloride, Dietary ; Desoxycorticosterone Acetate (6E0A168OB8) ; Phosphoinositide Phospholipase C (EC 3.1.4.11) ; phospholipase C epsilon (EC 3.1.4.11)
    Language English
    Publishing date 2020-03-30
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 603837-2
    ISSN 1522-1466 ; 0363-6127
    ISSN (online) 1522-1466
    ISSN 0363-6127
    DOI 10.1152/ajprenal.00541.2019
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  5. Article: A mixed methods study of Attendance and Treatment Rates among Patients with Hepatitis C.

    Nic An Ríogh, E / McCombe, G / Connolly, S P / Fawsitt, R / McHugh, T / O'Connor, E / Stewart, S / Swan, D / Tinago, W / Cullen, W / Lambert, J S

    Irish medical journal

    2023  Volume 116, Issue 2, Page(s) 742

    MeSH term(s) Humans ; Hepatitis C/drug therapy ; Hepatitis C/epidemiology ; Hepacivirus ; Patients
    Language English
    Publishing date 2023-02-23
    Publishing country Ireland
    Document type Journal Article
    ZDB-ID 193134-9
    ISSN 0332-3102 ; 0021-129X
    ISSN 0332-3102 ; 0021-129X
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  6. Article ; Online: Hepatitis C Virus Cascade of Care Among Perinatal Patients in Maine Diagnosed With Opioid Use Disorder, 2015-2020.

    Pfeiffer, Mariah / O'Connor, Alane / Zimmerman, Caroline / Thakarar, Kinna / Ahrens, Katherine

    Journal of addiction medicine

    2022  Volume 17, Issue 3, Page(s) 286–293

    Abstract: ... address gaps in care for perinatal patients in receiving appropriate hepatitis C virus (HCV) testing and ...

    Abstract Objective: This is a quality improvement project to determine the best process to identify and address gaps in care for perinatal patients in receiving appropriate hepatitis C virus (HCV) testing and treatment across the largest health system in Maine.
    Study design: We reviewed electronic medical record data between October 1, 2015, and February 1, 2020, to investigate rates of HCV testing and treatment among 916 perinatal patients with opioid use disorder across 8 hospitals using a "cascade of care" framework, a model used previously to identify gaps in care and treatment of chronic diseases.
    Main outcome measure: We examined HCV testing and treatment rates along the cascade of care and patient characteristics associated with HCV antibody testing and treatment, separately, using log binomial regression models. Models were adjusted for age, residential distance to medical center, psychiatric diagnosis, and opioid agonist therapy at delivery.
    Results: Of pregnant patients eligible for screening, 64% (582/916) received HCV antibody testing. Of 136 patients with active HCV infection, 32% (n = 43) received a referral for treatment, 21% (n = 28) were treated, and 13% (n = 18) achieved sustained virologic response. In the adjusted regression models, only opioid agonist therapy was associated with HCV antibody testing (adjusted risk ratio, 1.31; 95% confidence interval, 1.18-1.46), and no factors were significantly associated with receipt of treatment among HCV viremic patients.
    Conclusion: Low referral and treatment rates signify the need for quality improvement interventions to improve coordination of care between multiple disciplines and practice settings to increase access to HCV treatment.
    MeSH term(s) Pregnancy ; Female ; Humans ; Hepacivirus ; Analgesics, Opioid/therapeutic use ; Maine/epidemiology ; Hepatitis C/diagnosis ; Hepatitis C/drug therapy ; Hepatitis C/epidemiology ; Opioid-Related Disorders/drug therapy ; Opioid-Related Disorders/complications ; Antiviral Agents/therapeutic use ; Hepatitis C, Chronic/drug therapy
    Chemical Substances Analgesics, Opioid ; Antiviral Agents
    Language English
    Publishing date 2022-10-27
    Publishing country Netherlands
    Document type Review ; Journal Article
    ISSN 1935-3227
    ISSN (online) 1935-3227
    DOI 10.1097/ADM.0000000000001098
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  7. Article ; Online: The DA VINCI study: is Ireland achieving ESC/EAS guideline-directed LDL-C goals?

