14 results on '"Baldacci, S"'
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2. Single breath nitrogen test as predictor of lung function decline and COPD over an 8-year follow-up
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Pistelli, F., Sherrill, D.L., Di Pede, F., Baldacci, S., Simoni, M., Maio, S., Carrozzi, L., and Viegi, G.
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- 2024
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3. Algorithme thérapeutique des cancers bronchiques non à petites cellules étendus avec mutation de l’EGFR
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Cadranel, J., Fallet, V., Baldacci, S., Duruisseaux, M., and Cortot, A.
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Les mutations de l’EGFR restent aujourd’hui le mécanisme d’addiction oncogénique ciblable le plus fréquemment observé au cours des cancers bronchiques non à petites cellules (CBNPC) étendus, représentant 12 % des adénocarcinomes et 44 % des CBNPC des non-fumeurs, en France. Les mutations « communes » de l’EGFR – délétions de l’exon 19 et mutation L858R de l’exon 21, sont observées dans 89 % des cas. L’utilisation des nouvelles techniques de biologie moléculaire nous confronte à l’identification de mutations « rares» de l’EGFR – en particulier les insertions dans l’exon 20, mais aussi à la constatation d’une hétérogénéité moléculaire au diagnostic et durant le suivi. Cette hétérogénéité d’une part, explique en partie les variations d’efficacité observées des inhibiteurs de tyrosine kinase de l’EGFR (ITK-EGFR) et d’autre part, conduit à l’émergence de clones résistants. L’osimertinib est le standard de 1religne thérapeutique. Cependant, la place de la chimiothérapie associée ou l’émergence de l’amivantamab (anticorps bispécifique EGFR et MET) pourraient modifier l’organisation des séquences thérapeutiques, afin d’obtenir une amélioration de la survie globale, mais au dépend d’une augmentation des toxicités et de ce fait d’un risque de détérioration de la qualité de vie. L’enjeu actuel est de déterminer les populations de patients pouvant justifier d’une combinaison thérapeutique dès la 1religne de traitement.
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- 2024
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4. Oncogenèse pulmonaire : de l’altération moléculaire au cancer
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Baldacci, S., Blons, H., Mascaux, C., and Leroy, K.
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Comme pour tout cancer, les lésions tumorales pulmonaires résultent de l’acquisition d’un ensemble de mutations dites « driver » (pilote), associées à des modifications épigénétiques et à la mise en place d’un micro-environnement tumoral stromal, vasculaire et immunitaire permissif. Les mécanismes à l’origine de l’oncogenèse pulmonaire ont bénéficié des études génomiques récentes, comme celles de la cohorte TRACERx. Certaines mutations sont associées à une dépendance oncogénique pouvant être spécifiquement ciblée. L’évolution clonale et sous-clonale des cellules tumorales conditionne l’histoire naturelle de la maladie, la survenue de récidives ou métastases à distance. Dans cette revue, nous nous focaliserons sur les processus touchant les cellules tumorales et nous n’aborderons pas les aspects liés au micro-environnement tumoral, même si celui-ci joue un rôle essentiel dans la survenue et l’évolution de la maladie. 1877-1203/© 2024 SPLF. Publié par Elsevier Masson SAS. Tous droits réservés.
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- 2024
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5. MA07.03 Systematic Engineering of TROP2 CAR T Cell Therapy to Overcome Resistance Pathways in EGFRmutant NSCLC
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Brea, E.J., Baldacci, S., Chakravarti, S., Mottram, A.P., Facchinetti, F., Ramasubramanian, A., Savage, N., Ngo, K., Vo, H.V., Leeper, B.A., Ivanova, E.V., Saldanha, A., Locquet, M.-A., Salamah, A., Stornante, C., Campisi, M., Mahadevan, N.R., Thai, T.C., Haggerty, T.J., Nie, C., Deng, C., Wang, X., Liu, L.L., Gokhale, P.C., Paweletz, C.P., Jänne, P.A., Barbie, D.A., and Smith, E.L.
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- 2024
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6. MA07.06 Eradicating Drug Tolerant Persisters (DTPs) In EGFR-Mutated Non Small Cell Lung Cancer (NSCLC) By Targeting TROP2
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Baldacci, S., Brea, E.J., Facchinetti, F., Malhotra, S., Tolstorukov, M., Booker, M., Li, Z., Chakravarti, S., Lococo, F., D’Agnelli, S., Gnetti, L., Leonetti, A., Feng, W.W., Tsai, J.A., Hartley, A.-V., Locquet, M.-A., Alessi, J.V., Awad, M.M., Lau, C., Saldanha, A., Chopade, P., Kivlehan, S., Ngo, K., Lizotte, P., Ivanova, E., Gokhale, P., Paweletz, C., Smith, E.L., Jänne, P.A., and Barbie, D.A.
