Incidence of kidney stones in pregnancy and associations with adverse obstetrical outcomes: a systematic review and meta-analysis of 4.7 million pregnancies

Renal stones are a common cause of non-obstetrical abdominal pain in pregnant women. Though the management of renal stones in pregnancy is challenging, it remains unclear how the incidence of kidney stones may affect the course of pregnancy and delivery. To determine the incidence of renal stones in pregnancy and its impact on adverse obstetrical outcomes. We conducted a systematic literature search of three databases: Ovid MEDLINE, Ovid EMBASE, and EBSCO CINAHL Plus. After the selection of articles, an additional hand-search of their citations was completed to maximize sensitivity. Databases were examined from the last four decades (19 March 1970) up to the search date (19 March 2020). Articles were excluded if they were not relevant to kidney stones or did not report outcomes related to pregnancy. Case reports, animal studies, and cadaveric studies were excluded. Conference abstracts, gray literature, and unpublished data were not eligible. All screening, extraction, and synthesis were completed in duplicate with two independent reviewers. All outcomes reported in the included studies were systematically evaluated to determine suitability for meta-analysis. Random-effects models and sensitivity analyses were used to account for interstudy variation. Renal stone incidence rates were pooled to generate summary proportions. Risk of bias assessment was completed using the Risk of Bias Assessment tool for Non-randomized Studies. Twenty-one studies were included through systematic review and approximately 4.7 million pregnancies across nine studies were included for meta-analysis. There are three major findings of this review regarding renal stone incidence in pregnancy and maternal, child, and birth-related outcomes associated with renal stones. First, we found pooled incidence of renal stones was 0.49%, or one case for every 204 pregnancies. Second, renal stones during pregnancy were significantly associated with the development of preeclampsia and urinary tract infection, as well as increased likelihood of low birth weight, preterm labor, and C-section deliveries. However, renal stones were not significantly associated with premature rupture of membranes or infant mortality. Third, there were limited obstetrical complications reported with either medical or surgical therapies although comparative outcomes were not provided in the majority of studies, precluding formal meta-analysis. Although renal stones in pregnancy are relatively rare, there may be an associated risk of serious adverse obstetrical outcomes. However, further research is required to understand whether these obstetrical outcomes are causal or due to other confounders. Interdisciplinary care and pregnancy-specific counseling should be advised for pregnant women with kidney stones.肾结石（renal stones）是妊娠期女性非产科腹痛的常见诱因。尽管妊娠期肾结石的临床管理颇具挑战，但目前尚不清楚肾结石的发病率会如何影响妊娠与分娩进程。为明确妊娠期肾结石的发病率及其对不良产科结局的影响，本研究针对Ovid MEDLINE、Ovid EMBASE及EBSCO CINAHL Plus三个数据库开展了系统性文献检索。在筛选文献后，研究团队还对纳入文献的参考文献进行了人工检索，以最大化检索灵敏度。检索范围涵盖过去四十年（1970年3月19日）至检索当日（2020年3月19日）的文献。若文献与肾结石无关或未报告妊娠相关结局，则予以排除；病例报告、动物实验及尸体研究均不在纳入范围内，会议摘要、灰色文献及未发表数据也不符合纳入标准。所有文献筛选、数据提取及结果整合均由两名独立审稿人以双人重复的方式完成。研究团队对纳入文献中报告的所有结局指标进行了系统性评估，以确定其是否适合纳入荟萃分析。采用随机效应模型与敏感性分析来处理研究间的异质性，合并肾结石发病率数据以得到汇总患病率。使用非随机研究偏倚风险评估工具（Risk of Bias Assessment tool for Non-randomized Studies）完成偏倚风险评价。本系统综述最终纳入21项研究，其中9项研究共涉及约470万例妊娠，被纳入荟萃分析。本综述针对妊娠期肾结石发病率及肾结石相关的母体、新生儿与分娩相关结局，得到三项主要结论：其一，合并后的肾结石发病率为0.49%，即每204例妊娠中即有1例发生肾结石。其二，妊娠期肾结石与子痫前期（preeclampsia）、尿路感染（urinary tract infection）的发生显著相关，同时会增加低出生体重儿、早产及剖宫产分娩的发生风险；但妊娠期肾结石与胎膜早破（premature rupture of membranes）或新生儿死亡率无显著关联。其三，无论采用药物治疗还是手术治疗，报告的产科并发症均较为有限，但多数研究未提供对比性结局数据，因此无法开展正式的荟萃分析。尽管妊娠期肾结石相对罕见，但可能会增加严重不良产科结局的发生风险。不过仍需开展进一步研究，以明确这些产科结局是由肾结石直接导致，还是由其他混杂因素所介导。因此，建议肾结石孕妇接受多学科协作诊疗，并接受针对妊娠的个性化咨询。