    Offiah, Gregory / O'Connor, Cormac / Kennedy, Cormac / Gallagher, Joe / O'Connor, Patricia / McAdam, Brendan / Ray, Kausik K / Schoonen, Marieke / Maher, Vincent

    Irish journal of medical science

    2022  Volume 192, Issue 3, Page(s) 1077–1084

    Abstract: ... low-density lipoprotein cholesterol (LDL-C) goals recommended by the European Society of Cardiology (ESC)/European Atherosclerosis ... 2016 and 2019 ESC/EAS LDL-C goals. This subgroup analysis aimed to evaluate LDL-C goal attainment ... 60% of patients achieved their 2016 ESC/EAC LDL-C goals while less than half the patients achieved ...

    Abstract Background: The EU-wide, cross-sectional observational study of lipid-lowering therapy (LLT) use in secondary and primary care (DA VINCI) assessed the proportion of patients achieving low-density lipoprotein cholesterol (LDL-C) goals recommended by the European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) guidelines and provided an insight into regional use of LLT in Europe, including Ireland.
    Aims: This analysis focuses on data from patients in Ireland who participated in the DA VINCI study.
    Methods: The DA VINCI study enrolled patients receiving LLT at primary and secondary care sites across 18 European countries between June 2017 and November 2018. The study assessed the achievement of risk-based 2016 and 2019 ESC/EAS LDL-C goals. This subgroup analysis aimed to evaluate LDL-C goal attainment in an Irish cohort of primary and secondary care patients.
    Results: In total, 198 patients from Ireland were enrolled from three primary care and three secondary care centres. Most patients were White and male, and were receiving moderate- or high-intensity statin therapy (most frequently atorvastatin or rosuvastatin). Few patients (< 10%) were receiving combination therapy of statin and ezetimibe. Approximately 60% of patients achieved their 2016 ESC/EAC LDL-C goals while less than half the patients achieved their 2019 ESC/EAS goals. Approximately half of secondary prevention patients achieved their 2016 ESC/EAS goals and only 20% of secondary prevention patients achieved their 2019 ESC/EAS goals.
    Conclusions: These results highlight the disparity between dyslipidaemia management in clinical practice in Ireland and guideline recommendations.
    Trial registration: ENCePP; EU PAS 22,075; date registered 06 February 2018.
    MeSH term(s) Humans ; Male ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use ; Cholesterol, LDL ; Goals ; Ireland ; Cross-Sectional Studies ; Cardiology ; Atherosclerosis/complications ; Dyslipidemias/chemically induced ; Dyslipidemias/complications ; Dyslipidemias/drug therapy ; Treatment Outcome
    Chemical Substances Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Cholesterol, LDL
    Language English
    Publishing date 2022-07-01
    Publishing country Ireland
    Document type Observational Study ; Journal Article
    ZDB-ID 390895-1
    ISSN 1863-4362 ; 0021-1265
    ISSN (online) 1863-4362
    ISSN 0021-1265
    DOI 10.1007/s11845-022-03050-6
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    Zs.B 323: Show issues Location:
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  8. Article ; Online: Survivor engagement: Experience with an advocacy-based model in Washington, D.C.

    O Connor, Seini / Barron, Andrea / Byimana, Léonce / Isley, Jennifer / Patel, Sheetal / Dhital, Yadhu / Bazaz, Nouf

    Torture : quarterly journal on rehabilitation of torture victims and prevention of torture

    2023  Volume 33, Issue 2, Page(s) 85–101

    Abstract: ... in Washington D.C. Quantitative and qualitative data was collected to inform internal service provision and ...

