Comprehensive analysis of isolated mild or moderate renal pelvis separation in singleton foetuses: Causes, prognosis, and clinical implications

Comprehensive analysis of isolated mild or moderate renal pelvis separation in singleton foetuses: Causes, prognosis, and clinical implications | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL This is a preprint and has not been peer reviewed. Data may be preliminary. 17 December 2025 V1 Latest version Share on Comprehensive analysis of isolated mild or moderate renal pelvis separation in singleton foetuses: Causes, prognosis, and clinical implications Authors : Man Liu 0009-0001-3980-3703 , Shaoping Zheng , Linge Song , Guiyun Zheng , Junbo Li , Wei Cai , Yunshuang Bai , Xiangyu Liu , and Yuanling Xiao [email protected] Authors Info & Affiliations https://doi.org/10.22541/au.176596930.05603347/v1 257 views 135 downloads Contents Abstract Supplementary Material Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract OBJECTIVE: Foetal renal pelvis separation identifiable via prenatal ultrasound and other screening methods.This study estimated probable causes associated with mild or moderate isolated renal pelvis separation and documented the prognosis and outcomes observed.To evaluate the association between mild or moderate isolated renal pelvis separation and chromosomal aberrations. STUDY DESIGN: In total, 701 foetuses with mild or moderate separation were retrospectively analysed. Postnatal follow-up was successfully completed for 685 individuals. The follow-up time ranged from 1 month to 9 years after birth. Collected data included prenatal screening or diagnostic data, pregnancy outcomes, gestational age at delivery, birth weight/length, sex, neonatal assessment, postnatal reevaluation, need for neonatal surgery, and timing details. RESULTS: Male infants accounted for 72.99% of the followed cases (500/685). In all, 111 pregnant women underwent amniocentesis; among these, 13 had abnormal results, yielding a positive rate of 11.71% (13/111). Of these, 5 (4.5%) foetal aneuploidies/unbalanced rearrangements and 1 (0.9%) balanced translocations were identified by means of standard karyotyping. On microarray, 3 samples were identified as having copy-number variants; of these, 2 (1.8%) had P/LP CNVs, and 1 (0.9%) had VUS CNVs. In addition, genetic abnormalities was identified in 4 cases(3.6%).Five (0.72%) newborns required surgical treatment. CONCLUSION: Our study further supporting that it is not justified to perform an invasive test for isolated mild hydronephrosis but aneuploidy screening has been suggested.When mild or moderate isolated ANH is detected, clinicians should consider repeat ultrasound evaluation. If other contributing factors are identified, further genetic evaluation should be performed. Title Page Comprehensive analysis of isolated mild or moderate renal pelvis separation in singleton foetuses: Causes, prognosis, and clinical implications Author: Man Liu #1 ，Shaoping Zheng #2 ，Linge Song #1 ，Guiyun Zheng 1 ，Junbo Li 1 ，Wei Cai 1 ，Yunshuang Bai *3 ，Xiangyu Liu *1 ，Yuanling Xiao *1 1 Obstetrics and gynecology Center, Zhujiang Hospital of Southern Medical University, Guangzhou, China 2 The First Affiliated Hospital,Sun Yat-sen University，Guangzhou, China 3 Sanshui Maternity and Child Healthcare Hospital，Foshan，China # :These authors contributed equally to this work and share first authorship. Man Liu Email: [email protected] Shaoping Zheng Email: [email protected] Linge Song Emial: [email protected] Guiyun Zheng Email: [email protected] Junbo Li Email: [email protected] Wei Cai Email: [email protected] * Corresponding authors: Yuanling Xiao Address: No. 253, middle Industrial Avenue, Guangzhou City, Guangdong Province Email: [email protected] Xiangyu Liu Address: No. 253, middle Industrial Avenue, Guangzhou City, Guangdong Province Email: [email protected] . Yunshuang Bai Address: No. 10, Kangle Road, Xinan Street, Sanshui District, Foshan City, Guangdong Province, China Email: [email protected] Comepeting interests: The authors declare that they have no known competing financial interests or personal relationshipsthat could have appeared to influence the work reported in this paper. Funding: Not applicable. Informed Consent: All participants provided informed consent before taking part in the study. They were informed of the purpose of the research, how their data would be used, and their right to withdraw at any time. Author Contributions Man Liu wrote the paper and