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Formula feeding increases the risk of antibiotic prescriptions in children up to 2 years: results from a cohort study

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Abstract

Association between the use of infant formula and risks for infants’ health is seldom studied in western countries. We set up a historical cohort based on record linkage analysis, combining the data from administrative databases providing individual data. Infants receiving the second dose of pediatric immunization between 2015 and 2017 were included. The main outcome measure was antibiotic prescriptions from enrolment up to 24 months of age, by infant feeding category at enrolment. The extended Cox regression technique was used to account for recurrent events. The infants’ cohort included 40,258 5-month-old infants; during the study period, 60,932 antibiotic prescriptions were filled. Compared with infants fully breastfed, children fed with both maternal milk and formula received 106 more antibiotic prescriptions per 1000 children/year, whereas infants receiving formula only had 138 excess prescriptions per 1000 children/year. The association with infant feeding was statistically significant and remained unchanged after adjustment for common confounders (adjusted hazard ratio, HR, for complementary feeding vs full breastfeeding 1.09; 95%CI 1.05 to 1.12; formula only versus full breastfeeding adj. HR 1.12; 95%CI 1.08 to 1.16).

Conclusion: In our cohort, we observed a positive association between infant formula use considered a proxy of infections antibiotic prescription rate, considered a proxy of infections. The association followed a gradient.

What is Known:

• Formula feeding is associated with increased morbidity and mortality even in western countries, but still, it is common.

• Information on formula are seldom unbiased; thus, public perception of risks is distorted.

What is New:

• In a large Italian cohort of infants, formula feeding at 5 months of age results to be associated with an increased rate of antibiotic prescription (considered to be a proxy of infection) up to 24 months of age: the association follows a dose-response relationship.

• Record linkage analysis using administrative databases provides useful information at a limited cost.

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Abbreviations

BF:

Breastfeeding

BMI:

Body mass index

DRG:

Diagnosis-related group

95%CI:

95% confidence interval

HR:

Hazard ratio

ICD-IX:

International Classification of Diseases, 9th edition

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Acknowledgments

The authors wish to thank Bruna Borgini (biologist), Michela Bragliani (biologist), and Elena Castelli (biologist) (Emilia-Romagna region) for administrative support at regional level; APEC (Association of Community Pediatricians) for conceiving and sustaining the monitoring system since 1999. Finally, the authors are sincerely grateful to all parents and caregivers who participated to the survey for providing infant feeding information. The authors also thank the following members of the Regional breastfeeding monitoring group (2015-2017): Cristina Barella (MD), Angela Castellana (nurse), Carla Ghigini (nurse), Roberto Maffi (nurse), Ilario Maffini (MD), Anna Maria Milani (MD), Raffaella Pellizzari (nurse), and Marilena Prazzoli (MD) (Piacenza AUSL); Giovanna Bussolati (MD), Icilio Dodi (MD), Emanuela Ferraroni (MD), and Nicoletta Piazza (MD) (Parma AUSL); Marina Sparano (midwife), Luigi Moscara (MD), and Alessandro Volta (MD) (Reggio Emilia AUSL); Giulio Sighinolfi (MD) and Maria Vezzani (MD) (Modena AUSL); Paola Lenzi (nurse) and Rita Ricci (MD) (Bologna AUSL); Barbara Baldisserri (nurse), Paola Caroli (MD), Lucia Suzzi (midwife), and Elisabetta Valenti (MD) (Imola AUSL); Massimo Cornale (MD), Chiara Cuoghi (MD), and Flavia Pascoletti (MD) (Ferrara AUSL); Luisa Baldi (nurse), Giovanna Cappelli (nurse), Oriana Gasperoni (midwife), Annarita Loreti (nurse), Giuliana Monti (MD), Claudia Muratori (MD), Norma Pelliconi (nurse), and Ivonne Zoffoli (MD) (ex Ravenna AUSL); Anna Maria Baldoni (MD) (ex Forlì AUSL); Antonella Brunelli (MD), Massimo Farneti (MD), Marcella Lombardi (midwife), and Fosca Marrone (MD) (ex Cesena AUSL); Maurizio Bigi (MD), Roberta Gabellini (nurse), Antonella Mazzocchi (midwife), and Morena Vanni (nurse) (ex Rimini AUSL).

