It is not unusual to prescribe glucocorticoids to school children who were mostly formula- fed

It is not unusual to prescribe glucocorticoids to school children who were mostly formula- fed | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Short Report It is not unusual to prescribe glucocorticoids to school children who were mostly formula- fed Sergio Verd, Alicia-Esther Tur, Ana Ferragut, Elena Sol, Ignacio Pareja, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4869699/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background: There is mounting evidence on the harmful effects of glucocorticoid bursts prescribed to manage pediatric allergies or respiratory diseases. Therefore, minimizing glucocorticoid use in children deserves all possible support. Given that breastfeeding prevents infectious diseases and inflammation in children several years after the cessation of breastfeeding, we aimed to explore whether breastfeeding also prevents the prescription of glucocorticoids that occurs in these diseases. Method: This was a cross-sectional observational study in a primary care center of children who attended the well-child clinic at the beginning and end of primary school. Data on glucocorticoid prescription and information on breastfeeding duration were taken from these patients' medical files. Results: We recruited 95 children with accurate data on glucocorticoid prescriptions and breastfeeding duration. At least one burst of glucocorticoids was prescribed to 47% of schoolchildren. The median time to the first dose of glucocorticoids from birth was three years (IQR, 2-4 y.). Breastfeeding duration below three months was coupled with approximately three times as many days (7.85 vs. 2.77; P=0.031) and three times as many bursts (2.12 versus 0.77; P=0.012) of glucocorticoids compared to breastfeeding beyond three months. Conclusion: Previous studies have reported the reduction of acute illnesses that may or may not require glucocorticoids among previously breastfed children. Our study took a step further to report the reduction of glucocorticoid bursts among children who were breastfed beyond three months of age. If future studies confirm the results presented at this preliminary stage, the goal of limiting glucocorticoid bursts in ambulatory Paediatrics may be easier to achieve in previously breastfed children. Breastfeeding Asthma Laryngitis Exanthema Glucocorticoids Iatrogenic disease. INTRODUCTION Despite evidence of their adverse effects, systemic glucocorticoids (GC) continue to be widely prescribed in children attending Emergency Departments. Conversely, GC use is declining in non-acute settings, such as vasculitis or inflammatory bowel disease management [ 1 , 2 ]. Hence, a call has been launched to encourage clinical practice to reduce GC use [ 3 ]. Because GC has a spectrum of anti-inflammatory activity that involves both the humoral and cellular systems, it is crucial for the management of a wide array of inflammatory diseases. For more than a half-century, the benefit of the long-term use of GC was assessed against its well-known subsequent adverse events, including bleeding, infection, metabolic, eye, or heart conditions. Unlike conventional cautions against the above-mentioned side effects of extended use of GC, the prevailing view was that the risk of short courses of GC was negligible, to the extent that a 1997 review could state that it was limited to chickenpox complications [ 4 ]. As expected, in recent years, the risk-benefit balance of GC short courses has become better understood. Short courses of GC have been defined in different ways. Previous asthma guidelines advised short courses of up to 14 days, but the trend in current guidelines is to limit GC bursts to 7 days. A 2016 meta-analysis on the toxic effects of GC bursts in children has accepted as short courses those lasting less than 15 days [ 5 ]; this meta-analysis included 850 adverse reactions in a population of 3,200 paediatric patients and found that the most severe side effect associated with short courses of GC was infection (incidence 0.9%), with one child who died and other two were admitted to intensive care. In addition, 81% (43/53) of tested children showed transient biochemical hypothalamic-pituitary-adrenal axis suppression, and the list of adverse drug effects also included vomiting (5.4%), mood swings (4.7%), and sleep disturbances (4,3%). Since present guidance for the evaluation of harms emphasises the necessity of taking descriptive studies into account when evaluating safety outcomes [ 6 ], recent observational research on more than four million children that reported how GC bursts were associated with a 1.4- to 2.2-fold increase of bleeding, sepsis, and pneumonia in children within the first month following GC prescription [ 7 ] cannot go unmentioned. An area for improvement is to minimise the use of GC so that they are only prescribed if there is no safer alternative. The other not-so-obvious strategy to address medication safety concerns is to prevent the diseases that usually are treated with the very drugs that may cause adverse events. Evidence confirms protection against infection years after lactation has been discontinued. Breastfeeding shields infants in Western countries from respiratory tract infections [ 8 ], predicts a decreased prevalence of wheezing for children up to age six [ 9 ], and reduces respiratory illness beyond age seven [ 10 ], among other benefits regarding acute paediatric illness in the medium term. In light of the co-occurrence of respiratory illness and GC use, we have focused on the optimal duration of any breastfeeding to avoid GC prescription. METHODS Design. This retrospective evaluation of case notes was carried out in the ambulatory paediatric services of a health centre located on the outskirts of Palma, the main city of Majorca. This centre's outpatient clinics and emergency units care for 27,000 people, of whom 4,500 are children under 15 years of age. This is a secondary analysis that relies on data collected to explore the impact of infant feeding history on the electrocardiogram of schoolchildren [ 11 ]. Participants. We conducted a cross-sectional observational study with 95 children at the start and finish of primary school. Every child of this age who visited our well-child clinic between May and December 2022 was the subject of the study. Only children with autoimmune or neoplastic chronic disease or children under prescriptions for long-term steroid treatment were excluded. Data collection. Details on breastfeeding were gathered from the medical records, which reflect infant feeding data from discharge from the maternity hospital until the end of breastfeeding. The cohort included children whose breastfeeding data were monitored for longer than 6 months and up to a maximum of 10 months of age. We checked the database of our pediatric pharmacy for all oral or parenteral glucocorticoid (dexamethasone, methylprednisolone, prednisolone, and hydrocortisone) outpatient prescriptions written within the life course of these children from their neonatal discharge to their health check-up at the age of 6 or 12 years. Data on indications for GC use were available retrospectively; information on the outpatient episodes that led to these prescriptions was taken from our patients' medical files. Demographic and other clinical data were extracted from the local admission dataset. Statistical Analysis, We used convenience sampling of subjects who participated in the original research, which enabled this secondary Analysis of previous data. To ensure the highest level of technical rigor, we used R Version 4.3.3, to analyze the data. In all cases, the Kolmogorov-Smirnov test was applied to test for a normal distribution. The sample was described using central tendency measures. Exact or t-tests were used to compare dichotomous or continuous characteristics and outcomes of children according to the length of time they were breastfed. A P-value of less than 0.05 was deemed statistically significant, further reinforcing the robustness of our findings. Ethics. The study's protocol was thoroughly reviewed and approved by the Balearic institutional review board for Health and Medical Research (ECIAP-2023), ensuring that all ethical guidelines were strictly followed. The study was not deemed a Service Evaluation, so formal written consent was required from parents of all children, further demonstrating our commitment to ethical research practices. RESULTS We have recruited a sample of 95 primary school children with accurate data on GC prescriptions and breastfeeding duration. The average body mass index of these children was at the 47.75 th percentile (95% CI 42.10 to 53.40), their mean age was 11.14 years (95% CI 10.51 to 11.77), and there were 47 girls and 48 boys. Table 1 