Etiological Study Of Oligohydramnios Of The Second Trimester Of Pregnancy

Background:oligohydramnios in the second trimester often leads to adverse outcomes,which is highly valued by clinicians.Oligohydramnios in the second trimester can be caused by many factors,the most common is urinary system malformation.At the same time,oligohydramnios can also lead to multiple fetal development problems,such as fetal lung dysplasia,fetal limb compression,and so on.With the development of ultrasonic diagnosis technology,the diagnosis of oligohydramnios in the middle of pregnancy is no longer a difficult problem,but the diagnosis rate of fetal malformation is decreased when the amniotic fluid is too small.To find the exact cause,the proper prenatal consultation for these families and the guidance of the second pregnancy are the problems facing the clinic at present.Therefore,it is important to explore the cause of oligohydramnios in the second trimester.Part one:pathological analysis of 18 autopsy cases of oligohydramnios induced by second trimester of pregnancyObjective:To investigate the autopsy of fetuses induced by oligohydramnios during the second trimester.Methods:from September 2015 to December 2017,18 cases of mid pregnancy complicated with oligohydramnios were collected.Diagnostic criteria:mid trimester of pregnancy(14-27+6 weeks),ultrasound indicates that the vertical depth of the largest amniotic fluid dark area(Maximum vertical pocket,MVP)less than 2cm is oligohydramnios,and less than 1cm is severe amniotic fluid.The criteria were included:(1)the actual gestational weeks after the check of pregnancy were 14w-27+6w in pregnancy;(2)ultrasound showed that amniotic fluid was MVP<<2cm>;(3)fetal death in utero between pregnancy 14w-27+6w,ultrasound indicated oligohydramnios.Exclusion criteria:(1)14W or 28w of pregnant weeks after pregnancy;exposure to toxic substances in pregnancy or angiotensin converting enzyme inhibitors(Angiotensin-converting enzyme inhibitors,ACEI)or angiotensin ? receptor blockers(Angiotensin ? receptor blocker,ARB)antihypertensive drugs and prostaglandin synthetase inhibitors History of medication;third,history of infection during pregnancy;multiple pregnancy.All cases were collected in strict accordance with the above inclusion and exclusion criteria.All cases were confirmed by ultrasonic repeated examination more than 2 times in 2 hospitals or our hospital for 1-2 weeks,and induced abortion in our hospital.All the induced fetus were analyzed by autopsy.Results:18 cases of oligohydramnios were diagnosed by ultrasound.9 cases only showed oligohydramnios,9 cases with oligohydramnios and other abnormal manifestations of ultrasound,3 of them were obviously less than the actual gestational weeks(1 cases of suspicious infantile polycystic kidney)and 7 cases of renal abnormality(5 cases were suggestive of fetal double renal echo enhancement,among which 3 suspicious infants were suspected." Children with polycystic kidney disease;1 cases of double kidneys showed unclear;1 cases of right kidney deficiency,and left renal dysplasia.There were 10 cases of renal abnormality in the autopsy:(1)3 cases of double kidney deficiency,of which 2 cases were enhanced by ultrasound in double renal region;4 cases were polycystic change of kidney(1 cases were not suggestive of renal abnormalities);and 2 cases of double renal cortical dysplasia(these 2 cases were not suggestive of renal abnormalities);(4)1 cases of renal medullary region(this case)Renal abnormalities were not indicated by ultrasound).Conclusion:when 1.oligohydramnios is absent,the diagnostic rate of ultrasound for fetal malformation is decreased.2.there may be abnormal renal microstructures in oligohydramnios.It is necessary for autopsy and further pathological diagnosis of fetuses after induction of labor to help clarify the cause.The second part:the genetic etiology of fetuses with oligohydramnios during the second trimester.Objective:to analyze the cause of the disease from the perspective of genetics by using gene chip technology and whole exon detection technology.Methods:chromosome microarray analysis(Cytogenomic microarray,CMA)and(or)total exon sequencing(WES)were performed on the first part of the collected cases(Whole exome sequencing,WES),and pedigree verification was carried out for the suspected mutation loci of the found.Results:a total of 15 fetuses were detected by CMA,and no abnormalities were found.(2)a total of 12 fetuses were detected by WES.There were 9 cases of no suspected pathogenic genes and 3 cases of suspected pathogenic genes:1 cases of PKD1 gene c.5037C>A(exonl5)and c.10678G>A(exon36)mutation.The disease involved adult polycystic kidney disease(Autosomal dominant polycystic kidney).4P)and c.3070-3071delCT(p.L1024Lfs*17)complex heterozygous mutation,involving the disease of renal tubular dysplasia(Renal tubular dysgenesis,RTD);1 cases of ANKS6 c.2394+1G>A(IVS13),c.621(Exon2)complex heterozygous mutation,involving the disease of the kidney wasting disease type 16.(3)the PHD1 gene mutation family confirmed that the mutation was derived from the parents.The mutation involved the disease as an autosomal dominant hereditary disease.Both parents were not pathogenic and family verification did not pass.The ACE gene and the ANSK6 gene mutation family confirmed that the mutation was from the parents,which were all conformed to the autosomal recessive inheritance.Conclusion:molecular genetic diagnosis is of great importance in the diagnosis of the causes of oligohydramnios in the second trimester and the diagnosis of auxiliary diseases.