{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T16:07:16Z","timestamp":1784304436213,"version":"3.55.0"},"reference-count":54,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T00:00:00Z","timestamp":1784246400000},"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>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To investigate the effects of a high-dose probiotic-lactoferrin (LF)-milk fat globule membrane (MFGM)-nucleotide combined formula on reducing the incidence risk of common diseases and related symptoms and improving growth and hemoglobin level in neonates born via cesarean section.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This trial was a prospective, multicenter, open-label, randomized, controlled 3-month intervention study. A total of 150 eligible neonates were enrolled. All participants completed the full intervention and provided clinical data. All enrolled formula-feeding neonates were randomly assigned to either the intervention group (IG,\n                      <jats:italic>n<\/jats:italic>\n                      = 50) or the control group (CG,\n                      <jats:italic>n<\/jats:italic>\n                      = 50), and 50 exclusively breastfed neonates were assigned to the breastfeeding control group (BCG). The formula used in the IG contained 2 \u00d7 10\n                      <jats:sup>9<\/jats:sup>\n                      CFU\/100 g probiotics, 200 mg\/100 g LF, added MFGM, and 55 mg\/100 g nucleotides. In contrast, neonates in the CG were fed a formula containing 45\u201350 mg\/100 g LF and 30\u201335 mg\/100 g nucleotides, without probiotic or MFGM fortification. The primary outcome was the frequency of upper respiratory tract infections (URTIs). Secondary outcomes included the incidence of other respiratory, gastrointestinal, and allergic symptoms and diseases, as well as infant anthropometric indicators (including length, weight and head circumference) and the hemoglobin (Hb) concentration.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Result<\/jats:title>\n                    <jats:p>\n                      The incidence of URTIs over the 3-month intervention showed no significant difference among the three groups [the incidences of URTIs in CG, IG, and BCG: 22% (11\/50), 18% (9\/50), and 14% (7\/50), respectively, \u03c7\n                      <jats:sup>2<\/jats:sup>\n                      = 1.084, p = 0.582] according to both intention-to-treat (TT) and per protocol (PP) analyses [incidence of URTIs in CG, IG, and BCG: 22.9% (11\/48), 19.6% (9\/46), and 14.9% (7\/47), respectively, \u03c7\n                      <jats:sup>2<\/jats:sup>\n                      = 0.680, p = 0.712]. After the 3-month intervention, compared with infants in the CG, infants in the IG showed a reduced risk ration (RR) for functional dyspepsia [RR = 0.756, 95% confidence interval (95% CI) = 0.587\u20130.974] and eczema (RR = 0.647, 95% CI = 0.449\u20130.933). Hb levels in the CG and IG were both significantly higher than those in the BCG (107.35 \u00b1 9.26 vs. 105.99 \u00b1 7.01 vs. 101.42 \u00b1 7.07 g\/L for CG, IG, and BCG, respectively;\n                      <jats:italic>F<\/jats:italic>\n                      = 9.629,\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt; 0.001), with no statistically significant difference between the CG and IG. No significant differences in anthropometric indicators were observed among the three groups (\n                      <jats:italic>p<\/jats:italic>\n                      &amp;gt; 0.05).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study found no adverse effects associated with 3-month supplementation of a high-dose probiotic-LF-MFGM-nucleotide combined formula, supporting its safety for term neonates delivered by cesarean section. The primary outcome, URTI incidence, did not differ significantly among groups. Exploratory analyses suggested lower risks of functional dyspepsia and eczema in the intervention group; however, these findings should be considered preliminary and require confirmation in larger adequately powered studies. The intervention was well tolerated and showed safety comparable to standard feeding practices.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnut.2026.1741431","type":"journal-article","created":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T15:36:21Z","timestamp":1784302581000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Effect of a high-dose bioactive components formula on reducing common diseases in term neonates delivered by cesarean section: a randomized, open-label, controlled trial"],"prefix":"10.3389","volume":"13","author":[{"given":"Ke","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Clinical Nutrition, Chengdu Women's & Children's Central Hospital, School of Medicine, University of Electronic Science and Technology of China","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Chengdu Women's & Children's Central Hospital, School of Medicine, University of Electronic Science and Technology of China","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haixia","family":"Chen","sequence":"additional","affiliation":[{"name":"Baoxing Central for Disease Prevention and Control","place":["Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nianyang","family":"He","sequence":"additional","affiliation":[{"name":"Department of Child Health Care, Xindu Maternal and Child Health Care Hospital","place":["Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuqi","family":"Tang","sequence":"additional","affiliation":[{"name":"Baoxing Central for Disease Prevention and Control","place":["Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Yang","sequence":"additional","affiliation":[{"name":"Baoxing Central for Disease Prevention and Control","place":["Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziji","family":"Fang","sequence":"additional","affiliation":[{"name":"Chengdu Women's & Children's Central Hospital, School of Medicine, University of Electronic Science and Technology of China","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changqi","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Exercise and Nutritional Sciences, San Diego State University","place":["San Diego, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1016\/S2352-4642(21)00311-4","article-title":"Global, regional, and national causes of under-5 mortality in 2000\u201319: an updated systematic analysis with implications for the Sustainable Development Goals","volume":"6","author":"Perin","year":"2022","journal-title":"Lancet Child Adolesc Health"},{"key":"B2","doi-asserted-by":"publisher","first-page":"100128","DOI":"10.1016\/j.advnut.2023.10.001","article-title":"Effects of early diet on the prevalence of allergic disease in children: a systematic review and meta-analysis","volume":"15","author":"Wang","year":"2024","journal-title":"Adv Nutr."},{"key":"B3","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.jaci.2015.03.048","article-title":"The allergy epidemics: 1870\u20132010","volume":"136","author":"Platts-Mills","year":"2015","journal-title":"J Allergy Clin Immunol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1111\/pai.12819","article-title":"Pediatric allergy and immunology in China","volume":"29","author":"Wong","year":"2018","journal-title":"Pediatr Allergy Immunol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"181","DOI":"10.3389\/fmed.2018.00181","article-title":"The vaginal microenvironment: the physiologic role of lactobacilli","volume":"5","author":"Amabebe","year":"2018","journal-title":"Front Med"},{"key":"B6","doi-asserted-by":"publisher","first-page":"946","DOI":"10.3390\/nu12040946","article-title":"The relationship between the infant gut microbiota and allergy. 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