Gudnadottir Unnur, Fransson Emma, Ljungman Gustaf, Wikman Anna, Vlieghe Erika, Engstrand Lars, Brusselaers Nele
Department of Microbiology, Tumour and Cell Biology (MTC), Centre for Translational Microbiome Research, Karolinska Institutet, Tomtebodavägen 16, Solna, 171 65, Stockholm, Sweden.
Department of Women's and Children's health, Uppsala University, Sjukhusvägen 7, 753 09, Uppsala, Sweden.
Drug Saf. 2025 Apr;48(4):375-388. doi: 10.1007/s40264-024-01500-x. Epub 2024 Dec 12.
Our microbiome is established during infancy, a time important for later health and long-term effects. Proton pump inhibitors and antibiotics are regularly prescribed during pregnancy. Both drugs cause microbiome disturbance and have been associated with increased cancer risk in adults, but effects of these drugs on the growing foetus and infant remain understudied.
The aim of this study is to study the association between prenatal and early life proton pump inhibitor and antibiotics exposure and the risk of childhood cancer.
This study is a retrospective population-based cohort design, using registry data on all births (n = 722,372) in Sweden between 2006 and 2016, according to the STROBE checklist. For women who had multiple children in the timeframe of the study, only the first child during the time period was included in the cohort. Exposure was defined as either ≥ 1 proton pump inhibitor or antibiotics prescription during pregnancy, or during the first 2 years of life. Outcome was defined as cancer at any time during the follow-up or cancer after the age of 2 years for early life exposure. Multivariable Cox proportional hazard models were used to calculate hazard ratios.
In total, 1091 (0.2%) children were diagnosed with malignant cancer during the follow-up. Prenatal exposure to proton pump inhibitors and antibiotics were not associated with an increased risk of cancer. Regarding early life exposure, proton pump inhibitors were associated with an increased risk of cancer at age two or older (adjusted hazard ratio [aHR] 3.68, 95% confidence interval [CI] 2.24-6.06).
We did not find evidence that prenatal proton pump inhibitors and antibiotics were associated with overall childhood cancer. However, proton pump inhibitors during early life were associated with an increased risk of childhood cancer, but indication on drug use was not available and confounding by indication may be present.
我们的微生物群在婴儿期形成，这一时期对日后的健康和长期影响至关重要。质子泵抑制剂和抗生素在孕期经常被使用。这两种药物都会导致微生物群紊乱，且与成年人患癌风险增加有关，但这些药物对发育中的胎儿和婴儿的影响仍未得到充分研究。
本研究旨在探讨产前及生命早期接触质子泵抑制剂和抗生素与儿童癌症风险之间的关联。
本研究采用基于人群的回顾性队列设计，根据STROBE清单，使用瑞典2006年至2016年间所有出生记录（n = 722,372）的数据。对于在研究期间生育多个孩子的女性，队列中仅纳入该时间段内的第一个孩子。暴露定义为孕期或生命的前两年内至少有1次质子泵抑制剂或抗生素处方。结局定义为随访期间任何时间的癌症，或生命早期暴露情况下2岁以后的癌症。使用多变量Cox比例风险模型计算风险比。
在随访期间，共有1091名（0.2%）儿童被诊断患有恶性癌症。产前接触质子泵抑制剂和抗生素与癌症风险增加无关。关于生命早期暴露，质子泵抑制剂与2岁及以上儿童患癌风险增加有关（调整后风险比[aHR] 3.68，95%置信区间[CI] 2.24 - 6.06）。
我们没有发现证据表明产前质子泵抑制剂和抗生素与儿童总体癌症有关。然而，生命早期使用质子泵抑制剂与儿童癌症风险增加有关，但用药指征不明，可能存在指征性混杂因素。