describes the characteristics of children according to the duration of breastfeeding. We found no significant differences in terms of age, gender, and somatometric properties between those who were breastfed for at least 89 days or exceeding 89 days and those who were breastfed for at least 179 days or exceeding 179 days. A total of 45/95 children (47%) were prescribed at least one burst of GC from birth to the school stage when they were, on average, around 11 years old; 21 were boys, and 24 were girls, and there was no association between gender and GC prescription. The median time to first dose of GC from birth was three years (IQR, 2-4 y.). Among the forty-five children prescribed GC, 47% (21/45) received this medicine due to wheezing conditions, 42% (18/45) for laryngitis, and 29% (13/45) due to a rash. GC was more likely to be prescribed in those breastfed for less than 90 days than in those breastfed for 90 days or more. Any duration of breastfeeding below three months was coupled with approximately three times as many days (7.85 vs. 2.77) and three times as many short courses (2.12 versus 0.77) of GC compared to breastfeeding beyond three months. In particular, breastfeeding for less than three months was significantly associated with more courses of GC for laryngitis (0.81 vs. 0.16; P=0.03), and there is also a trend towards more courses of GC due to rash (0.021 vs. 0.07; P=0.07) or wheezing conditions (0.92 vs. 0.37; P=0.16) (Table 2). On the other hand, our data show that any duration of breastfeeding ≥ 6 months was a weaker predictor of protection against GC prescription. This longer duration was only accompanied by fewer GC short courses overall (1,82 vs. 0.45; P=0.03) and a trend towards fewer GC bursts due to laryngitis (0.81 vs. 0.23; P=0.08), but there were no differences regarding GC prescription due to a rash or wheezing disorders (Table 3). DISCUSSION This analysis has found moderate observational evidence to suggest that breastfeeding for short durations or not at all is associated with a higher risk of GC prescription until the end of primary school. The first synthesis of corticosteroids in 1944 revolutionised the management of inflammation and allergy. Since that time, the association between asthma and GC has dominated both patient communities and the medical world [ 12 ] to the extent that past and ongoing studies on patients with asthma report alarming overuse of GC around the world [ 13 ]. A mere twenty years after their initial release, GC became better known. By 1960, along with more beneficial effects, irreversible toxic reactions were described. In the 1970s, the committed efforts to circumscribe the indications for GC were starting to show results [ 14 ]. Over the last decades, the evidence of a significant reduction of symptoms and hospital stays among children with croup who have been prescribed GC has remained unchanged [ 15 ]. However, research assessing the effectiveness of GC in wheezy toddlers has generated mixed results [ 16 ]. Current stepwise treatment approaches to children with asthma include GC as a final step in difficult-to-treat cases, so the provocative statement that "regular use of GC in asthma should be declared criminal" is nowadays repeated by clinicians who lead the management of both adults and children's asthma [ 17 ]. Finally, regarding children's most common allergic or viral rashes, current guidelines hardly recommend treating them with GC, and growing evidence points against treating anaphylaxis with GC [ 18 ]. Therefore, we are just left with selected cases to treat children attended in ambulatory Pediatrics with short courses of GC, i.e., chronic urticaria or closely monitored moderate to severe asthma in school children. This is a good reminder that although short GC courses must be prescribed cautiously due to their potentially harmful effects, most prescribed GC bursts are probably unnecessary [ 19 ]. Given the heterogeneity of information sources, it is not easy to accurately estimate the amount of GC prescribed to children. An attempt to improve the quality of these measurements and to monitor outpatient paediatric irrational drug prescribing has analysed homogenous databases from eleven member countries of the Organisation for Economic Co-operation and Development (OECD), where national health services reimburse drugs. The prevalence of pediatric outpatient prescriptions among these countries is comparable because the epidemiological patterns of the leading pediatric diseases are similar in OECD countries. This report shows recent prednisolone dispensation data from only two countries; in France, 11% of children were prescribed this drug each year, and in New Zealand, 6% [ 20 ]. These figures align with our results that GC has been prescribed to 47% of our children over eleven years of follow-up. We found that 45 children were prescribed a short course of GC for respiratory or cutaneous symptoms; twenty-one children had asthma or asthma-like conditions, eighteen had acute laryngitis, and thirteen attended the clinic because of a rash. Children who no longer breastfed at three months of age have been prescribed GC about three times as often and for three times as many days as children who breastfed for a more extended period. The length of any breastfeeding period below six months was also significantly associated with triple courses of GC. There was a trend towards triple the number of days on GC compared to more extended breastfeeding. The established fact of improved protection against infections years after lactation ends [ 20 , 10 ] points to a potential explanation for these findings. There are two categories of health benefits associated with breastfeeding: immediate benefits that infants or children receive while they are breastfed; and future benefits that manifest after breastfeeding has stopped. Most research on future benefits of breastfeeding has focused on non-communicable diseases and enhanced neurodevelopment. However, more and more academic research is being done on the reduced rate of infection or allergy among school children who were breastfed early in life. For children aged up to 18 months, breastfeeding within any 3-month period is inversely associated with the odds of laryngitis or tracheitis [ 21 ]. Exclusive breastfeeding for at least 3 months plays a preventive role against the development of allergic rhinitis [ 22 ], this reduced risk is evident in children under 5 years of age, but not beyond this age [ 23 ]. Breastfeeding is associated with a decreased risk of otitis spanning from infancy even up to the age of 4 years [ 24 , 25 ]. Research among 6-year-old children has reported that wheezing seems to be reduced by approximately half when children were breastfed for ≥ 6 months [ 9 ]. Cohorts from Canada, Sweden, United States and Australia have consistently showed that breastfeeding is associated with lower rates of wheezing or probable asthma in infants and toddlers [ 26 ]. To summarise, over 80% of the selected studies in a systematic review indicate that breastfeeding shields newborns from respiratory tract infections [ 8 ]. Regarding cutaneous conditions, evidence also supports that breastfeeding for 3–4 months lowers the incidence of eczema in the first two years of life [ 27 ]. The developmental origins of the disease hypothesis propose that nutritional or environmental exposures can program permanent long-term changes in metabolism that affect susceptibility to diseases [ 28 ]. According to the above hypothesis, breastfeeding may help to build resistance against a cluster of diseases, for which worldwide paediatric guidelines recommend bursts of GC generating high prescription numbers. While making this comment, we cannot ignore that since breastfeeding is socially patterned, lifestyle is an essential confounder in early feeding research, and socioeconomic factors can influence disease development or attitudes towards medication through multiple mechanisms other than human lactation itself. If future studies confirm the results presented at this preliminary stage, the universal goal to outlaw GC short courses that have become commonplace in ambulatory Paediatrics may be easier to achieve in children who were breastfed beyond three months of age, LIMITATIONS Several limitations should be taken into consideration in our analysis. Our observational design does not allow for causal inference. Data on noncompliance with medication are unknown in studies based on registry data. Lifestyle factors, including daycare attendance, siblings, exposure to tobacco smoke, housing, and body mass index, are not available in our database. The number of children with follow-up data for infant feeding type and GC prescription was limited. Therefore, our study did not have enough power to show adjusted statistically significant