Early exposures and inherent factors in premature newborns are associated with type 1 diabetes

Iren Zargari, Adi Adar, Iris Morag, Orit Pinhas-Hamiel, Ori Eyal, Rimona Keidar, Neta Loewenthal, Milana Levy, Orna Dally-Gottfried, Zohar Landau, Floris Levy-Khademi, Smadar Eventov-Friedman, David Zangen, Ilan Youngster, Marianna Rachmiel

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


Background: Pathophysiology of type 1 diabetes (T1D) involves immune responses that may be associated with early exposure to environmental factors among preterm newborns. The aim of this work was to evaluate for association between T1D and maternal, nutritional, and medical exposures during the neonatal period among premature newborns. Methods: This is a multicenter, matched case–control study. Preterm newborns, who developed T1D before 18 years, were matched by sex, gestational age (GA), birth date, and medical center of birth with newborns who did not develop TID. Data included maternal medical history, birth weight (BW), length of hospitalization, enteral and parenteral medications, fluid administration, and feeding modalities during hospitalization. Results: Fifty-two patients with T1D, 26 males, median age at T1D diagnosis 8.17 years (5.92–9.77), median GA 34 weeks (33-m36), and 132 matched controls, were included. Multivariate-conditional-regression demonstrated a significant association between T1D and any maternal illness (23.1% vs. 9.1%, OR = 4.99 (1.69–14.72), p = 0.004), higher BW-SDS (0.07 ± 0.95 vs. −0.27 ± 0.97, OR = 2.03 (1.19–3.49), p = 0.01), longer duration of glucose infusion (3 (1–5) days vs. 2 (0–4), OR = 1.23 (1.03–1.46), p = 0.02), and antibiotic therapy beyond the first week of life (19.2% vs. 6.9%, OR = 5.22 (1.32–20.70), p = 0.019). Antibiotic treatment during the first week of life was negatively associated with T1D (51.9% vs. 67.2%, OR 0.31 (0.11–0.88), p = 0.027). Conclusions: A novel association was demonstrated between the development of T1D and early interventions and exposures among preterm newborns. Impact: Type 1 diabetes mellitus during childhood may be associated with early exposures during the neonatal period, in addition to known maternal and neonatal metabolic parameters.Early exposure to intravenous antibiotics, differing between the first week of life and later, and longer parenteral glucose administration to preterm newborns were associated with childhood type 1 diabetes. This is in addition to familiar maternal risk factors.Future prospective studies should examine the microbial changes and immune system characteristics of preterm and term neonates exposed to parenteral antibiotics and glucose treatment, in order to validate our exploratory findings.

Original languageEnglish
Pages (from-to)1516-1522
Number of pages7
JournalPediatric Research
Issue number4
StatePublished - Oct 2023

Bibliographical note

Publisher Copyright:
© 2022, The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.


This work was funded by the HIPAK (The Israeli Society for Clinical Pediatrics) research grant, received by M.R. We would like to thank Dr. Ziv Tomer from the Department of Epidemiology and Preventive Medicine, School of Public Health, Tel Aviv University, for the statistical analysis.

FundersFunder number
Department of Epidemiology and Preventive Medicine, School of Public Health
Israeli Society for Clinical Pediatrics
Tel Aviv University


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