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- 2024
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7. 1390P Clinical characteristics and treatment outcomes of patients with thoracic SMARCA4-deficient tumour
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Duparc, I., Castanet, E., Basse, C., Fallet, V., Baldacci, S., Demontrond, P., Oulkhouir, Y., Cousin, S., Arpin, D., Fournel, P., Leite Ferreira, D., Piton, N., and Guisier, F.
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- 2024
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8. Effects of traffic-related air and noise pollution exposure on allergic diseases in the elderly: an observational study.
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Tagliaferro S, Pirona F, Fasola S, Stanisci I, Sarno G, Baldacci S, Gariazzo C, Licitra G, Moro A, Silibello C, Stafoggia M, Viegi G, and Maio S
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- Humans, Middle Aged, Male, Female, Aged, Italy epidemiology, Adult, Adolescent, Young Adult, Air Pollution adverse effects, Traffic-Related Pollution adverse effects, Surveys and Questionnaires, Vehicle Emissions, Noise adverse effects, Rhinitis, Allergic epidemiology, Rhinitis, Allergic etiology, Hypersensitivity epidemiology, Hypersensitivity etiology, Logistic Models, Nitrogen Dioxide adverse effects, Nitrogen Dioxide analysis, Air Pollutants adverse effects, Noise, Transportation adverse effects, Environmental Exposure adverse effects
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Introduction: Traffic-related air and noise pollution are important public health issues. The aim of this study was to estimate their effects on allergic/respiratory outcomes in adult and elderly subjects., Materials and Methods: Six hundred and forty-five subjects living in Pisa (Tuscany, Italy) were investigated through a questionnaire on allergic/respiratory symptoms and diseases. Traffic-related air pollution and noise exposures were assessed at residential address by questionnaire, modelled annual mean NO
2 concentrations (1 km and 200 m resolution), and noise level over a 24-h period (Lden). Exposure effects were assessed through logistic regression models stratified by age group (18-64 years, ≥65 years), and adjusted for sex, educational level, occupational exposure, and smoking habits., Results: 63.6% of the subjects reported traffic exposure near home. Mean exposure levels were: 28.24 (±3.26 SD ) and 27.23 (±3.16 SD ) µg/m3 for NO2 at 200 m and 1 km of resolution, respectively; 57.79 dB(A) (±6.12 SD ) for Lden. Exposure to vehicular traffic (by questionnaire) and to high noise levels [Lden ≥ 60 dB(A)] were significantly associated with higher odds of allergic rhinitis (OR 2.01, 95%CI 1.09-3.70, and OR 1.99, 95%CI 1.18-3.36, respectively) and borderline with rhino-conjunctivitis (OR 2.20, 95%CI 0.95-5.10, and OR 1.76, 95%CI 0.91-3.42, respectively) only in the elderly. No significant result emerged for NO2 ., Conclusions: Our findings highlighted the need to better assess the effect of traffic-related exposure in the elderly, considering the increasing trend in the future global population's ageing.- Published
- 2024
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9. Health status of Italian children living close to cultivations sprayed with pesticides.