differences. Many factors affect the decision to prescribe GC; several are not gathered in our study. For example, we did not collect information about health system or health literacy characteristics, parental and physician attitudes toward drugs, continuous education, differences in clinical guidelines, or drug regulatory policies. A strength of this study was using a dataset with prescription data from community pharmacies throughout the island of Majorca. However, this study was limited to children who sought health care in the community. Hence, we have not collected data provided by hospital pharmacies, which might have led to an underestimation of the rates of GC. CONCLUSION Previous studies have reported benefits of breastfeeding on childhood infectious or allergic morbidity in the medium term. Our study took another step to assess the association of early infant feeding type with GC bursts prescribed to treat the above mentioned conditions. We found that the length of any breastfeeding below three or below six months is linked to three times as many GC bursts up to roughly 11 years of age. We also estimate that half of the children in our sample have been prescribed GC due to diseases for which this is often not the ideal treatment. There may be occasions of irrational prescribing to children in the first years of life because of numerous symptoms due to self-limited diseases. Further studies are needed to challenge the validity of these findings in other pediatric populations. Abbreviations GC systemic glucocorticoids OECD Organisation for Economic Co-operation and Development. Declarations Acknowledgements The authors acknowledge all the parents and children for their participation.Further, the authors are grateful to the staff of Bibliosalut, the Medical Balearic Library. We also appreciate the skilled voluntary help from the staff of La Vileta pediatric services. Authors’ contributions AF and ES had full access to all the data in the study and take responsibility for the integrity of the data. Study concept and design: MM and SV. Acquisition, analysis, or interpretation of data: AF and ES. Literature review and drafting of the manuscript: AT, IP and SV. All authors approved the final manuscript for submission. Funding Unfunded research. No competing financial interests exist for the authors. Availability of data and materials The datasets generated and/or analysed during the current study are not publicly available since patients could be identified by knowing their date of birth and date of attending the health service, but are available from the corresponding author on reasonable request. Ethics approval and consent to participate The Manuscripts includes a statement on ethics approval and consent, it includes the name of the ethics committee that approved the study. The study's protocol was reviewed and approved by the Balearic institutional review board for Health and Medical Research (ECIAP-2023). Consent for publication Not applicable. Competing interests The authors declare that they have no competing interests. References Dhaun N, McAdoo SP. The changing role of glucocorticoids in the treatment of anti-neutrophil cytoplasmic antibody-associated vasculitis. Kidney Int. 2022;101(2):201-204. httpsdoi: 10.1016/j.kint.2021.11.006. PMID: 35065686. 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The Effects of Early Nutritional Interventions on the Development of Atopic Disease in Infants and Children: The Role of Maternal Dietary Restriction, Breastfeeding, Hydrolyzed Formulas, and Timing of Introduction of Allergenic Complementary Foods. Pediatrics. 2019;143(4):e20190281. https://doi: 10.1542/peds.2019-0281. Barker, D.J. The fetal and infant origins of adult disease. BMJ 1990, 301, 1111. Tables Table 1 Demographic and somatometric data by mixed breastfeeding duration. Data are mean (SD) unless otherwise specified. VARIABLE Group 1, cut-off at 90 days Group 2, cut-off at 180 days Bf 90 days Bf 180 days Age (years) 11.04 (3.16) 11.26 (3.02) NS 11.12 (3.08) 11.20 (3.15) NS Girls//boys 26//27 21//22 NS 36//37 10//12 NS Weight percentile 53.24 (28.36) 56.81 (26.57) NS 54.75 (27.62) 55.19 (27.62) NS Height percentile 64.17 (25.97) 64.60 (25.95) NS 64.88 (25.39) 64.60 (25.95) NS BMI percentile 47.32 (28.50) 48.26 (26.12) NS 48.49 (28.31) 45.24 (24.00) NS ABBREVIATIONS: Bf, mixed breastfeeding; BMI, body mass index; NS, non significant. Table 2. Glucocorticoid courses in schoolchildren who have been breastfed up to or beyond the age of 90 days. VARIABLE Mixed breastfeeding 90 days mean (SD) Total number of days on GC treatment 7.85 (14,81) 2.77 (3.91) 0.031* Total number of GC courses 2.12 (3,29) 0.77 (1.13) 0.012* GC courses for acute bronchitis 0.92 (2,40) 0.37 (0.85) 0.16 GC courses for acute laringitis 0.81 (1,92) 0.16 (0.57) 0.036* GC courses for rash 0.21 (0,46) 0.07 (0.26) 0.07 Mixed breastfeeding duration 10.19 (18.19) 167.91 (56.83) 0.0001**** Significance derived from t test of means. ABBREVIATIONS: *<=0.05; ****<=0.0001; GC, Glucocorticoids; SD, standard deviation. Table 3. Glucocorticoid courses in schoolchildren who have been breastfed up to or beyond the age of 180 days. VARIABLE Mixed breastfeeding 180 days mean (SD) Total number of days on GC treatment 6.68 (12.82) 1.77 (2.96) 0.08 Total number of GC courses 1.82 (2.90) 0.45 (0.80) 0,03* GC courses for acute bronchitis 0.81 (2.09) 0.23 (0.69) 0.21 GC courses for acute laringitis 0.66 (1.69) 0.05 (0.21) 0.09 GC courses for rash 0.16 (0.41) 0.09 (0.29) 0.44 Mixed breastfeeding duration 42.00 (54.17) 212.91 (39.57) 0.0001**** Significance derived from t test of means. ABBREVIATIONS: **** <=0.0001; GC, Glucocorticoids; SD, standard deviation. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4869699","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Short Report","associatedPublications":[],"authors":[{"id":348796691,"identity":"b0178272-3c87-4d18-a0f5-41bb0060a214","order_by":0,"name":"Sergio Verd","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAwElEQVRIiWNgGAWjYDCCA2CSWQ7MfkCKFmMwO4EULYkNIIooLXy3jz+T+LjHOn1+2OGHQFvs5HQbCGiRPJdjJjnjWXruxttpBkAtycZmBwhoMTjDw2zMc+Bw7sbZCSAtBxK3EdbC/tj4z4HD6Yaz0z8Qq4XB8DHDgcMJ8tI5RNoieYbH8GHPgXTDDdI5BQcSDIjwC98Z9gcHfhywlpefnb75w4cKOzmCWhAuBKs0IFY5CMg3kKJ6FIyCUTAKRhQAANaqSX3I8mpnAAAAAElFTkSuQmCC","orcid":"","institution":"Balearic Islands Health Research Institute (IdISBa)","correspondingAuthor":true,"prefix":"","firstName":"Sergio","middleName":"","lastName":"Verd","suffix":""},{"id":348796692,"identity":"734acc1f-d4f7-428a-bf21-2df2d11e829d","order_by":1,"name":"Alicia-Esther Tur","email":"","orcid":"","institution":"Servei de Salut de les Illes Balears","correspondingAuthor":false,"prefix":"","firstName":"Alicia-Esther","middleName":"","lastName":"Tur","suffix":""},{"id":348796693,"identity":"df890827-6cda-4569-a525-1e1efda2c0ae","order_by":2,"name":"Ana Ferragut","email":"","orcid":"","institution":"Servei de Salut de les Illes Balears","correspondingAuthor":false,"prefix":"","firstName":"Ana","middleName":"","lastName":"Ferragut","suffix":""},{"id":348796694,"identity":"5b85fe54-d07a-406a-832a-19aa8e815db4","order_by":3,"name":"Elena Sol","email":"","orcid":"","institution":"Son Llatzer Hospital","correspondingAuthor":false,"prefix":"","firstName":"Elena","middleName":"","lastName":"Sol","suffix":""},{"id":348796696,"identity":"df387846-74dd-4a01-b51e-6dbcb128b97f","order_by":4,"name":"Ignacio Pareja","email":"","orcid":"","institution":"Servei de Salut de les Illes Balears","correspondingAuthor":false,"prefix":"","firstName":"Ignacio","middleName":"","lastName":"Pareja","suffix":""},{"id":348796697,"identity":"635ab722-4abe-41b9-85e6-c691b59d50f4","order_by":5,"name":"Marianna Mambie","email":"","orcid":"","institution":"Servei de Salut de les Illes Balears","correspondingAuthor":false,"prefix":"","firstName":"Marianna","middleName":"","lastName":"Mambie","suffix":""}],"badges":[],"createdAt":"2024-08-06 15:51:08","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4869699/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4869699/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":79476424,"identity":"6df0f428-b997-4d78-a0c4-28883c1ff630","added_by":"auto","created_at":"2025-03-29 03:01:26","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":384217,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4869699/v1/ac02d7d0-c4d0-456b-a9d9-8372d4a4a98c.