The Research On Genetic Test And Pregnancy Outcome Of Fetuses With Congenital Anomalies Of The Kidney And Urinary Tract

Objective:To explore the genetic basis and pregnancy outcomes of fetal urinary system anomalies.Methods:A retrospective study was conducted on 1197 cases of congenital urinary abnormalities in our hospital from January 2014 to June 2020,and their ultrasound categories were classified.413 patients agreed to do prenatal dignosis by chromosomal karyotype analysis,chromosomal microarray analysis(CMA),and/or whole exome sequencing(WES).Pregnancy outcomes were analyzed in all cases.Result:The main ultrasonographic features of CAKUT were hydronephrosis,multicystic dysplastic kidney,renal agenesis,and duplex kidney.Of 413 fetuses that underwent prenatal genetic tests,80 cases(19.37%,80/413)had clinically significant abnormal results,including 25 fetuses with abnormal chromosome number,2 fetuses with abnormal chromosome structural,and 40 fetuses with pathogenic copy number variations/variants of unknown significance.Chromosome 22q11.2 deletion syndrome is probably the most common pathogenic copy number variation in CAKUT.Of the26 fetuses that underwent whole exome sequencing(WES),13(50.00%,13/26)had pathogenic/likely pathogenic/variation uncertain significance results.The incidence of genetic abnormalities was significantly lower for isolated CAKUT(11.36%,36/317)than for CAKUT with additional anomalies(45.83%,44/96;p < 0.05).Among all follow-up cases,there were 755 live births,331 cases of termination of pregnancy,10 cases of in utero deaths,and 3 miscarriages;The remaining 98 cases had unknown or missed pregnancy outcomes.490 patients were also diagnosed with urinary abnormalities on postpartum ultrasonography,in which 56 underwent surgery,which was most commonly caused by ureteropelvic junction obstruction,and all recovered well,except for 1 patient with hydronephrosis,who showed no significant improvement after surgery.Thirteen fetuses died shortly after birth,of which,only 3deaths were due to urinary obstruction and 2 cases were due to infantile polycystic kidney disease.The growth and development of the remaining 423 cases were normal after birth.The rate of operation after birth was 15.94%(40/251)with hydronephrosis,and the postoperative recovery was good.3 cases of 109 cases live births with multicystic dysplastic kidney underwent postnatal nephrectomy(2.75%,3/109).Among children with genetic abnormalities of the urinary system,growth retardation occurred in 4 of 13 live births,and one died of heart disease one year postpartum.Of the 329 children with normal prenatal genetic results,243 were live births,of which 2died shortly after birth,70 were artificially terminated,4 died in utero,and 12 were lost to follow-up.The anteroposterior diameter of renal pelvic(APD)in the third trimesters was used to predict the necessity of postnatal surgery.When the APD cutoff was 17.5 mm,the predicted sensitivity and specificity were 63.2% and 94.7%,respectively.Conclusion:The main genetic causes of isolated CAKUT were copy number variations(CNVs)and genetic abnormalities.CMA has important value in CAKUT fetuses with normal karyotype and can increase the detection rate by 4%;WES can significantly improve the genetic detection rate of CAKUT fetuses with unknown causes in prenatal diagnosis.Fetuses with isolated urinary abnormalities have a good prognosis after birth.Fetuses with hydronephrosis are more likely to undergo surgery after birth than those with other urinary abnormalities,but most have a good prognosis.Fetuses with combined abnormalities of other systems,especially cardiovascular and nervous systems,have a poor prognosis.The probability of poor prognosis in isolated fetal CAKUT without genetic abnormality was 2.56%.A third-trimester APD ≥ 17.5 mm predicted the necessity of postnatal surgery.