conceived and designed the experiments; Shaoping Zheng and Linge Song performed the analysis and interpretation of data.Yunshuang Bai and Guiyun Zheng collected the data and provided the sample for this study. Junbo Li and Wei Cai contributed to drafting the manuscript. All authors have read and approved the final submitted manuscript.Xiangyu Liu revised it critically for important intellectual content. Yuanling Xiao is the guarantor for the article who accepts full responsibility for the conduct of the study, had access to the data, and oversaw the decision to publish. Data availability: Data are available from the corresponding author on reasonable request. Abstract: OBJECTIVE: Foetal renal pelvis separation identifiable via prenatal ultrasound and other screening methods.This study estimated probable causes associated with mild or moderate isolated renal pelvis separation and documented the prognosis and outcomes observed.To evaluate the association between mild or moderate isolated renal pelvis separation and chromosomal aberrations. STUDY DESIGN: In total, 701 foetuses with mild or moderate separation were retrospectively analysed. Postnatal follow-up was successfully completed for 685 individuals. The follow-up time ranged from 1 month to 9 years after birth. Collected data included prenatal screening or diagnostic data, pregnancy outcomes, gestational age at delivery, birth weight/length, sex, neonatal assessment, postnatal reevaluation, need for neonatal surgery, and timing details. RESULTS: Male infants accounted for 72.99% of the followed cases (500/685). In all, 111 pregnant women underwent amniocentesis; among these, 13 had abnormal results, yielding a positive rate of 11.71% (13/111). Of these, 5 (4.5%) foetal aneuploidies/unbalanced rearrangements and 1 (0.9%) balanced translocations were identified by means of standard karyotyping. On microarray, 3 samples were identified as having copy-number variants; of these, 2 (1.8%) had P/LP CNVs, and 1 (0.9%) had VUS CNVs. In addition, genetic abnormalities was identified in 4 cases(3.6%).Five (0.72%) newborns required surgical treatment. CONCLUSION: Our study further supporting that it is not justified to perform an invasive test for isolated mild hydronephrosis but aneuploidy screening has been suggested.When mild or moderate isolated ANH is detected, clinicians should consider repeat ultrasound evaluation. If other contributing factors are identified, further genetic evaluation should be performed. Keywords: chromosomal microarray analysis; copy number variants;foetal renal pelvis separation; antenatal hydronephrosis ;prognosis;follow up;cause;prenatal diagnosis;exome sequencing Main body of text INTRODUCTION Foetal renal pelvis separation, or antenatal hydronephrosis (ANH), is characterised by dilation of the renal pelvis and represents the most common urinary tract abnormality in foetuses. The diagnostic criteria are as follows [1]: for gestational weeks 16–27, an anteroposterior diameter (APD) ≥ 4 mm and 10 mm is severe. For gestational weeks 28 and beyond, an APD < 7 mm indicates no renal pelvic separation, ≥ 7 mm and 15 mm indicates severe separation or significant hydronephrosis. According to the Foetal Urology Society [2], the condition occurs in approximately 0.5–1.0% of pregnancies. Most cases are physiological, presenting as transient changes that gradually resolve with gestational development or after birth. A small proportion arises from pathological causes, including structural abnormalities of the urinary tract, chromosomal anomalies, genomic copy number variations (CNVs), and gene variants. The condition is more common in male foetuses and more frequently affects the left kidney [3]. The cause, severity, and co-occurrence of other abnormalities are closely correlated with foetal prognosis. Close monitoring and early identification of pathological cases enable timely intervention, improving outcomes for affected infants. Therefore, it is essential to identify pathological renal pelvis separation to guide prognosis and management. METHODS This retrospective analysis included 701 cases with an initial diagnosis of mild or moderate isolated ANH by ultrasound at Zhujiang Hospital of Southern Medical University, spanning January 2014 to August 2023. All of these subjects fulfilled the inclusion criteria: singleton pregnancy; isolated ANH; no systemic or syndromic disorders; no multiple foetal anomalies; and complete follow-up. Diagnostic criteria for ANH were as per the