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"It is not unusual to prescribe glucocorticoids to school children who were mostly formula- fed","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eDespite evidence of their adverse effects, systemic glucocorticoids (GC) continue to be widely prescribed in children attending Emergency Departments. Conversely, GC use is declining in non-acute settings, such as vasculitis or inflammatory bowel disease management [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Hence, a call has been launched to encourage clinical practice to reduce GC use [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eBecause GC has a spectrum of anti-inflammatory activity that involves both the humoral and cellular systems, it is crucial for the management of a wide array of inflammatory diseases. For more than a half-century, the benefit of the long-term use of GC was assessed against its well-known subsequent adverse events, including bleeding, infection, metabolic, eye, or heart conditions.\u003c/p\u003e \u003cp\u003eUnlike conventional cautions against the above-mentioned side effects of extended use of GC, the prevailing view was that the risk of short courses of GC was negligible, to the extent that a 1997 review could state that it was limited to chickenpox complications [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAs expected, in recent years, the risk-benefit balance of GC short courses has become better understood. Short courses of GC have been defined in different ways. Previous asthma guidelines advised short courses of up to 14 days, but the trend in current guidelines is to limit GC bursts to 7 days. A 2016 meta-analysis on the toxic effects of GC bursts in children has accepted as short courses those lasting less than 15 days [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]; this meta-analysis included 850 adverse reactions in a population of 3,200 paediatric patients and found that the most severe side effect associated with short courses of GC was infection (incidence 0.9%), with one child who died and other two were admitted to intensive care. In addition, 81% (43/53) of tested children showed transient biochemical hypothalamic-pituitary-adrenal axis suppression, and the list of adverse drug effects also included vomiting (5.4%), mood swings (4.7%), and sleep disturbances (4,3%). Since present guidance for the evaluation of harms emphasises the necessity of taking descriptive studies into account when evaluating safety outcomes [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e], recent observational research on more than four million children that reported how GC bursts were associated with a 1.4- to 2.2-fold increase of bleeding, sepsis, and pneumonia in children within the first month following GC prescription [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e] cannot go unmentioned.\u003c/p\u003e \u003cp\u003eAn area for improvement is to minimise the use of GC so that they are only prescribed if there is no safer alternative. The other not-so-obvious strategy to address medication safety concerns is to prevent the diseases that usually are treated with the very drugs that may cause adverse events. Evidence confirms protection against infection years after lactation has been discontinued. Breastfeeding shields infants in Western countries from respiratory tract infections [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e], predicts a decreased prevalence of wheezing for children up to age six [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e], and reduces respiratory illness beyond age seven [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e], among other benefits regarding acute paediatric illness in the medium term.\u003c/p\u003e \u003cp\u003eIn light of the co-occurrence of respiratory illness and GC use, we have focused on the optimal duration of any breastfeeding to avoid GC prescription.\u003c/p\u003e"},{"header":"METHODS","content":"\u003cp\u003eDesign.\u003c/p\u003e \u003cp\u003eThis retrospective evaluation of case notes was carried out in the ambulatory paediatric services of a health centre located on the outskirts of Palma, the main city of Majorca. This centre's outpatient clinics and emergency units care for 27,000 people, of whom 4,500 are children under 15 years of age. This is a secondary analysis that relies on data collected to explore the impact of infant feeding history on the electrocardiogram of schoolchildren [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eParticipants.\u003c/p\u003e \u003cp\u003eWe conducted a cross-sectional observational study with 95 children at the start and finish of primary school. Every child of this age who visited our well-child clinic between May and December 2022 was the subject of the study. Only children with autoimmune or neoplastic chronic disease or children under prescriptions for long-term steroid treatment were excluded.\u003c/p\u003e \u003cp\u003eData collection.\u003c/p\u003e \u003cp\u003eDetails on breastfeeding were gathered from the medical records, which reflect infant feeding data from discharge from the maternity hospital until the end of breastfeeding. The cohort included children whose breastfeeding data were monitored for longer than 6 months and up to a maximum of 10 months of age. We checked the database of our pediatric pharmacy for all oral or parenteral glucocorticoid (dexamethasone, methylprednisolone, prednisolone, and hydrocortisone) outpatient prescriptions written within the life course of these children from their neonatal discharge to their health check-up at the age of 6 or 12 years. Data on indications for GC use were available retrospectively; information on the outpatient episodes that led to these prescriptions was taken from our patients' medical files. Demographic and other clinical data were extracted from the local admission dataset.\u003c/p\u003e \u003cp\u003eStatistical Analysis,\u003c/p\u003e \u003cp\u003e We used convenience sampling of subjects who participated in the original research, which enabled this secondary Analysis of previous data. To ensure the highest level of technical rigor, we used R Version 4.3.3, to analyze the data. In all cases, the Kolmogorov-Smirnov test was applied to test for a normal distribution. The sample was described using central tendency measures. Exact or t-tests were used to compare dichotomous or continuous characteristics and outcomes of children according to the length of time they were breastfed. A P-value of less than 0.05 was deemed statistically significant, further reinforcing the robustness of our findings.\u003c/p\u003e \u003cp\u003eEthics.\u003c/p\u003e \u003cp\u003e The study's protocol was thoroughly reviewed and approved by the Balearic institutional review board for Health and Medical Research (ECIAP-2023), ensuring that all ethical guidelines were strictly followed. The study was not deemed a Service Evaluation, so formal written consent was required from parents of all children, further demonstrating our commitment to ethical research practices.\u003c/p\u003e"},{"header":"RESULTS","content":"\u003cp\u003eWe have recruited a sample of 95 primary school children with accurate data on GC prescriptions and breastfeeding duration. The average body mass index of these children was at the 47.75\u003csup\u003eth\u003c/sup\u003e percentile (95% CI 42.10 to 53.40), their mean age was 11.14 years (95% CI 10.51 to 11.77), and there were 47 girls and 48 boys.\u003c/p\u003e\n\u003cp\u003eTable 1 describes the characteristics of children according to the duration of breastfeeding. We found no significant differences in terms of age, gender, and somatometric properties between those who were breastfed for at least 89 days or exceeding 89 days and those who were breastfed for at least 179 days or exceeding 179 days.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eA total of 45/95 children (47%) were prescribed at least one burst of GC from birth to the school stage when they were, on average, around 11 years old; 21 were boys, and 24 were girls, and there was no association between gender and GC prescription. The median time to first dose of GC from birth was three years (IQR, 2-4 y.). Among the forty-five children prescribed GC, 47% (21/45) received this medicine due to wheezing conditions, 42% (18/45) for laryngitis, and 29% (13/45) due to a rash.\u003c/p\u003e\n\u003cp\u003eGC was more likely to be prescribed in those breastfed for less than 90 days than in those breastfed for 90 days or more. Any duration of breastfeeding below three months was coupled with approximately three times as many days (7.85 vs. 2.77) and three times as many short courses (2.12 versus 0.77) of GC compared to breastfeeding beyond three months. In particular, breastfeeding for less than three months was significantly associated with more courses of GC for laryngitis (0.81 vs. 0.16; P=0.03), and there is also a trend towards more courses of GC due to rash (0.021 vs. 0.07; P=0.07) or wheezing conditions (0.92 vs. 0.37; P=0.16) (Table 2).