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早产儿的早期暴露和固有因素与 1 型糖尿病有关。

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

机构信息

Pediatric Endocrinology Unit, Division of Pediatrics, Shamir Medical Center (Assaf Harofeh), Zerifin, Israel.

Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.

出版信息

Pediatr Res. 2023 Oct;94(4):1516-1522. doi: 10.1038/s41390-022-02069-w. Epub 2022 Apr 29.

Abstract

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.

摘要

背景

1 型糖尿病(T1D)的病理生理学涉及免疫反应,这些反应可能与早产儿早期接触环境因素有关。本研究旨在评估新生儿期母体、营养和医疗暴露与早产儿 T1D 之间的关联。

方法

这是一项多中心、匹配的病例对照研究。在 18 岁之前发生 T1D 的早产儿,通过性别、胎龄(GA)、出生日期和出生医院与未发生 TID 的新生儿相匹配。数据包括母体病史、出生体重(BW)、住院时间、肠内和肠外药物、液体管理以及住院期间的喂养方式。

结果

本研究纳入了 52 例 T1D 患儿(男 26 例),T1D 诊断年龄中位数为 8.17 岁(5.92-9.77 岁),GA 中位数为 34 周(33-36 周),并匹配了 132 例对照患儿。多变量条件回归显示,T1D 与任何母体疾病(23.1% vs. 9.1%,OR=4.99(1.69-14.72),p=0.004)、较高的 BW-SDS(0.07±0.95 vs. -0.27±0.97,OR=2.03(1.19-3.49),p=0.01)、较长时间的葡萄糖输注(3(1-5)天 vs. 2(0-4)天,OR=1.23(1.03-1.46),p=0.02)和抗生素治疗超过第一周(19.2% vs. 6.9%,OR=5.22(1.32-20.70),p=0.019)有关。出生后第一周的抗生素治疗与 T1D 呈负相关(51.9% vs. 67.2%,OR 0.31(0.11-0.88),p=0.027)。

结论

本研究证明了早产儿在新生儿期的早期干预和暴露与 T1D 之间存在新的关联。

意义

儿童期 1 型糖尿病可能与新生儿期的早期暴露以及已知的母体和新生儿代谢参数有关。早期静脉内使用抗生素,在生命的第一周与后期不同,以及较长时间的静脉内葡萄糖给予早产儿,与儿童期 1 型糖尿病有关。这是除了常见的母体危险因素之外。未来的前瞻性研究应检查接受静脉内抗生素和葡萄糖治疗的早产儿和足月儿的微生物变化和免疫系统特征,以验证我们的探索性发现。

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