standards described above. For cases with abnormal renal findings, we retrieved and reviewed the clinical details, including genetic testing results (Down syndrome screening, noninvasive prenatal testing [NIPT], chromosome analysis, chromosomal microarray analysis [CMA], or exome sequencing [WES]) and pregnancy outcomes. Regular ultrasound follow-ups were recommended for these pregnant women every 2 weeks after the initial test, with subsequent follow-ups scheduled every 4 weeks if the condition remained stable. The women had been counselled and had consented to their data being used retrospectively for clinical research. Postnatal assessments were performed at birth or later through telephone interviews using the hospital’s clinical follow-up system. The follow-up time ranged from 1 month to 9 years after birth. Collected data included prenatal screening or diagnostic data, pregnancy outcomes (termination of pregnancy, miscarriage, preterm birth, stillbirth), gestational age at delivery, birth weight/length, sex, neonatal assessment (survival or live birth requiring medical care), postnatal reevaluation, need for neonatal surgery, and timing details. This study received approval from the Internal Ethics Committee of Zhujiang Hospital, Southern Medical University, Guangzhou, China (No. 2022-KY-043–02). Statistical analysis Continuous variables are reported as the mean (standard deviation), and categorical variables are expressed as the count (percentage). Statistical analyses were performed using SPSS software version 25.0 (IBM Corp., Armonk, NY, USA). The χ² test was used to compare the distribution of ANH to investigate and summarise potential aetiologies of mild ANH, evaluate its prognosis, determine the need for surgical intervention, assess the association with chromosomal abnormalities, and support clinical diagnosis and treatment. Logistic regression analysis was also conducted to identify possible risk factors for isolated ANH. A p-value < 0.05 was considered statistically significant. Participant characteristics Ultimately, 685 cases with an initial diagnosis of isolated mild or moderate ANH were included. Maternal age was 19–46 (30.20 ± 4.34) years. Overall, 72.99% (500/685) of infants were boys (Table 1).The first ultrasound diagnosis indicated mild or moderate ANH in all cases, with the gestational age at the time of initial ultrasound diagnosis ranging from 16+3 to 39+6 weeks. Results of Down syndrome screening In total, 561 pregnant women underwent Down syndrome screening during the early and/or mid-pregnancy periods. In all, 449 cases were classified as low risk for foetal chromosomal abnormalities, 43 as high risk, 53 as borderline risk, and 16 presented with abnormal single indicators. The specific features are summarised in Table 2. NIPT and prenatal diagnostic results Pregnant women were recommended to undergo NIPT if mild or moderate ANH was detected during prenatal ultrasound screening, and to proceed with prenatal diagnostic testing if ANH was diagnosed or if NIPT results were negative. Of the 254 pregnant women who underwent NIPT, 238 tested positive and 16 tested negative, yielding a positive rate of 93.70% (238/254). The 16 negative cases subsequently underwent amniocentesis, and the NIPT results matched puncture findings in 3 cases. The positive predictive value of NIPT was 18.8% (3/16). The specific features are summarised in Table 3. In total, 111 pregnant women underwent amniocentesis due to advanced maternal age, with high-risk status indicated via Down syndrome screening or NIPT. None of the foetuses presented with other structural malformations; 13 had abnormal results, for a positive rate of 11.71% (13/111). Of these, 5 (4.5%) foetal aneuploidies/unbalanced rearrangements and 1 (0.9%) balanced translocations were identified by means of standard karyotyping. On microarray, 3 samples were identified as having copy-number variants; of these, 2 (1.8%) had P/LP CNVs, and 1 (0.9%) had VUS CNVs. In addition, genetic abnormalities was identified in 4 cases(3.6%). The specific characteristics of these cases are summarised in Table 4. Outcomes of infants and newborns Six foetuses were delivered early due to chromosomal or genetic abnormalities, or to insufficient amniotic fluid. The specific characteristics of these cases are summarised in Table 5.One of these cases resulted in stillbirth at 36 weeks. Another baby, born prematurely, passed away 1 month after birth. Five of the infants underwent surgical treatment