Meta-analysis and cohort study examine chromosomal copy number variations in fetuses with urinary tract abnormalities

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.