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Sarno G, Maio S, Baldacci S, Stanisci I, Angino A, Tagliaferro S, Silvi P, and Viegi G
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- Humans, Italy, Child, Female, Male, Adolescent, Surveys and Questionnaires, Risk Factors, Logistic Models, Agriculture, Respiratory Tract Diseases epidemiology, Respiratory Tract Diseases chemically induced, Pesticides adverse effects, Environmental Exposure adverse effects, Health Status
- Abstract
BACKGROUND Pesticides are used to control pests, but they are toxic and may severely harm children's health. We assessed health outcomes in Italian children living close to cultivations sprayed with pesticides.METHODS In 2011-2012, 2,367 schoolchildren (6-14 years) living in eight Italian cities participated in the Indoor-School observational study. Parents filled in a standardised questionnaire on children's health and related risk factors. Children were classified as exposed to pesticides if living close to cultivations sprayed with pesticides. The association between the last three months of respiratory, allergic or systemic symptoms and pesticide exposure was assessed by multinomial logistic regression models, accounting for host/environmental risk factors.RESULTS Overall, 14% of children were exposed to pesticides, with significant differences among geographical areas: 21.2% in Northern Italy, 11.6% in Central Italy, and 9.7% in Southern Italy. Pesticide exposure was significantly associated with having: 1) 'often': eye symptoms (OR 3.81, 95% CI 2.06-7.05), skin symptoms (OR 2.60, 95% CI 1.34-5.03), lower airway symptoms (OR 2.38, 95% CI 1.41-4.01), systemic symptoms (OR 1.56, 95% CI 0.96-2.53, borderline); 2) 'daily': upper airways symptoms (OR 2.25, 95% CI 1.25-4.07) and systemic symptoms (OR 2.76, 95% CI 1.43-5.34). .CONCLUSIONS Self-reported pesticide exposure was associated with respiratory, allergic or systemic symptoms in children. Public authorities should be aware of and intervene to mitigate this health risk.- Published
- 2024
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10. Activating Point Mutations in the MET Kinase Domain Represent a Unique Molecular Subset of Lung Cancer and Other Malignancies Targetable with MET Inhibitors.
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Pecci F, Nakazawa S, Ricciuti B, Harada G, Lee JK, Alessi JV, Barrichello A, Vaz VR, Lamberti G, Di Federico A, Gandhi MM, Gazgalis D, Feng WW, Jiang J, Baldacci S, Locquet MA, Gottlieb FH, Chen MF, Lee E, Haradon D, Smokovich A, Voligny E, Nguyen T, Goel VK, Zimmerman Z, Atwal S, Wang X, Bahcall M, Heist RS, Iqbal S, Gandhi N, Elliott A, Vanderwalde AM, Ma PC, Halmos B, Liu SV, Che J, Schrock AB, Drilon A, Jänne PA, and Awad MM
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- Humans, Animals, Mice, Cell Line, Tumor, Proto-Oncogene Proteins c-met genetics, Proto-Oncogene Proteins c-met antagonists & inhibitors, Lung Neoplasms genetics, Lung Neoplasms drug therapy, Lung Neoplasms pathology, Protein Kinase Inhibitors therapeutic use, Protein Kinase Inhibitors pharmacology, Point Mutation
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Activating point mutations in the MET tyrosine kinase domain (TKD) are oncogenic in a subset of papillary renal cell carcinomas. Here, using comprehensive genomic profiling among >600,000 patients, we identify activating MET TKD point mutations as putative oncogenic driver across diverse cancers, with a frequency of ∼0.5%. The most common mutations in the MET TKD defined as oncogenic or likely oncogenic according to OncoKB resulted in amino acid substitutions at positions H1094, L1195, F1200, D1228, Y1230, M1250, and others. Preclinical modeling of these alterations confirmed their oncogenic potential and also demonstrated differential patterns of sensitivity to type I and type II MET inhibitors. Two patients with metastatic lung adenocarcinoma harboring MET TKD mutations (H1094Y, F1200I) and no other known oncogenic drivers achieved confirmed partial responses to a type I MET inhibitor. Activating MET TKD mutations occur in multiple malignancies and may confer clinical sensitivity to currently available MET inhibitors. Significance: The identification of targetable genomic subsets of cancer has revolutionized precision oncology and offers patients treatments with more selective and effective agents. Here, we demonstrate that activating, oncogenic MET tyrosine kinase domain mutations are found across a diversity of cancer types and are responsive to MET tyrosine kinase inhibitors., (©2024 The Authors; Published by the American Association for Cancer Research.)
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- 2024
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11. Assessing external exposome by implementing an Environmental Data Management System using Open Data.