between 10 days and 3 months of age. During pregnancy or after birth, 494 cases showed full recovery. Meanwhile, to date, 186 cases have not fully recovered but have remained stable without the need for surgery. DISCUSSION Woodward et al. [4] studied newborns and foetal hydronephrosis, and found that 48% of cases involved transient hydronephrosis, 15% were physiological, 11% resulted from an obstruction at the renal pelvis–ureter junction, 9% involved vesicoureteral reflux, 4% were identified as megaureter, 2% were due to duplicated kidneys, 1% had posterior urethral valves, and the remaining cases had unknown causes. Overall, 63% of the cases were likely to resolve spontaneously. Most of the literature supports the view that mild fetal pyelectasis constitutes one of the most frequent reports found in ultrasound screening in the second and third trimester of pregnancy and the majority of cases recover or improve within 1 year of birth [5]. However, some cases of pyelectasis, which were discovered during prenatal life, soon revealed pathologies that needed medical or surgical treatment. In our study, five infants (0.73% of the sample, including one girl and four boys) underwent pyeloureteroplasty after birth. The prenatal diagnosis of mild pyelectasis remains essential for early detection of pathological hydronephrosis caused by obstruction or reflux. Foetal ANH is more common in male foetuses, possibly attributable to anatomical factors. Males have greater intrauterine urinary pressure than females, which may result in distortion and deformation at the ureter-bladder junction, causing dilation of the ureter and renal pelvis [6]. Indeed, in our study, 72.99% of mild or moderate cases involved male infants, supporting a possible anatomical predisposition. ANH may be associated with chromosomal or genetic abnormalities [7]. In this study, 254 pregnant women underwent noninvasive prenatal genetic testing. Of these, 238 tested positive and 16 tested negative, for a positive rate of 93.70% (238/254). The 16 negative cases proceeded to amniocentesis, and in 3 cases the results matched those of NIPT. Thus, the positive predictive value of NIPT was 18.8% (3/16).Although the positive predictive value of NIPT is not particularly high, we still recommend it for pregnant women presenting with isolated mild or moderate foetal ANH, especially when additional soft ultrasound markers are detected, such as the absence of the nasal bone or the presence of a bright spot in the left ventricle. Renal pyelectasis, defined as an anteroposterior measurement > 4 mm, is observed in approximately 20–25% of foetuses diagnosed with trisomy 21 [8]. It has been reported that P or LP CNVs were detected in approximately 1.7% of the patients with normal ultrasound examination results and normal karyotyping.Similarly, the incidence of P or LP CNVs was 1.3% (96 of 7255) in gravidas with normal fetal ultrasounds who underwent amniocentesis owing to AMA or high-risk maternal serum[10]. Previous reports suggest a lower incidence, citing pathogenic or likely pathogenic CNVs in just 2.37% of isolated, mild ANH cases [9]. In our cohort, 13 (11.71%,13/111) cases showed chromosomal or genetic abnormalities and a similarly low P/LP CNV rate (1.8%, 2/111) for isolated fetal pyelectasis. Our study further supporting that it is not justified to perform an invasive test for this finding and aneuploidy screening has been suggested. Three cases showed disease progression in follow-up ultrasound examinations: one case developed into severe ANH, further investigation revealed a variant in the KAT6B gene, which encodes histone acetyltransferase. This variant is associated with Genitopatellar syndrome—a rare genetic disorder characterized by microcephaly, severe psychomotor retardation, coarse facial features, congenital flexion contractures of the lower limbs, patellar anomalies or absence, and genitourinary abnormalities [11]. Remarkably, the infant in our study survived and was healthy, despite the diagnosis.In two other cases, genetic abnormalities coincided with additional prenatal findings including excessive amniotic fluid and shortened long bones. These observations suggest that when mild or moderate isolated ANH is detected, clinicians should consider repeat ultrasound evaluation. When other contributing factors are identified including advanced maternal age, abnormal skeletal measurements, excess amniotic fluid, or multiple soft markers further genetic evaluation should be