\u003c/p\u003e\n\u003cp\u003eOn the other hand, our data show that any duration of breastfeeding ≥ 6 months was a weaker predictor of protection against GC prescription. This longer duration was only accompanied by fewer GC short courses overall (1,82 vs. 0.45; P=0.03) and a trend towards fewer GC bursts due to laryngitis (0.81 vs. 0.23; P=0.08), but there were no differences regarding GC prescription due to a rash or wheezing disorders (Table 3).\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eThis analysis has found moderate observational evidence to suggest that breastfeeding for short durations or not at all is associated with a higher risk of GC prescription until the end of primary school.\u003c/p\u003e \u003cp\u003eThe first synthesis of corticosteroids in 1944 revolutionised the management of inflammation and allergy. Since that time, the association between asthma and GC has dominated both patient communities and the medical world [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e] to the extent that past and ongoing studies on patients with asthma report alarming overuse of GC around the world [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. A mere twenty years after their initial release, GC became better known. By 1960, along with more beneficial effects, irreversible toxic reactions were described. In the 1970s, the committed efforts to circumscribe the indications for GC were starting to show results [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eOver the last decades, the evidence of a significant reduction of symptoms and hospital stays among children with croup who have been prescribed GC has remained unchanged [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. However, research assessing the effectiveness of GC in wheezy toddlers has generated mixed results [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Current stepwise treatment approaches to children with asthma include GC as a final step in difficult-to-treat cases, so the provocative statement that \"regular use of GC in asthma should be declared criminal\" is nowadays repeated by clinicians who lead the management of both adults and children's asthma [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Finally, regarding children's most common allergic or viral rashes, current guidelines hardly recommend treating them with GC, and growing evidence points against treating anaphylaxis with GC [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Therefore, we are just left with selected cases to treat children attended in ambulatory Pediatrics with short courses of GC, i.e., chronic urticaria or closely monitored moderate to severe asthma in school children. This is a good reminder that although short GC courses must be prescribed cautiously due to their potentially harmful effects, most prescribed GC bursts are probably unnecessary [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eGiven the heterogeneity of information sources, it is not easy to accurately estimate the amount of GC prescribed to children. An attempt to improve the quality of these measurements and to monitor outpatient paediatric irrational drug prescribing has analysed homogenous databases from eleven member countries of the Organisation for Economic Co-operation and Development (OECD), where national health services reimburse drugs. The prevalence of pediatric outpatient prescriptions among these countries is comparable because the epidemiological patterns of the leading pediatric diseases are similar in OECD countries. This report shows recent prednisolone dispensation data from only two countries; in France, 11% of children were prescribed this drug each year, and in New Zealand, 6% [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. These figures align with our results that GC has been prescribed to 47% of our children over eleven years of follow-up.\u003c/p\u003e \u003cp\u003eWe found that 45 children were prescribed a short course of GC for respiratory or cutaneous symptoms; twenty-one children had asthma or asthma-like conditions, eighteen had acute laryngitis, and thirteen attended the clinic because of a rash. Children who no longer breastfed at three months of age have been prescribed GC about three times as often and for three times as many days as children who breastfed for a more extended period. The length of any breastfeeding period below six months was also significantly associated with triple courses of GC. There was a trend towards triple the number of days on GC compared to more extended breastfeeding.\u003c/p\u003e \u003cp\u003eThe established fact of improved protection against infections years after lactation ends [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e] points to a potential explanation for these findings. There are two categories of health benefits associated with breastfeeding: immediate benefits that infants or children receive while they are breastfed; and future benefits that manifest after breastfeeding has stopped. Most research on future benefits of breastfeeding has focused on non-communicable diseases and enhanced neurodevelopment. However, more and more academic research is being done on the reduced rate of infection or allergy among school children who were breastfed early in life. For children aged up to 18 months, breastfeeding within any 3-month period is inversely associated with the odds of laryngitis or tracheitis [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Exclusive breastfeeding for at least 3 months plays a preventive role against the development of allergic rhinitis [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e], this reduced risk is evident in children under 5 years of age, but not beyond this age [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Breastfeeding is associated with a decreased risk of otitis spanning from infancy even up to the age of 4 years [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. Research among 6-year-old children has reported that wheezing seems to be reduced by approximately half when children were breastfed for \u0026ge;\u0026thinsp;6 months [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Cohorts from Canada, Sweden, United States and Australia have consistently showed that breastfeeding is associated with lower rates of wheezing or probable asthma in infants and toddlers [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. To summarise, over 80% of the selected studies in a systematic review indicate that breastfeeding shields newborns from respiratory tract infections [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Regarding cutaneous conditions, evidence also supports that breastfeeding for 3\u0026ndash;4 months lowers the incidence of eczema in the first two years of life [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe developmental origins of the disease hypothesis propose that nutritional or environmental exposures can program permanent long-term changes in metabolism that affect susceptibility to diseases [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. According to the above hypothesis, breastfeeding may help to build resistance against a cluster of diseases, for which worldwide paediatric guidelines recommend bursts of GC generating high prescription numbers. While making this comment, we cannot ignore that since breastfeeding is socially patterned, lifestyle is an essential confounder in early feeding research, and socioeconomic factors can influence disease development or attitudes towards medication through multiple mechanisms other than human lactation itself.\u003c/p\u003e \u003cp\u003eIf future studies confirm the results presented at this preliminary stage, the universal goal to outlaw GC short courses that have become commonplace in ambulatory Paediatrics may be easier to achieve in children who were breastfed beyond three months of age,\u003c/p\u003e"},{"header":"LIMITATIONS","content":"\u003cp\u003eSeveral limitations should be taken into consideration in our analysis. Our observational design does not allow for causal inference. Data on noncompliance with medication are unknown in studies based on registry data. Lifestyle factors, including daycare attendance, siblings, exposure to tobacco smoke, housing, and body mass index, are not available in our database. The number of children with follow-up data for infant feeding type and GC prescription was limited. Therefore, our study did not have enough power to show adjusted statistically significant differences. Many factors affect the decision to prescribe GC; several are not gathered in our study. For example, we did not collect information about health system or health literacy characteristics, parental and physician attitudes toward drugs, continuous education, differences in clinical guidelines, or drug regulatory policies.