    Abstract Introduction: As an IRCT member organization supporting survivors of torture, the Torture Abolition and Survivor Support Coalition (TASSC) International places survivor engagement at the core of their work, aiming to provide safe and inclusive spaces for survivors to speak out and take meaningful action to prevent torture. This article describes TASSC's model for engaging survivors in advocacy and presents evidence on the personal impacts such engagement can have.
    Method: Each year from 2016-2019, TASSC administered a simple survey with questions for survivors to complete after their annual "Advocacy Day" in Washington D.C. Quantitative and qualitative data was collected to inform internal service provision and the design of future events.
    Results: Across the four years a total of 140 survivors and compatriot human rights advocates participated in the annual Advocacy Day, and a majority completed the surveys. In their survey responses, survivors agreed they had many positive thoughts and feelings after advocacy. Their reported positive experiences included a sense of being listened to and heard by an understanding and responsive audience, the power of feeling part of a group that was speaking out on behalf of themselves and others, and a sense of motivation and hopefulness for the future.
    Discussion: Although undertaken primarily to inform internal processes, TASSC's surveys with survivors who engaged in advocacy shed light on the potential value of well-designed advocacy experiences. Consistent with past research, survivors reported strong motivations around and compelling benefits from participating, despite the challenges that the deeply personal nature of their engagement could present. This feedback suggests TASSC has a strong model that could be replicated elsewhere, but it would be beneficial to further investigate the experiences of survivors engaging in advocacy in other country settings.
    MeSH term(s) Humans ; District of Columbia ; Washington ; Auditory Perception ; Data Accuracy ; Survivors
    Language English
    Publishing date 2023-08-14
    Publishing country Denmark
    Document type Journal Article
    ZDB-ID 1170269-2
    ISSN 1997-3322 ; 1018-8185 ; 0904-1982
    ISSN (online) 1997-3322
    ISSN 1018-8185 ; 0904-1982
    DOI 10.7146/torture.v33i2.135716
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  9. Article ; Online: Missed Opportunities for HIV and Hepatitis C Screening Among Emergency Department Patients With Untreated Opioid Use Disorder.

    Lyons, Michael S / Chawarski, Marek C / Rothman, Richard / Whiteside, Lauren / Cowan, Ethan / Richardson, Lynne D / Hawk, Kathryn / Tsui, Judith I / Schwartz, Robert P / O'Connor, Patrick / D'Onofrio, Gail / Fiellin, David A / Edelman, E Jennifer

    Journal of addiction medicine

    2022  Volume 17, Issue 2, Page(s) 210–214

    Abstract: Objective: We assessed the frequency of emergency department (ED) HIV and hepatitis C (HCV ...

    Abstract Objective: We assessed the frequency of emergency department (ED) HIV and hepatitis C (HCV) screening in a high-risk cohort of ED patients with untreated opioid use disorder (OUD).
    Methods: This analysis used data from a prospective, observational study of English-speaking adults with untreated OUD enrolled from April 2017 to December 2018 in 4 urban, academic EDs. Two cohorts were defined for this analysis by self-reported negative/unknown status for HIV (cohort 1) and HCV (cohort 2). Sites featured structured screening programs throughout the entire enrollment period for HIV and during at least part of the enrollment period for HCV. We calculated the proportion tested for HIV and HCV during the study enrollment ED visit.
    Results: Among 394 evaluated ED patients, 328 of 394 (83.2%) were not tested for HIV or HCV and 244 of 393 (62.1%) lacked a usual medical care provider. In cohort 1, 375 reported negative or unknown HIV status; 59/375 (15.7%) overall and 33/218 (15.1%) of those reporting recent injection drug use were tested for HIV. In cohort 2, 231 reported negative of unknown HCV status; 22/231 (9.5%) overall and 9/98 (9.2%) of those reporting recent injection drug use were tested for HCV. The proportion tested by the ED ranged from 3% to 25% for HIV and 4% to 32% for HCV across study sites.
    Conclusions: Emergency department HIV and HCV screening remains infrequent among patients with untreated OUD, including those who inject drugs, even in EDs committed to screening. Targeted HIV/HCV screening should be considered as an adjunct strategy until the ideal of universal screening is more fully achieved.
    MeSH term(s) Adult ; Humans ; Prospective Studies ; Hepatitis C/diagnosis ; Hepatitis C/epidemiology ; Emergency Service, Hospital ; Hepacivirus ; Opioid-Related Disorders/diagnosis ; Opioid-Related Disorders/epidemiology ; HIV Infections/diagnosis ; HIV Infections/epidemiology
    Language English
    Publishing date 2022-09-27
    Publishing country Netherlands
    Document type Observational Study ; Journal Article ; Research Support, N.I.H., Extramural
    ISSN 1935-3227
    ISSN (online) 1935-3227
    DOI 10.1097/ADM.0000000000001074
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  10. Article ; Online: The Association of Prenatal C-Reactive Protein Levels With Childhood Asthma and Atopy.