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Authors and Affiliations

  1. SaPeRiDoc-Documentation Centre on Perinatal and Reproductive Health, Primary Care Service, Regional Health Authority of Emilia-Romagna, viale Aldo Moro 21, 40127, Bologna, Italy

    Simona Di Mario & Vittorio Basevi

  2. Regional Health and Social Agency of Emilia-Romagna, viale Aldo Moro 21, 40127, Bologna, Italy

    Carlo Gagliotti & Rossella Buttazzi

  3. Primary Care Service, Regional Health Authority of Emilia-Romagna, viale Aldo Moro 21, 40127, Bologna, Italy

    Andrea Donatini, Silvana Borsari & Luca Barbieri

  4. Information Technology Service, Regional Health Authority of Emilia-Romagna, viale Aldo Moro 21, 40127, Bologna, Italy

    Sergio Battaglia

  5. Department of Medical and Surgical Sciences, Statistics Unit, University Hospital of Modena and Reggio Emilia, Modena, Italy

    Sara Balduzzi

Authors
  1. Simona Di Mario
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  2. Carlo Gagliotti
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  3. Andrea Donatini
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  4. Sergio Battaglia
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  5. Rossella Buttazzi
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  6. Sara Balduzzi
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  7. Silvana Borsari
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  8. Vittorio Basevi
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  9. Luca Barbieri
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Consortia

and the Regional breastfeeding monitoring group

  • Cristina Barella
  • , Angela Castellana
  • , Carla Ghigini
  • , Roberto Maffi
  • , Ilario Maffini
  • , Anna Maria Milani
  • , Raffaella Pellizzari
  • , Marilena Prazzoli
  • , Giovanna Bussolati
  • , Icilio Dodi
  • , Emanuela Ferraroni
  • , Nicoletta Piazza
  • , Marina Sparano
  • , Luigi Moscara
  • , Alessandro Volta
  • , Giulio Sighinolfi
  • , Maria Vezzani
  • , Paola Lenzi
  • , Rita Ricci
  • , Barbara Baldisserri
  • , Paola Caroli
  • , Lucia Suzzi
  • , Elisabetta Valenti
  • , Massimo Cornale
  • , Chiara Cuoghi
  • , Flavia Pascoletti
  • , Luisa Baldi
  • , Giovanna Cappelli
  • , Oriana Gasperoni
  • , Annarita Loreti
  • , Giuliana Monti
  • , Claudia Muratori
  • , Norma Pelliconi
  • , Ivonne Zoffoli
  • , Anna Maria Baldoni
  • , Antonella Brunelli
  • , Massimo Farneti
  • , Marcella Lombardi
  • , Fosca Marrone
  • , Maurizio Bigi
  • , Roberta Gabellini
  • , Antonella Mazzocchi
  •  & Morena Vanni

Contributions

Simona Di Mario conceived the idea to carry out the record linkage analysis, designed the study, wrote the first draft of the paper, and submitted it to the journal; Carlo Gagliotti developed the analysis plan and run it; Andrea Donatini supported the study design and performed the record linkage; Sergio Battaglia supported the study design and performed the record linkage; Rossella Buttazzi extracted and analyzed the data; Sara Balduzzi supported and checked the data analysis; Silvana Borsari supervised and coordinated the research team; Vittorio Basevi performed the literature search for background information; Luca Barbieri supervised and coordinated the research team. All the authors revised and approved the final version of the manuscript.

Corresponding author

Correspondence to Simona Di Mario.

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The authors declare that they have no conflict of interest.

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This article does not contain any studies with human participants or animals performed by any of the authors.

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Communicated by Mario Bianchetti

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Di Mario, S., Gagliotti, C., Donatini, A. et al. Formula feeding increases the risk of antibiotic prescriptions in children up to 2 years: results from a cohort study. Eur J Pediatr 178, 1867–1874 (2019). https://doi.org/10.1007/s00431-019-03462-0

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  • DOI: https://doi.org/10.1007/s00431-019-03462-0

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