\u003c/p\u003e \u003cp\u003eA strength of this study was using a dataset with prescription data from community pharmacies throughout the island of Majorca. However, this study was limited to children who sought health care in the community. Hence, we have not collected data provided by hospital pharmacies, which might have led to an underestimation of the rates of GC.\u003c/p\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003ePrevious studies have reported benefits of breastfeeding on childhood infectious or allergic morbidity in the medium term. Our study took another step to assess the association of early infant feeding type with GC bursts prescribed to treat the above mentioned conditions. We found that the length of any breastfeeding below three or below six months is linked to three times as many GC bursts up to roughly 11 years of age. We also estimate that half of the children in our sample have been prescribed GC due to diseases for which this is often not the ideal treatment. There may be occasions of irrational prescribing to children in the first years of life because of numerous symptoms due to self-limited diseases. Further studies are needed to challenge the validity of these findings in other pediatric populations.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eGC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003esystemic glucocorticoids\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eOECD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eOrganisation for Economic Co-operation and Development.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003eAcknowledgements\u003c/p\u003e\n\u003cp\u003eThe authors acknowledge all the parents and children for their participation.Further, the authors are grateful to the staff of Bibliosalut, the Medical Balearic Library. We also appreciate the skilled voluntary help from the staff of La Vileta pediatric services.\u003c/p\u003e\n\u003cp\u003eAuthors\u0026rsquo; contributions\u003c/p\u003e\n\u003cp\u003eAF and ES had full access to all the data in the study and take responsibility for the integrity of the data. Study concept and design: MM and SV. Acquisition, analysis, or interpretation of data: AF and ES. Literature review and drafting of the manuscript: AT, IP and SV. All authors approved the final manuscript for submission.\u003c/p\u003e\n\u003cp\u003eFunding\u003c/p\u003e\n\u003cp\u003eUnfunded research. No competing financial interests exist for the authors.\u003c/p\u003e\n\u003cp\u003eAvailability of data and materials\u003c/p\u003e\n\u003cp\u003eThe datasets generated and/or analysed during the current study are not publicly available since patients could be identified by knowing their date of birth and date of attending the health service, but are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003eEthics approval and consent to participate\u003c/p\u003e\n\u003cp\u003eThe Manuscripts includes a statement on ethics approval and consent, it includes the name of the ethics committee that approved the study. The study\u0026apos;s protocol was reviewed and approved by the Balearic institutional review board for Health and Medical Research (ECIAP-2023).\u003c/p\u003e\n\u003cp\u003eConsent for publication\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003eCompeting interests\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eDhaun N, McAdoo SP. The changing role of glucocorticoids in the treatment of anti-neutrophil cytoplasmic antibody-associated vasculitis. Kidney Int. 2022;101(2):201-204. httpsdoi: 10.1016/j.kint.2021.11.006. PMID: 35065686.\u003c/li\u003e\n \u003cli\u003eBalart MT, Russell L, Narula N, Bajaj G, Chauhan U, et al. Declining Use of Corticosteroids for Crohn\u0026apos;s Disease Has Implications for Study Recruitment: Results of a Pilot Randomized Controlled Trial. J Can Assoc Gastroenterol. 2020;4(5):214-221. https://doi:10.1093/jcag/gwaa037\u003c/li\u003e\n \u003cli\u003eHaughney J, Winders T, Holmes S, Chanez P, Menzies-Gow A, et al. A Charter to Fundamentally Change the Role of Oral Corticosteroids in the Management of Asthma. Adv Ther. 2023;40(6):2577-2594. https://doi: 10.1007/s12325-023-02479-0.\u003c/li\u003e\n \u003cli\u003eYates RW, Doull IJ. A risk-benefit assessment of corticosteroids in the management of croup. Drug Saf. 1997;16(1):48-55. https://doi:10.2165/00002018-199716010-00003\u003c/li\u003e\n \u003cli\u003eAljebab F, Choonara I, Conroy S. Systematic review of the toxicity of short-course oral corticosteroids in children. Arch Dis Child. 2016;101(4):365-70. https://doi: 10.1136/archdischild-2015-309522.\u003c/li\u003e\n \u003cli\u003eFernandes RM, Wingert A, Vandermeer B, Featherstone R, Ali S, Plint AC, Stang AS, Rowe BH, Johnson DW, Allain D, Klassen TP, Hartling L. Safety of corticosteroids in young children with acute respiratory conditions: a systematic review and meta-analysis. BMJ Open. 2019 ;9(8):e028511. https://doi: 10.1136/bmjopen-2018-028511.\u003c/li\u003e\n \u003cli\u003eYao TC, Wang JY, Chang SM, Chang YC, Tsai YF, et al. Association of Oral Corticosteroid Bursts With Severe Adverse Events in Children. JAMA Pediatr. 2021;175(7):723-729. https://doi: 10.1001/jamapediatrics.2021.0433.\u003c/li\u003e\n \u003cli\u003eDuijts L, Ramadhani MK, Moll HA. Breastfeeding protects against infectious diseases during infancy in industrialized countries. A systematic review. Matern Child Nutr. 2009;5(3):199\u0026ndash;210. https://doi.org/10.1111/j.1740-8709.2008.00176.x.\u003c/li\u003e\n \u003cli\u003eLi R, Dee D, Li CM, Hoffman HJ, Grummer-Strawn LM, et al. Breastfeeding and risk of infections at 6 years. Pediatrics. 2014;134(Suppl 1):S13\u0026ndash;20. https://doi.org/10.1542/peds.2014-0646D.\u003c/li\u003e\n \u003cli\u003eWilson AC, Forsyth JS, Greene SA, Irvine L, Hau C, Howie PW. Relation of infant diet to childhood health: seven year follow up of cohort of children in Dundee infant feeding study. BMJ. 1998;316(7124):21\u0026ndash;5. https://doi.org/10.1136/bmj.316.7124.21.\u003c/li\u003e\n \u003cli\u003eCosta JA, Rodriguez-Trabal C, Pareja I, Tur A, Mambie M, et al. P-Wave Axis of Schoolchildren Who Were Once Breastfed. Children (Basel). 2023;10(7):1255. https://doi:10.3390/children10071255\u003c/li\u003e\n \u003cli\u003eChu EK, Drazen JM. Asthma: one hundred years of treatment and onward. Am J Respir Crit Care Med. 2005;171(11):1202-8. https://doi: 10.1164/rccm.200502-257OE.\u003c/li\u003e\n \u003cli\u003eMaspero JF, Cruz AA, Beltran CFP, Ali Munive A, Montero-Arias F, et al. The use of systemic corticosteroids in asthma management in Latin American countries. World Allergy Organ J. 2023;16(4):100760. https://doi:10.1016/j.waojou.2023.100760\u003c/li\u003e\n \u003cli\u003eCameron SJ, Cooper EJ, Crompton GK, Hoare MV, Grant IW. Substitution of beclomethasone aerosol for oral prednisolone in the treatment of chronic asthma. Br Med J. 1973;4(5886):205-7. https://doi: 10.1136/bmj.4.5886.205.\u003c/li\u003e\n \u003cli\u003eAregbesola A, Tam CM, Kothari A, Le M-L, Ragheb M, Klassen TP. Glucocorticoids for croup in children. Cochrane Database of Systematic Reviews. 2023;1: CD001955. https://doi: 10.1002/14651858.CD001955.pub5\u003c/li\u003e\n \u003cli\u003eCollins AD, Beigelman A. An update on the efficacy of oral corticosteroids in the treatment of wheezing episodes in preschool children. Ther Adv Respir Dis. 2014;8:182\u0026ndash;190.\u003c/li\u003e\n \u003cli\u003eBourdin A, Adcock I, Berger P, Bonniaud P, Chanson P, et al. How can we minimise the use of regular oral corticosteroids in asthma? Eur Respir Rev. 2020;29(155):190085. https://doi: 10.1183/16000617.0085-2019.\u003c/li\u003e\n \u003cli\u003eSeo Y, Ahn T, Paik J, Kang S. Should steroids be used for anaphylaxis after the COVID-19 vaccine?. Clin Exp Emerg Med. 2021;8(4):251-254. https://doi:10.15441/ceem.21.087\u003c/li\u003e\n \u003cli\u003eAmrol DJ. Risks associated with steroid bursts in children. NEJM Watch 2021, https://www.jwatch.org/na53505/2021/04/29/risks-associated-with-steroid-bursts-children (last time accessed, 5\u003csup\u003eth\u003c/sup\u003e August, 2024).\u003c/li\u003e\n \u003cli\u003eTaine M, Offredo L, Weill A, Dray-Spira R, Zureik M, Chalumeau M. Pediatric Outpatient Prescriptions in Countries With Advanced Economies in the 21st Century: A Systematic Review. JAMA Netw Open. 2022;5(4):e225964. https://doi: 10.1001/jamanetworkopen.2022.5964.\u003c/li\u003e\n \u003cli\u003eFrank NM, Lynch KF, Uusitalo U, Yang J, L\u0026ouml;nnrot M, et al. The relationship between breastfeeding and reported respiratory and gastrointestinal infection rates in young children. BMC Pediatr. 2019;19(1):339. https://doi:10.1186/s12887-019-1693-2\u003c/li\u003e\n \u003cli\u003eBloch AM., Mimouni D, Mimouni M, Gdalevich M. Does breastfeeding protect against allergic rhinitis during childhood? A meta-analysis of prospective studies. Acta Paediatr. 2002;91:275\u0026ndash;279. https://doi:10.1111/j.1651-2227.2002.tb01714.x.\u003c/li\u003e\n \u003cli\u003eLodge CJ, Tan DJ, Lau MX, Dai X, Tham R, et al. Breastfeeding and asthma and allergies: A systematic review and meta-analysis. Acta Paediatr. 