Department of Urology and Pediatrics, University of Iowa Hospitals and Clinics, 200 Hawkins Drive, 3RCP, Iowa City, IA, 52242-1089, USA.
Department of Urology, Yale University, 789 Howard Avenue, New Haven, CT, 06520-8234, USA.
J Pediatr Urol. 2018 Aug;14(4):325.e1-325.e7. doi: 10.1016/j.jpurol.2018.07.007. Epub 2018 Jul 23.
Continuous antibiotic prophylaxis (CAP) is a mainstay of treatment for children with vesicoureteral reflux (VUR). There has been an increasing focus on the effect of antibiotics on gut microbiota and subsequent repercussions on growth. Continuous antibiotic prophylaxis is generally considered safe; however, its impact on growth in children with VUR remains unknown.
This objective of this study was to determine whether CAP altered height, weight, or body mass index (BMI) in children with VUR.
Children diagnosed with primary VUR were identified. Demographics including weight and height percentiles, BMI and BMI percentiles, age, gender, antibiotic class, prior antibiotic use, urinary tract infection history, and breakthrough infections were tested in univariate and multivariate analyses. Primary outcome was change in BMI as well as weight, height, and BMI percentiles.
One hundred eighty patients (146 girls, 34 boys) were prescribed CAP at mean age of 29.2 ± 26.2 months. Mean follow-up on CAP was 4.1 ± 3.3 years, with median follow-up of 3.08 years. Mean increase in weight percentile was 1.49 (2.02 males, 1.37 females; P = 0.46). Mean decrease in height percentile was -4.44 (-2.18 males, -4.95 females; P = 0.51). Age at diagnosis (P = 0.004) and history of prior treatment courses of antibiotics (P = 0.007) were associated with a significant BMI increase (Fig. 1). Body mass index percentile increased from 58.4 to 66.5; however, this increase was only significant in children aged above 1 year (P < 0.0001). Of note, children above 1 year of age were significantly more likely to have a history of prior treatment courses of antibiotics (58% vs 32%; P < 0.0001), and when controlling for prior antibiotic use, the increase in BMI percentile in those over 1 year of age did not reach significance.
The use of antibiotics has been associated with alterations in pediatric growth parameters in both animal models and clinical studies. However, little information exists on the impact of prophylactic-dosed antibiotics on growth. While this study is limited by the retrospective analysis and small sample size, it was found that the use of CAP did impact growth parameters, with a stronger effect seen in children who had received prior treatment courses of antibiotics before the infection leading to the initiation of CAP.
Continuous antibiotic prophylaxis was correlated with significant increase in BMI in children with prior antibiotic usage and a significant increase in BMI percentile in children aged above 1 year. Continuous antibiotic prophylaxis was also associated with decreased height percentiles, particularly in patients aged less than 1 year, though it did not reach statistical significance. Further analysis is needed to investigate whether these effects on weight, height, and BMI are persistent and clinically significant.
持续性抗生素预防治疗（CAP）是治疗小儿膀胱输尿管反流（VUR）的主要方法。人们越来越关注抗生素对肠道微生物群的影响，以及随后对生长的影响。一般认为持续性抗生素预防治疗是安全的；然而，其对 VUR 患儿生长的影响尚不清楚。
本研究旨在确定 CAP 是否改变了 VUR 患儿的身高、体重或体重指数（BMI）。
确定了被诊断为原发性 VUR 的患儿。在单变量和多变量分析中，对体重和身高百分位数、BMI 和 BMI 百分位数、年龄、性别、抗生素类别、既往抗生素使用、尿路感染史和突破性感染等进行了测试。主要结局是 BMI 以及体重、身高和 BMI 百分位数的变化。
180 名患儿（146 名女孩，34 名男孩）在平均年龄 29.2±26.2 个月时接受 CAP 治疗。CAP 的平均随访时间为 4.1±3.3 年，中位随访时间为 3.08 年。体重百分位数平均增加 1.49（男性 2.02，女性 1.37；P=0.46）。身高百分位数平均下降 4.44（男性 2.18，女性 4.95；P=0.51）。诊断时的年龄（P=0.004）和既往抗生素治疗疗程的历史（P=0.007）与 BMI 的显著增加有关（图 1）。BMI 百分位数从 58.4 增加到 66.5；然而，这一增加仅在 1 岁以上的儿童中具有统计学意义（P<0.0001）。值得注意的是，1 岁以上的儿童更有可能有既往抗生素治疗疗程的病史（58%比 32%；P<0.0001），并且当控制既往抗生素使用时，1 岁以上儿童 BMI 百分位数的增加没有达到统计学意义。
抗生素的使用已在动物模型和临床研究中与儿科生长参数的改变有关。然而，关于预防性剂量的抗生素对生长的影响，信息很少。虽然这项研究受到回顾性分析和样本量小的限制，但发现 CAP 的使用确实影响了生长参数，在感染导致 CAP 开始之前接受过既往抗生素治疗疗程的儿童中，这种影响更强。
在有既往抗生素使用史的儿童中，持续性抗生素预防治疗与 BMI 的显著增加相关，在 1 岁以上的儿童中，BMI 百分位数有显著增加。持续性抗生素预防治疗也与身高百分位数下降有关，尤其是在年龄小于 1 岁的患者中，但未达到统计学意义。需要进一步分析这些对体重、身高和 BMI 的影响是否持续且具有临床意义。