    Chen, Yih-Chieh S / Lee-Sarwar, Kathleen A / Mirzakhani, Hooman / O'Connor, George T / Bacharier, Leonard B / Zeiger, Robert S / Knihtilä, Hanna M / Jha, Anjali / Kelly, Rachel S / Laranjo, Nancy / Fichorova, Raina N / Luu, Ngan / Weiss, Scott T / Litonjua, Augusto A

    The journal of allergy and clinical immunology. In practice

    2022  Volume 10, Issue 12, Page(s) 3213–3219.e11

    Abstract: ... C-reactive protein (CRP), with childhood asthma, eczema, and allergic rhinitis.: Methods: A total ...

    Abstract Background: The pathogenesis of childhood asthma is complex, and determinants of risk may begin in utero.
    Objective: To describe the association of systemic prenatal inflammation, measured by plasma C-reactive protein (CRP), with childhood asthma, eczema, and allergic rhinitis.
    Methods: A total of 522 maternal-offspring pairs from the Vitamin D Antenatal Asthma Reduction Trial were included. Prenatal plasma CRP level was measured between 10 and 18 weeks of gestation and between 32 and 38 weeks of gestation. Offspring asthma, eczema, and allergic rhinitis were assessed quarterly between birth and age 6 years. We performed mediation analyses of prenatal CRP on the association between several maternal characteristics and offspring asthma.
    Results: Elevated early and late prenatal CRP and an increase in CRP from early to late pregnancy were associated with asthma by age 6 years (early: adjusted odds ratio [aOR], 1.76, 95% CI, 1.12-2.82, P = .02; late: aOR, 2.45, 95% CI, 1.47-4.18, P < .001; CRP increase: aOR, 2.06, 95% CI, 1.26-3.39, P < .004). Prenatal CRP and childhood asthma associations were strengthened among offspring with atopic asthma (early: aOR, 3.78, 95% CI, 1.49-10.64, P = .008; late: aOR, 4.84, 95% CI, 1.68-15.50, P = .005; CRP increase: aOR, 3.01, 95% CI, 1.06-9.16, P = .04). Early and late prenatal CRP mediated 96% and 86% of the association between maternal prepregnancy body mass index and offspring asthma, respectively.
    Conclusions: Higher prenatal CRP and an increase in CRP from early to late pregnancy are associated with childhood asthma. Systemic inflammation during pregnancy associated with modifiable maternal characteristics may be an important determinant of childhood asthma risk.
    MeSH term(s) Child ; Female ; Humans ; Pregnancy ; Asthma/complications ; C-Reactive Protein/metabolism ; Eczema/etiology ; Hypersensitivity, Immediate/etiology ; Inflammation ; Prenatal Exposure Delayed Effects/epidemiology ; Rhinitis, Allergic/complications ; Vitamins
    Chemical Substances C-Reactive Protein (9007-41-4) ; Vitamins
    Language English
    Publishing date 2022-09-13
    Publishing country United States
    Document type Clinical Trial ; Journal Article
    ZDB-ID 2843237-X
    ISSN 2213-2201 ; 2213-2198
    ISSN (online) 2213-2201
    ISSN 2213-2198
    DOI 10.1016/j.jaip.2022.08.044
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