2015;104:38\u0026ndash;53. https://doi:10.1111/apa.13132.\u003c/li\u003e\n \u003cli\u003eDuffy LC, Faden H, Wasielewski R, Wolf J, Krystofik D. Tonawanda/Williamsville pediatrics. Exclusive breastfeeding protects against bacterial colonization and day care exposure to otitis media. Pediatrics. 1997;100(4):E7.\u003c/li\u003e\n \u003cli\u003eFroom J, Culpepper L, Green LA, de Melker RA, Grob P, et al.. A cross-national study of acute otitis media: risk factors, severity, andtreatment at initial visit. Report from the international primary care network (IPCN) and the ambulatory sentinel practice network (ASPN). J Am Board Fam Pract. 2001;14(6):406\u0026ndash;17.\u003c/li\u003e\n \u003cli\u003eMiliku K, Azad MB. Breastfeeding and the Developmental Origins of Asthma: Current Evidence, Possible Mechanisms, and Future Research Priorities. Nutrients. 2018;10(8):995. https://doi: 10.3390/nu10080995.\u003c/li\u003e\n \u003cli\u003eGreer FR, Sicherer SH, Burks AW; COMMITTEE ON NUTRITION; SECTION ON ALLERGY AND IMMUNOLOGY. The Effects of Early Nutritional Interventions on the Development of Atopic Disease in Infants and Children: The Role of Maternal Dietary Restriction, Breastfeeding, Hydrolyzed Formulas, and Timing of Introduction of Allergenic Complementary Foods. Pediatrics. 2019;143(4):e20190281. https://doi: 10.1542/peds.2019-0281.\u003c/li\u003e\n \u003cli\u003eBarker, D.J. The fetal and infant origins of adult disease. BMJ 1990, 301, 1111.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTable 1 \u0026nbsp;Demographic and somatometric data by mixed breastfeeding duration. Data are mean (SD) unless otherwise specified.\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"18.351477449455675%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eVARIABLE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.97045101088647%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eGroup 1, cut-off at 90 days\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.087091757387247%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.65940902021773%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eGroup 2, cut-off at 180 days\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.9315707620528775%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"21.714285714285715%\" valign=\"top\"\u003e\n \u003cp\u003eBf \u0026lt; 90 days\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.666666666666668%\" valign=\"top\"\u003e\n \u003cp\u003eBf =\u0026gt; 90 days\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.904761904761905%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.61904761904762%\" valign=\"top\"\u003e\n \u003cp\u003eBf \u0026lt; 180 days\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.38095238095238%\" valign=\"top\"\u003e\n \u003cp\u003eBf =\u0026gt; 180 days\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.714285714285714%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"18.351477449455675%\" valign=\"top\"\u003e\n \u003cp\u003eAge (years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.729393468118197%\" valign=\"top\"\u003e\n \u003cp\u003e11.04 (3.16)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.241057542768274%\" valign=\"top\"\u003e\n \u003cp\u003e11.26 (3.02)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.087091757387247%\" valign=\"top\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.018662519440124%\" valign=\"top\"\u003e\n \u003cp\u003e11.12 (3.08)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.640746500777606%\" valign=\"top\"\u003e\n \u003cp\u003e11.20 (3.15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.9315707620528775%\" valign=\"top\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"18.351477449455675%\" valign=\"top\"\u003e\n \u003cp\u003eGirls//boys\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.729393468118197%\" valign=\"top\"\u003e\n \u003cp\u003e26//27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.241057542768274%\" valign=\"top\"\u003e\n \u003cp\u003e21//22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.087091757387247%\" valign=\"top\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.018662519440124%\" valign=\"top\"\u003e\n \u003cp\u003e36//37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.640746500777606%\" valign=\"top\"\u003e\n \u003cp\u003e10//12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.9315707620528775%\" valign=\"top\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"18.351477449455675%\" valign=\"top\"\u003e\n \u003cp\u003eWeight percentile\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.729393468118197%\" valign=\"top\"\u003e\n \u003cp\u003e53.24 (28.36)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.241057542768274%\" valign=\"top\"\u003e\n \u003cp\u003e56.81 (26.57)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.087091757387247%\" valign=\"top\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.018662519440124%\" valign=\"top\"\u003e\n \u003cp\u003e54.75 (27.62)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.640746500777606%\" valign=\"top\"\u003e\n \u003cp\u003e55.19 (27.62)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.9315707620528775%\" valign=\"top\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"18.351477449455675%\" valign=\"top\"\u003e\n \u003cp\u003eHeight percentile\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.729393468118197%\" valign=\"top\"\u003e\n \u003cp\u003e64.17 (25.97)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.241057542768274%\" valign=\"top\"\u003e\n \u003cp\u003e64.60 (25.95)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.087091757387247%\" valign=\"top\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.018662519440124%\" valign=\"top\"\u003e\n \u003cp\u003e64.88 (25.39)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.640746500777606%\" valign=\"top\"\u003e\n \u003cp\u003e64.60 (25.95)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.9315707620528775%\" valign=\"top\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"18.351477449455675%\" valign=\"top\"\u003e\n \u003cp\u003eBMI percentile\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.729393468118197%\" valign=\"top\"\u003e\n \u003cp\u003e47.32 (28.50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.241057542768274%\" valign=\"top\"\u003e\n \u003cp\u003e48.26 (26.12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.087091757387247%\" valign=\"top\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.018662519440124%\" valign=\"top\"\u003e\n \u003cp\u003e48.49 (28.31)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.640746500777606%\" valign=\"top\"\u003e\n \u003cp\u003e45.24 (24.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.9315707620528775%\" valign=\"top\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;ABBREVIATIONS: Bf, mixed breastfeeding; BMI, body mass index; NS, non significant.\u003c/p\u003e\n\u003cp\u003eTable 2. Glucocorticoid courses in schoolchildren who have been breastfed up to or beyond the age of 90 days.\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"41.21306376360809%\" valign=\"top\"\u003e\n \u003cp\u003eVARIABLE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.55054432348367%\" valign=\"top\"\u003e\n \u003cp\u003eMixed breastfeeding \u0026lt; 90 days\u003c/p\u003e\n \u003cp\u003emean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.3950233281493%\" valign=\"top\"\u003e\n \u003cp\u003eMixed breastfeeding =\u0026gt; 90 days\u003c/p\u003e\n \u003cp\u003emean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.841368584758943%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"41.21306376360809%\" valign=\"top\"\u003e\n \u003cp\u003eTotal number of days on GC treatment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.55054432348367%\" valign=\"top\"\u003e\n \u003cp\u003e7.85 (14,81)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.3950233281493%\" valign=\"top\"\u003e\n \u003cp\u003e2.77 (3.91)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.841368584758943%\" valign=\"top\"\u003e\n \u003cp\u003e0.031*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"41.21306376360809%\" valign=\"top\"\u003e\n \u003cp\u003eTotal number of GC courses\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.55054432348367%\" valign=\"top\"\u003e\n \u003cp\u003e2.12 (3,29)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.3950233281493%\" valign=\"top\"\u003e\n \u003cp\u003e0.77 (1.13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.841368584758943%\" valign=\"top\"\u003e\n \u003cp\u003e0.012*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"41.21306376360809%\" valign=\"top\"\u003e\n \u003cp\u003eGC courses for acute bronchitis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.55054432348367%\" valign=\"top\"\u003e\n \u003cp\u003e0.92 (2,40)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.3950233281493%\" valign=\"top\"\u003e\n \u003cp\u003e0.37 (0.85)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.841368584758943%\" valign=\"top\"\u003e\n \u003cp\u003e0.16\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"41.21306376360809%\" valign=\"top\"\u003e\n \u003cp\u003eGC courses for acute laringitis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.55054432348367%\" valign=\"top\"\u003e\n \u003cp\u003e0.81 (1,92)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.3950233281493%\" valign=\"top\"\u003e\n \u003cp\u003e0.16 (0.57)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.841368584758943%\" valign=\"top\"\u003e\n \u003cp\u003e0.036*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"41.21306376360809%\" valign=\"top\"\u003e\n \u003cp\u003eGC courses for rash\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.55054432348367%\" valign=\"top\"\u003e\n \u003cp\u003e0.21 (0,46)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.3950233281493%\" valign=\"top\"\u003e\n \u003cp\u003e0.07 (0.26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.841368584758943%\" valign=\"top\"\u003e\n \u003cp\u003e0.07\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"41.21306376360809%\" valign=\"top\"\u003e\n \u003cp\u003eMixed breastfeeding duration\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.55054432348367%\" valign=\"top\"\u003e\n \u003cp\u003e10.19 (18.19)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.3950233281493%\" valign=\"top\"\u003e\n \u003cp\u003e167.91 (56.83)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.841368584758943%\" valign=\"top\"\u003e\n \u003cp\u003e0.0001****\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;Significance derived from \u003cem\u003et\u003c/em\u003e test of means.\u003c/p\u003e\n\u003cp\u003eABBREVIATIONS: *\u0026lt;=0.05; ****\u0026lt;=0.0001; GC, Glucocorticoids; SD, standard deviation.\u003c/p\u003e\n\u003cp\u003eTable 3. Glucocorticoid courses in schoolchildren who have been breastfed up to or beyond the age of 180 days.\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"41.21306376360809%\" valign=\"top\"\u003e\n \u003cp\u003eVARIABLE\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.55054432348367%\" valign=\"top\"\u003e\n \u003cp\u003eMixed breastfeeding \u0026lt; 180 days\u003c/p\u003e\n \u003cp\u003emean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.3950233281493%\" valign=\"top\"\u003e\n \u003cp\u003eMixed breastfeeding =\u0026gt; 180 days\u003c/p\u003e\n \u003cp\u003emean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.841368584758943%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"41.21306376360809%\" valign=\"top\"\u003e\n \u003cp\u003eTotal number of days on GC treatment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.55054432348367%\" valign=\"top\"\u003e\n \u003cp\u003e6.68 (12.82)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.3950233281493%\" valign=\"top\"\u003e\n \u003cp\u003e1.77 (2.96)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.841368584758943%\" valign=\"top\"\u003e\n \u003cp\u003e0.08\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"41.21306376360809%\" valign=\"top\"\u003e\n \u003cp\u003eTotal number of GC courses\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.55054432348367%\" valign=\"top\"\u003e\n \u003cp\u003e1.82 (2.90)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.3950233281493%\" valign=\"top\"\u003e\n \u003cp\u003e0.45 (0.80)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.841368584758943%\" valign=\"top\"\u003e\n \u003cp\u003e0,03*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"41.21306376360809%\" valign=\"top\"\u003e\n \u003cp\u003eGC courses for acute bronchitis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.55054432348367%\" valign=\"top\"\u003e\n \u003cp\u003e0.81 (2.09)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.3950233281493%\" valign=\"top\"\u003e\n \u003cp\u003e0.23 (0.69)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.841368584758943%\" valign=\"top\"\u003e\n \u003cp\u003e0.21\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"41.21306376360809%\" valign=\"top\"\u003e\n \u003cp\u003eGC courses for acute laringitis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.55054432348367%\" valign=\"top\"\u003e\n \u003cp\u003e0.66 (1.69)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.3950233281493%\" valign=\"top\"\u003e\n \u003cp\u003e0.05 (0.21)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.841368584758943%\" valign=\"top\"\u003e\n \u003cp\u003e0.09\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"41.21306376360809%\" valign=\"top\"\u003e\n \u003cp\u003eGC courses for rash\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.55054432348367%\" valign=\"top\"\u003e\n \u003cp\u003e0.16 (0.41)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.3950233281493%\" valign=\"top\"\u003e\n \u003cp\u003e0.09 (0.29)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.841368584758943%\" valign=\"top\"\u003e\n \u003cp\u003e0.44\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"41.21306376360809%\" valign=\"top\"\u003e\n \u003cp\u003eMixed breastfeeding duration\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.55054432348367%\" valign=\"top\"\u003e\n \u003cp\u003e42.00 (54.17)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.3950233281493%\" valign=\"top\"\u003e\n \u003cp\u003e212.91 (39.57)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.841368584758943%\" valign=\"top\"\u003e\n \u003cp\u003e0.0001****\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eSignificance derived from \u003cem\u003et\u003c/em\u003e test of means.\u003c/p\u003e\n\u003cp\u003eABBREVIATIONS: **** \u0026lt;=0.0001; GC, Glucocorticoids; SD, standard deviation.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Breastfeeding, Asthma, Laryngitis, Exanthema, Glucocorticoids, Iatrogenic disease.","lastPublishedDoi":"10.21203/rs.3.rs-4869699/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4869699/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e There is mounting evidence on the harmful effects of glucocorticoid bursts prescribed to manage pediatric allergies or respiratory diseases. Therefore, minimizing glucocorticoid use in children deserves all possible support. Given that breastfeeding prevents infectious diseases and inflammation in children several years after the cessation of breastfeeding, we aimed to explore whether breastfeeding also prevents the prescription of glucocorticoids that occurs in these diseases.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethod:\u003c/strong\u003e This was a cross-sectional observational study in a primary care center of children who attended the well-child clinic at the beginning and end of primary school. Data on glucocorticoid prescription and information on breastfeeding duration were taken from these patients' medical files.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e We recruited 95 children with accurate data on glucocorticoid prescriptions and breastfeeding duration. At least one burst of glucocorticoids was prescribed to 47% of schoolchildren. The median time to the first dose of glucocorticoids from birth was three years (IQR, 2-4 y.). Breastfeeding duration below three months was coupled with approximately three times as many days (7.85 vs. 2.77; P=0.031) and three times as many bursts (2.12 versus 0.77; P=0.012) of glucocorticoids compared to breastfeeding beyond three months.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e Previous studies have reported the reduction of acute illnesses that may or may not require glucocorticoids among previously breastfed children. Our study took a step further to report the reduction of glucocorticoid bursts among children who were breastfed beyond three months of age. If future studies confirm the results presented at this preliminary stage, the goal of limiting glucocorticoid bursts in ambulatory Paediatrics may be easier to achieve in previously breastfed children.\u003c/p\u003e","manuscriptTitle":"It is not unusual to prescribe glucocorticoids to school children who were mostly formula- fed","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-09-06 03:34:43","doi":"10.21203/rs.3.rs-4869699/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"a4cc4a11-d1f5-435f-b00b-2cfd6c44561b","owner":[],"postedDate":"September 6th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-03-29T02:53:17+00:00","versionOfRecord":[],"versionCreatedAt":"2024-09-06 03:34:43","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4869699","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4869699","identity":"rs-4869699","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}