{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T02:18:00Z","timestamp":1787192280332,"version":"build-2736575974"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,10,13]],"date-time":"2022-10-13T00:00:00Z","timestamp":1665619200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Nutr."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Maternal diet during pregnancy has been linked to offspring allergy risk and it could represent a potential target for allergy prevention. The Mediterranean Diet (MD) is considered one of the healthiest dietary models. Randomized-controlled trials on the effect of MD in preventing pediatric allergic diseases are still needed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and analysis<\/jats:title><jats:p>The Mediterranean Diet during Pregnancy study (PREMEDI) will be a 9-month multi-center, randomized-controlled, parallel groups, prospective trial. Healthy women (20\u201335 years) at their first trimester of pregnancy at risk for atopy baby, will be randomly allocated to Group 1 (standard obstetrical and gynecological follow-up and nutritional counseling to promote MD) or Group 2 (standard obstetrical and gynecological follow-up alone). 138 mother-child pair per group will be needed to detect a reduction in cumulative incidence of \u22651 allergic disease at 24 months of age. The primary study aim will be the evaluation of the occurrence of allergic disorders in the first 24 months of life. The secondary aims will be the evaluation of maternal weight gain, pregnancy\/perinatal complications, growth indices and occurrence of other chronic disorders, mother-child pair adherence to MD and gut microbiome features, breastfeeding duration and breast milk composition, epigenetic modulation of genes involved in immune system, and metabolic pathways in the offspring.<\/jats:p><\/jats:sec><jats:sec><jats:title>Ethics and dissemination<\/jats:title><jats:p>The study protocol has been approved by the Ethics Committee of the University of Naples Federico II (number 283\/21) and it will be conducted in accordance with the Helsinki Declaration (Fortaleza revision, 2013), the Good Clinical Practice Standards (CPMP\/ICH\/135\/95), the Italian Decree-Law 196\/2003 regarding personal data and the European regulations on this subject. The study has been registered in the Clinical Trials Protocol Registration System.<\/jats:p><\/jats:sec><jats:sec><jats:title>Clinical trial registration<\/jats:title><jats:p>[<jats:ext-link>http:\/\/clinicaltrials.gov<\/jats:ext-link>], identifier [NCT05119868].<\/jats:p><\/jats:sec>","DOI":"10.3389\/fnut.2022.951223","type":"journal-article","created":{"date-parts":[[2022,10,13]],"date-time":"2022-10-13T09:56:08Z","timestamp":1665654968000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Effects of the Mediterranean Diet during pregnancy on the onset of allergy in at risk children: A study protocol of a multi-center, randomized- controlled, parallel groups, prospective trial (the PREMEDI study)"],"prefix":"10.3389","volume":"9","author":[{"given":"Serena","family":"Coppola","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorella","family":"Paparo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Chiariotti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danilo","family":"Ercolini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rita","family":"Nocerino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Fiorenza","family":"de Giovanni di Santa Severina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Carucci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"De Filippis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annalisa","family":"Agangi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcello","family":"Napolitano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annalisa","family":"Passariello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Messina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Berni Canani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,10,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"889","DOI":"10.1111\/pai.13303","article-title":"Dietary factors during pregnancy and atopic outcomes in childhood: A systematic review from the European academy of allergy and clinical immunology.","volume":"31","author":"Venter","year":"2020","journal-title":"Pediatr Allergy Immunol."},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3390\/nu14020282","article-title":"Early life and nutrition and allergy development.","volume":"14","author":"Vandenplas","year":"2022","journal-title":"Nutrients."},{"key":"B3","doi-asserted-by":"publisher","first-page":"218","DOI":"10.20960\/nh.02453","article-title":"The first 1000 days: An opportunity to reduce the burden of noncommunicable diseases.","volume":"36","author":"Moreno Villares","year":"2019","journal-title":"Nutr Hosp."},{"key":"B4","doi-asserted-by":"publisher","first-page":"1812","DOI":"10.1136\/gutjnl-2015-309957","article-title":"High-level adherence to a Mediterranean diet beneficially impacts the gut microbiota and associated metabolome.","volume":"65","author":"De Filippis","year":"2016","journal-title":"Gut."},{"key":"B5","doi-asserted-by":"publisher","first-page":"11678","DOI":"10.3390\/ijms150711678","article-title":"Mediterranean diet and health: Food effects on gut microbiota and disease control.","volume":"15","author":"Del Chierico","year":"2014","journal-title":"Int J Mol Sci."},{"key":"B6","doi-asserted-by":"publisher","first-page":"2809","DOI":"10.1016\/j.celrep.2016.05.047","article-title":"Dietary fiber and bacterial SCFA enhance oral tolerance and protect against food allergy through diverse cellular pathways.","volume":"15","author":"Tan","year":"2016","journal-title":"Cell Rep."},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2020.01244","article-title":"Allergy modulation by N-3 long chain polyunsaturated fatty acids and fat soluble nutrients of the mediterranean diet.","volume":"11","author":"Hogenkamp","year":"2020","journal-title":"Front Pharmacol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1136\/thx.2007.081745","article-title":"Mediterranean diet in pregnancy is protective for wheeze and atopy in childhood.","volume":"63","author":"Chatzi","year":"2008","journal-title":"Thorax."