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Tagliaferro S, Maio S, Pirona F, Stanisci I, Sarno G, Silvi P, Kermenidou M, Papaioannou N, Perchard R, Prpic I, Polanska K, Jerzynska J, Ramos E, Rovira J, Belmonte J, Snoj Tratnik JS, Horvat M, Kocman D, Spiric Z, Zickella J, Fasola S, La Grutta S, Malizia V, Montalbano L, Baldacci S, and Annesi-Maesano I
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- Humans, Male, Female, Environmental Exposure, Data Management, Environmental Monitoring methods, Europe, Aged, 80 and over, Cities, Aged, Exposome
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Due to the increasing importance of exposome in environmental epidemiology, feasibility and usefulness of an Environmental Data Management System (EDMS) using Open Data was evaluated. The EDMS includes data from 10 European cities (Celje (Slovenia), Łódź (Poland), Manchester (UK), Palermo (Italy), Paris (France), Porto (Portugal), Regensburg (Germany), Reus (Spain), Rijeka (Croatia), Thessaloniki (Greece)) about external non-specific and specific exposome factors at the city or country level (2017-2020). Findings showed that the highest values of life expectancy were in Reus females (86 years) and Palermo males (81 years). UK had the highest obesity rate (28%), Croatia the highest prescribed drug consumption (62%), Greece and Portugal the highest smoking rates (37%, 42%) and daily alcohol consumption (21%), respectively. The most polluted cities were Thessaloniki for PM
10 (38 µg/m3 ), Łódź for PM2.5 (25 µg/m3 ), Porto for NO2 (62 µg/m3 ) and Rijeka for O3 (92 µg/m3 ). Thessaloniki had the highest grey space (98%) and Łódź the highest cumulative amount of pollen (39,041 p/m3 ). The highest daily noise levels ≥ 55 dB was in Reus (81% to traffic) and Regensburg (21% to railway). In drinking water, arsenic had the highest value in Thessaloniki (6.4 µg/L), boron in Celje (24 mg/L) and lead in Paris (46.7 µg/L). Portugal and Greece showed the highest pesticide residues in food (7%). In conclusion, utilizing open-access databases enables the translation of research findings into actionable strategies for public health interventions., (© 2024. The Author(s).)- Published
- 2024
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12. The Association of Prenatal Diagnoses with Mortality and Long-Term Morbidity in Children with Specific Isolated Congenital Anomalies: A European Register-Based Cohort Study.
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Heino A, Morris JK, Garne E, Baldacci S, Barisic I, Cavero-Carbonell C, García-Villodre L, Given J, Jordan S, Loane M, Lutke LR, Neville AJ, Santoro M, Scanlon I, Tan J, de Walle HEK, Kiuru-Kuhlefelt S, and Gissler M
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- Humans, Female, Infant, Newborn, Pregnancy, Male, Infant, Cohort Studies, Morbidity trends, Gestational Age, Congenital Abnormalities mortality, Congenital Abnormalities epidemiology, Congenital Abnormalities diagnosis, Europe epidemiology, Infant Mortality trends, Child, Preschool, Hernias, Diaphragmatic, Congenital mortality, Hernias, Diaphragmatic, Congenital diagnosis, Length of Stay statistics & numerical data, Gastroschisis mortality, Gastroschisis diagnosis, Gastroschisis epidemiology, Survival Rate, Registries, Prenatal Diagnosis methods, Prenatal Diagnosis statistics & numerical data
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Objectives: To compare 5-year survival rate and morbidity in children with spina bifida, transposition of great arteries (TGA), congenital diaphragmatic hernia (CDH) or gastroschisis diagnosed prenatally with those diagnosed postnatally., Methods: Population-based registers' data were linked to hospital and mortality databases., Results: Children whose anomaly was diagnosed prenatally (n = 1088) had a lower mean gestational age than those diagnosed postnatally (n = 1698) ranging from 8 days for CDH to 4 days for TGA. Children with CDH had the highest infant mortality rate with a significant difference (p < 0.001) between those prenatally (359/1,000 births) and postnatally (116/1,000) diagnosed. For all four anomalies, the median length of hospital stay was significantly greater in children with a prenatal diagnosis than those postnatally diagnosed. Children with prenatally diagnosed spina bifida (79% vs 60%; p = 0.002) were more likely to have surgery in the first week of life, with an indication that this also occurred in children with CDH (79% vs 69%; p = 0.06)., Conclusions: Our findings do not show improved outcomes for prenatally diagnosed infants. For conditions where prenatal diagnoses were associated with greater mortality and morbidity, the findings might be attributed to increased detection of more severe anomalies. The increased mortality and morbidity in those diagnosed prenatally may be related to the lower mean gestational age (GA) at birth, leading to insufficient surfactant for respiratory effort. This is especially important for these four groups of children as they have to undergo anaesthesia and surgery shortly after birth. Appropriate prenatal counselling about the time and mode of delivery is needed., (© 2024. The Author(s).)
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- 2024
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13. Hospital care in the first 10 years of life of children with congenital anomalies in six European countries: data from the EUROlinkCAT cohort linkage study.
