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接受抗TNF抗体治疗的女性乳汁中肿瘤坏死因子(TNF)的减少。

Reduction of tumor necrosis factor (TNF) in milk of women receiving anti-TNF antibody.

作者信息

Sepiashvili Lusia, Brydon Avery, Koroshegyi Christine, Gold Anna, Dalvi Pooja, Ghayoori Sholeh, Rahman Mehzabin, Huang Vivian, Maxwell Cynthia, Nguyen Geoffrey C, Ito Shinya

机构信息

Department of Paediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, ON, Canada.

Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.

出版信息

Pediatr Res. 2025 May;97(6):1935-1942. doi: 10.1038/s41390-024-03672-9. Epub 2024 Nov 1.

Abstract

BACKGROUND

Tumor Necrosis Factor (TNF) are expressed in milk. Experimental data indicate enhanced brain growth and cognitive development in the mouse offspring given milk deficient in TNF and TNF-dependent chemokines. Although monoclonal antibodies against TNF (TNFmAb) are used during breastfeeding due to minimal milk excretion, whether it affects endogenous TNF levels in human milk is unclear.

METHODS

A prospective cohort study was conducted in 26 breastfeeding women with inflammatory bowel disease (IBD) and 31 non-IBD women. Milk TNF and related chemokines were measured at 5-6 weeks postpartum (early-lactation point) as a primary endpoint and further determined at 13-14 weeks postpartum. In a subset of their infants, neurocognitive development was assessed at 12 and 18 months of age using Bayley-III tool.

RESULTS

While milk TNF levels were not significantly different between the control and those with IBD, women with IBD receiving TNFmAb showed 70% lower median milk TNF than those without TNFmAb (P = 0.019) at early lactation period. TNF-dependent chemokines (MIP-1β and IP-10) also showed similar patterns. Neurocognitive development of the infants was not significantly different among the groups.

CONCLUSIONS

Women with IBD receiving TNFmAb show significantly lower milk TNF/chemokines at 5-6 weeks postpartum than those without TNFmAb.

CLINICALTRIALS

gov NCT03397108.

IMPACT

We found that milk concentrations of Tumor Necrosis Factor (TNF) and TNF-dependent chemokines (MIP-1β and IP-10) are low in women with inflammatory bowel disease who are receiving anti-TNF monoclonal antibody (TNFmAb), compared to those without concurrent anti TNF therapy. While maternal use of TNFmAb during breastfeeding is considered inconsequential to infant health due to their low levels of milk excretion, it affects profiles of endogenous cytokines in milk. Our findings provide a rationale to investigate human implications of the animal data in the literature that suggest enhancement of neurocognitive development of the offspring fed with milk deficient in TNF-dependent chemokines.

摘要

背景

肿瘤坏死因子(TNF)在母乳中表达。实验数据表明,给缺乏TNF和TNF依赖性趋化因子的小鼠后代喂食母乳后,其大脑生长和认知发育得到增强。尽管由于母乳中TNF排泄量极少,在母乳喂养期间会使用抗TNF单克隆抗体(TNFmAb),但尚不清楚它是否会影响人乳中的内源性TNF水平。

方法

对26名患有炎症性肠病(IBD)的哺乳期妇女和31名非IBD妇女进行了一项前瞻性队列研究。将产后5 - 6周(早期泌乳点)的母乳TNF及相关趋化因子作为主要终点进行测量,并在产后13 - 14周进一步测定。在她们的部分婴儿中,使用贝利婴幼儿发展量表第三版工具在12个月和18个月大时评估神经认知发育情况。

结果

虽然对照组和IBD患者的母乳TNF水平无显著差异,但在早期哺乳期,接受TNFmAb治疗的IBD妇女母乳中TNF的中位数比未接受TNFmAb治疗的妇女低70%(P = 0.019)。TNF依赖性趋化因子(MIP - 1β和IP - 10)也呈现出类似模式。各组婴儿的神经认知发育无显著差异。

结论

接受TNFmAb治疗的IBD妇女在产后5 - 6周时母乳中TNF/趋化因子水平显著低于未接受TNFmAb治疗的妇女。

临床试验

美国国立医学图书馆临床试验注册中心编号NCT03397108。

影响

我们发现,与未同时接受抗TNF治疗的妇女相比,接受抗TNF单克隆抗体(TNFmAb)治疗的炎症性肠病妇女母乳中肿瘤坏死因子(TNF)和TNF依赖性趋化因子(MIP - 1β和IP - 10)的浓度较低。虽然母乳喂养期间母亲使用TNFmAb因其在母乳中的排泄量低而被认为对婴儿健康影响不大,但它会影响母乳中内源性细胞因子的情况。我们的研究结果为研究文献中的动物数据对人类的影响提供了理论依据,这些数据表明,喂食缺乏TNF依赖性趋化因子的母乳可促进后代的神经认知发育。

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