},{"key":"B9","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1002\/ppul.21205","article-title":"Olive oil during pregnancy is associated with reduced wheezing during the first year of life of the offspring.","volume":"45","author":"Castro-Rodriguez","year":"2010","journal-title":"Pediatr Pulmonol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"2058","DOI":"10.1017\/S0007114513001426","article-title":"Mediterranean diet adherence during pregnancy and risk of wheeze and eczema in the first year of life: INMA (Spain) and RHEA (Greece) mother-child cohort studies.","volume":"110","author":"Chatzi","year":"2013","journal-title":"Br J Nutr."},{"key":"B11","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.aller.2017.02.009","article-title":"Influence of the Mediterranean diet during pregnancy in the development of wheezing and eczema in infants in Pamplona.","volume":"46","author":"Alvarez Zallo","year":"2018","journal-title":"Spain. Allergol Immunopathol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"250.e","DOI":"10.1016\/j.jaci.2010.05.009","article-title":"Maternal dietary pattern during pregnancy is not associated with recurrent wheeze in children.","volume":"126","author":"Lange","year":"2010","journal-title":"J Allergy Clin Immunol."},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01215-2019","article-title":"Mediterranean diet during pregnancy and childhood respiratory and atopic outcomes: Birth cohort study.","volume":"55","author":"B\u00e9dard","year":"2020","journal-title":"Eur Respir J."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1310","DOI":"10.1111\/j.1398-9995.2008.01722.x","article-title":"Mediterranean diet is associated with reduced asthma and rhinitis in Mexican children.","volume":"63","author":"de Batlle","year":"2008","journal-title":"Allergy."},{"key":"B15","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1016\/j.aller.2015.12.002","article-title":"Effect of foods and Mediterranean diet during pregnancy and first years of life on wheezing, rhinitis and dermatitis in preschoolers.","volume":"44","author":"Castro-Rodriguez","year":"2916","journal-title":"Allergol Immunopathol."},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21051884","article-title":"Crosstalk among circadian rhythm, obesity and allergy.","volume":"21","author":"Orihara","year":"2020","journal-title":"Int J Mol Sci."},{"key":"B17","author":"Rasmussen","year":"2009","journal-title":"Weight gain during pregnancy: Reexamining the guidelines."},{"key":"B18","year":"2022","journal-title":"La Quarta Dose Per Gli Over 60 E Fondamentale"},{"key":"B19","doi-asserted-by":"publisher","first-page":"843","DOI":"10.1111\/pai.13496","article-title":"EAACI guideline: Preventing the development of food allergy in infants and young children (2020 update).","volume":"32","author":"Halken","year":"2021","journal-title":"Pediatr Allergy Immunol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"183.e","DOI":"10.1016\/j.jpeds.2021.01.059","article-title":"The impact of formula choice for the management of pediatric cow\u2019s milk allergy on the occurrence of other allergic manifestations: The atopic march cohort study.","volume":"232","author":"Nocerino","year":"2021","journal-title":"J Pediatr."},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.02730-2021","article-title":"Global initiative for asthma strategy 2021: Executive summary and rationale for key changes.","volume":"59","author":"Reddel","year":"2021","journal-title":"Eur Respir J."},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1186\/s13052-018-0525-6","article-title":"Diagnosis, treatment and prevention of pediatric obesity: Consensus position statement of the Italian society for pediatric endocrinology and diabetology and the Italian society of pediatrics.","volume":"44","author":"Valerio","year":"2018","journal-title":"Ital J Pediatr."},{"key":"B23","year":"2022","journal-title":"Seventh Framework Programme"},{"key":"B24","author":"Sherry","year":"2022","journal-title":"Human sequence removal national center for biotechnology information."},{"key":"B25","doi-asserted-by":"publisher","first-page":"863","DOI":"10.1093\/bioinformatics\/btr026","article-title":"Quality control and preprocessing of metagenomic datasets.","volume":"27","author":"Schmieder","year":"2011","journal-title":"Bioinformatics."},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.65088","article-title":"Integrating taxonomic, functional, and strain-level profiling of diverse microbial communities with bioBakery 3.","volume":"10","author":"Beghini","year":"2021","journal-title":"eLife."},{"key":"B27","doi-asserted-by":"publisher","first-page":"962","DOI":"10.1038\/s41592-018-0176-y","article-title":"Species-level functional profiling of metagenomes and metatranscriptomes.","volume":"15","author":"Franzosa","year":"2018","journal-title":"Nat Methods."},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1186\/s12859-016-1380-3","article-title":"ampliMethProfiler: A pipeline for the analysis of CpG methylation profiles of targeted deep bisulfite sequenced amplicons.","volume":"17","author":"Scala","year":"2016","journal-title":"BMC Bioinformatics."},{"key":"B29","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1111\/j.1399-3038.2011.01254.x","article-title":"The EuroPrevall birth cohort study on food allergy: Baseline characteristics of 12,000 newborns and their families from nine European countries.","volume":"23","author":"McBride","year":"2012","journal-title":"Pediatr Allergy Immunol."},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1004977","article-title":"Machine learning meta-analysis of large metagenomic datasets: Tools and biological insights.","volume":"12","author":"Pasolli","year":"2016","journal-title":"PLoS Comput Biol."},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-016-0926-z","article-title":"Systematic identification of genetic influences on methylation across the human life course.","volume":"17","author":"Gaunt","year":"2016","journal-title":"Genome Biol."},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2017.00072","article-title":"What are the effects of a mediterranean diet on allergies and asthma in children?","volume":"5","author":"Castro-Rodriguez","year":"2017","journal-title":"Front Pediatr."}],"container-title":["Frontiers in Nutrition"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2022.951223\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,10,13]],"date-time":"2022-10-13T09:56:12Z","timestamp":1665654972000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2022.951223\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,13]]},"references-count":32,"alternative-id":["10.3389\/fnut.2022.951223"],"URL":"https:\/\/doi.org\/10.3389\/fnut.2022.951223","relation":{},"ISSN":["2296-861X"],"issn-type":[{"value":"2296-861X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,13]]},"article-number":"951223"}}