performed. CONCLUSION The main strength of this study lies in its large cohort drawn from a single centre, offering rare insight into the aetiology and prognosis of isolated foetal ANH. However, as a retrospective study, postnatal confirmation of all abnormal cases was limited, introducing a degree of uncertainty in prognostic conclusions. Based on pregnancy outcomes and follow-up data, isolated foetal ANH with negative results in invasive prenatal testing generally has a favourable prognosis. These findings suggest that mild renal conditions are best monitored and diagnosed postnatally to avoid risks associated with invasive procedures in late pregnancy. Regular ultrasound follow-up is strongly advised for these patients, initially 2 weeks after the first test and subsequently every 4 weeks if the condition remains stable. While undergoing NIPT is recommended when mild ANH is detected via prenatal ultrasound, it is not mandatory.Amniocentesis may be necessary for the diagnosis of mild ANH, when accompanied by other high-risk factors such as advanced maternal age, excessive amniotic fluid, or shortened long bones. Acknowledgements: We thank participants the help of the TextCheck for editing the English text of a draft of the manuscript. References [1] Nguyen HT, Herndon CD, Cooper C, Gatti J, Kirsch A, Kokorowski P, Lee R, Perez-Brayfield M, Metcalfe P, Yerkes E, Cendron M, Campbell JB. The Society for Fetal Urology consensus statement on the evaluation and management of antenatal hydronephrosis. J Pediatr Urol. 2010 Jun;6 (3):212–31. doi: 10.1016/j.jpurol.2010.02.205. Epub 2010 Apr 15. [2] M. Arora, A. Prasad, R. Kulshreshtha, A. 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Prenatal chromosomal microarray analysis in 2466 fetuses with ultrasonographic soft markers: a prospective cohort study. Am J Obstet Gynecol 2021; 224: 516. e1–16. [11 ]Kim BR, Han JH, Shin JE, Park MS, Park KI, Namgung R, Lee HJ, Lee JS, Eun HS. Genitopatellar syndrome secondary to de novokat6b mutation: The first genetically confirmed case in South Korea. Yonsei Med J. 2019 Apr;60 (4):395–398. doi: 10.3349/ymj.2019.60.4.395. The English in this document has been checked by at least two professional editors, both native speakers of English. For a certificate, please see: http://www.textcheck.com/certificate/MJGWEC Supplementary Material File (table.docx) Download 20.96 KB Information & Authors Information Version history V1 Version 1 17 December 2025 Copyright This work is licensed under a Non Exclusive No Reuse License. Keywords developing countries: obstetrics and gynaecology doppler ultrasound fetal medicine fetal medicine: perinatal diagnosis—invasive fetal medicine: perinatal diagnosis—ultrasound genetics radiological imaging: ultrasound Authors Affiliations Man Liu 0009-0001-3980-3703 Zhujiang Hospital of Southern Medical University Department of Obstetrics and Gynecology View all articles by this author Shaoping Zheng The First Affiliated Hospital of Sun Yat-sen University View all articles by this author Linge Song Zhujiang Hospital of Southern Medical University Department of Obstetrics and Gynecology View all articles by this author Guiyun Zheng Zhujiang Hospital of Southern Medical University Department of Obstetrics and Gynecology View all articles by this author Junbo Li Zhujiang Hospital of Southern Medical University Department of Obstetrics and Gynecology View all articles by this author Wei Cai Zhujiang Hospital of Southern Medical University Department of Obstetrics and Gynecology View all articles by this author Yunshuang Bai no affiliation View all articles by this author Xiangyu Liu Zhujiang Hospital of Southern Medical University Department of Obstetrics and Gynecology View all articles by this author Yuanling Xiao [email protected] Zhujiang Hospital of Southern Medical University Department of Obstetrics and Gynecology View all articles by this author Metrics & Citations Metrics Article Usage 257 views 135 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Man Liu, Shaoping Zheng, Linge Song, et al. Comprehensive analysis of isolated mild or moderate renal pelvis separation in singleton foetuses: Causes, prognosis, and clinical implications. Authorea . 17 December 2025. DOI: https://doi.org/10.22541/au.176596930.05603347/v1 If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download. For more information or tips please see 'Downloading to a citation manager' in the Help menu . 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