A cohort study of fetal urinary tract abnormalities and chromosomal copy number variations: a retrospective analysis of 9-year data

Abstract Objective To investigate the association between ultrasonically detected fetal urinary system abnormalities and chromosomal copy number variations (CNVs) in Heilongjiang Province, northeastern China. Methods Cohort study: 183 fetuses with ultrasound-detected urinary system anomalies (invasive prenatal diagnosis, 2017.01–2025.09, Second Affiliated Hospital of Harbin Medical University) were enrolled. All underwent CNV analysis: 21 without karyotyping, 12 with abnormal karyotypes, 150 with normal karyotypes. The 150 normal-karyotype cases were split into isolated CAKUT (63, 42%) and non-isolated CAKUT (87, 58%) groups; CNV abnormalities were compared between groups. Meta-analysis: Studies on CNVs in CAKUT fetuses (2017.01–2025.09) were retrieved from PubMed, Embase, Web of Science, Cochrane Library, CNKI, Wanfang Data, SinoMed. Pooled effect sizes were calculated via Stata 17.0. Results Among 162 fetuses who underwent conventional karyotyping, chromosomal aneuploidy occurred in 7.41% (12/162). In 150 karyotypically normal cases, pathogenic/likely pathogenic (p/lp) CNVs were detected in 7.33% (11/150): 3.17% (2/63) for isolated CAKUT and 10.34% (9/87) for non-isolated CAKUT (P = 0.120, non-significant). A meta-analysis of 30 studies (9284 pregnant women) demonstrated a weighted pooled incidence of p/lp CNVs of 6% (95% CI 0.05–0.07) in karyotypically normal CAKUT fetuses, with weighted pooled incidences of 5% (95% CI 0.03–0.06) for isolated CAKUT and 8% (95% CI 0.06–0.10) for non-isolated CAKUT. Conclusions This is the first cohort study utilizing nine-year data from Heilongjiang Province, a cold region in northeastern China, to analyze the association between fetal urinary system anomalies and CNVs. In this region, the incidence of p/lp CNVs among CAKUT fetuses with normal karyotypes was 7.33%. Notably, seven pathogenic CNV fragments (deletions at 4p15.31, 5p13.1, 15q11.2, 16p11.2, Xq28, and Xp22.31; duplication at 11q15.5) previously unreported in Northeast China were identified, expanding the genetic spectrum associated with CAKUT in cold regions. The meta-analysis noted that the cumulative crude incidence of p/lp CNV in CAKUT fetuses was 5.71% (498/8,723) across all included studies. Both the cohort study and the meta-analysis showed a numerically higher incidence of p/lp CNVs in non-isolated CAKUT compared with isolated cases (10.34% vs. 3.17%, P = 0.120; 8% vs. 5% weighted pooled incidences from the meta-analysis, respectively), though this difference did not reach statistical significance in the cohort study. Thus, routine CNV screening is recommended for all CAKUT fetuses, particularly non-isolated cases, to comprehensively exclude genetic abnormalities, guiding clinical prenatal diagnosis and genetic counseling.