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Morris JK, Loane M, Wahlich C, Tan J, Baldacci S, Ballardini E, Cavero-Carbonell C, Damkjær M, García-Villodre L, Gissler M, Given J, Gorini F, Heino A, Limb E, Lutke R, Neville A, Rissmann A, Scanlon L, Tucker DF, Urhoj SK, de Walle HE, and Garne E
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- Pregnancy, Child, Female, Humans, Europe epidemiology, Cohort Studies, Parturition, Registries, Heart Defects, Congenital epidemiology, Heart Defects, Congenital surgery, Congenital Abnormalities epidemiology
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Objective: To quantify the hospital care for children born with a major congenital anomaly up to 10 years of age compared with children without a congenital anomaly., Design, Setting and Patients: 79 591 children with congenital anomalies and 2 021 772 children without congenital anomalies born 1995-2014 in six European countries in seven regions covered by congenital anomaly registries were linked to inpatient electronic health records up to their 10th birthday., Main Outcome Measures: Number of days in hospital and number of surgeries., Results: During the first year of life among the seven regions, a median of 2.4% (IQR: 2.3, 3.2) of children with a congenital anomaly accounted for 18% (14, 24) of days in hospital and 63% (62, 76) of surgeries. Over the first 10 years of life, the percentages were 17% (15, 20) of days in hospital and 20% (19, 22) of surgeries. Children with congenital anomalies spent 8.8 (7.5, 9.9) times longer in hospital during their first year of life than children without anomalies (18 days compared with 2 days) and 5 (4.1-6.1) times longer aged, 5-9 (0.5 vs 0.1 days). In the first year of life, children with gastrointestinal anomalies spent 40 times longer and those with severe heart anomalies 20 times longer in hospital reducing to over 5 times longer when aged 5-9., Conclusions: Children with a congenital anomaly consume a significant proportion of hospital care resources. Priority should be given to public health primary prevention measures to reduce the risk of congenital anomalies., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
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- 2024
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14. Medication use during pregnancy and the risk of gastroschisis: a systematic review and meta-analysis of observational studies.
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Baldacci S, Santoro M, Mezzasalma L, Pierini A, and Coi A
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- Female, Humans, Pregnancy, Aspirin, Contraceptives, Oral, Ibuprofen, Phenylpropanolamine adverse effects, Pseudoephedrine, Observational Studies as Topic, Gastroschisis epidemiology, Gastroschisis chemically induced
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Objectives: The aetiology of gastroschisis is considered multifactorial. We conducted a systematic review and meta-analysis to assess whether the use of medications during pregnancy, is associated with the risk of gastroschisis in offspring., Methods: PubMed, EMBASE, and Scopus were searched from 1st January 1990 to 31st December 2020 to identify observational studies examining the association between medication use during pregnancy and the risk of gastroschisis. The Newcastle-Ottawa Scale was used for the quality assessment of the individual studies. We pooled adjusted measures using a random-effect model to estimate relative risk [RR] and the 95% confidence interval [CI]. I
2 statistic for heterogeneity and publication bias was calculated., Results: Eighteen studies providing data on 751,954 pregnancies were included in the meta-analysis. Pooled RRs showed significant associations between aspirin (RR 1.66, 95% CI 1.16-2.38; I2 = 58.3%), oral contraceptives (RR 1.52, 95% CI 1.21-1.92; I2 = 22.0%), pseudoephedrine and phenylpropanolamine (RR 1.51, 95% CI 1.16-1.97; I2 = 33.2%), ibuprofen (RR 1.42, 95% CI 1.26-1.60; I2 = 0.0%), and gastroschisis. No association was observed between paracetamol and gastroschisis (RR 1.16, 95% CI 0.96-1.41; I2 = 39.4%)., Conclusions: These results suggest that the exposure in the first trimester of pregnancy to over the counter medications (OTC) such as aspirin, ibuprofen, pseudoephedrine and phenylpropanolamine as well as to oral contraceptives, was associated with an increased risk of gastroschisis. However, these associations are significant only in particular subgroups defined by geographic location, adjustment variables and type of control. Therefore, further research is needed to investigate them as potential risk factors for gastroschisis, to assess their safety in pregnancy and to develop treatment strategies to reduce the risk of gastroschisis in offspring. PROSPERO registration number: CRD42021287529., (© 2024. The Author(s).)- Published
- 2024
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