Transvaginal sonographic detection of skeletal anomalies in the first and early second trimesters

We report the detection of 42 cases of musculoskeletal anomalies routinely screened by transvaginal sonography at 12-16 weeks of gestation out of 7325 examined pregnant women (incidence of 0·57 per cent).     

Blood chemistry of human fetuses in the second and third trimesters

Six biochemical parameters and four enzyme activities were determined from the serum of 76 healthy and 56 pathological human fetuses between the 20th and 38th week of pregnancy. In the normal fetuses studied within that period, creatinine, immunoglobulin M, lactate dehydrogenase, and gamma-glutamyltransferase increased; haemoglobin F and glucose progressively decreased; and alkaline phosphatase was at a peak around the 26th week; cholesterol and triglycerides were always low. The same parameters were also measured in some of the pathological fetuses and compared with their normal counterparts.     

Prenatal diagnosis of purine nucleoside phosphorylase deficiency in the first and second trimesters of pregnancy

Prenatal diagnosis was performed in two successive pregnancies of a mother with a previous child with purine nucleoside phosphorylase (PNP) deficiency. In one pregnancy, an affected fetus was diagnosed in the 18th week of gestation after the demonstration of PNP deficiency in cultured amniotic fluid cells. Also an abnormal purine nucleoside profile was found in the amniotic fluid. The diagnosis of an affected fetus was confirmed by the analysis of cultured fetal skin fibroblasts and placental villi. The complete deficiency of PNP activity in placental villi confirms that the prenatal diagnosis of this disorder is possible by the direct investigation of chorionic villi. In the subsequent pregnancy, a heterozygous fetus was predicted in the tenth week of pregnancy by using chorionic villi.     

Prenatal diagnosis of isovaleric acidaemia by enzyme and metabolite assay in the first and second trimesters

Isovaleric acidaemia (IVA) is caused by a deficiency of isovaleryl CoA dehydrogenase. The diagnosis can be established biochemically by the demonstration of increased levels of isovalerylglycine (IVG) and 3-hydroxyisovaleric acid in urine and by the deficiency of incorporation of radiolabel from [¹⁴C]isovaleric acid in macromolecules in cultured fibroblasts. This paper reports a consecutive series of 24 prenatal diagnoses in pregnancies at high risk, using both methods-metabolite and indirect enzyme assay. Affected fetuses were diagnosed in four pregnancies: three in the second trimester and one recent case in the first trimester. The latter represents the first reported case of a first-trimester diagnosis of IVA by direct analysis of chorionic villi. We also report the first demonstration of strongly accumulated IVG in the amniotic fluid in the 12th week of an affected pregnancy.     

CA-125 as a maternal serum marker for Down's syndrome in the first and second trimesters

CA-125, alpha-fetoprotein (AFP), and human chorionic gonadotropin (HCG) were determined in maternal serum in the first trimester from 14 women with a Down's syndrome fetus and 61 women with a healthy fetus. In the second trimester, 15 and 60 serum samples were determined from women with a Down's syndrome and a healthy fetus respectively. In both trimesters, maternal serum CA-125 was found to be elevated in Down's syndrome pregnancies compared with controls. Using discrimination functions, our preliminary results indicate that CA-125 is a better marker than AFP and HCG respectively for a Down's syndrome fetus in the first trimester and improves the detection rate in the second trimester.     

Rapid whole exome sequencing in pregnancies to identify the underlying genetic cause in fetuses with congenital anomalies detected by ultrasound imaging

Objective

The purpose of this study was to explore the diagnostic yield and clinical utility of trio-based rapid whole exome sequencing (rWES) in pregnancies of fetuses with a wide range of congenital anomalies detected by ultrasound imaging.

Methods

In this observational study, we analyzed the first 54 cases referred to our laboratory for prenatal rWES to support clinical decision making, after the sonographic detection of fetal congenital anomalies. The most common identified congenital anomalies were skeletal dysplasia (n = 20), multiple major fetal congenital anomalies (n = 17) and intracerebral structural anomalies (n = 7).

Results

A conclusive diagnosis was identified in 18 of the 54 cases (33%). Pathogenic variants were detected most often in fetuses with skeletal dysplasia (n = 11) followed by fetuses with multiple major fetal congenital anomalies (n = 4) and intracerebral structural anomalies (n = 3). A survey, completed by the physicians for 37 of 54 cases, indicated that the rWES results impacted clinical decision making in 68% of cases.

Conclusions

These results suggest that rWES improves prenatal diagnosis of fetuses with congenital anomalies, and has an important impact on prenatal and peripartum parental and clinical decision making.     

Transvaginal sonography—detection of findings suggestive of fetal chromosomal anomalies in the first and early second trimesters

Over a 4-year period, 14 dyskaryotic fetuses were diagnosed by amniocentesis, performed after early detection of malformations using transvaginal sonography (TVS). These 14 dyskaryotic fetuses were detected out of 4878 sonographic screenings performed by TVS between 9 and 16 weeks' gestation. Twenty-eight per cent of the referrals were at high risk and 72 per cent were at low risk for fetal malformations. Two hundred and twenty-nine fetuses (4.7 per cent) of the screened population had 265 anomalies, 39 per cent of them being transient. In 7 of the 14 dyskaryotic fetuses (50 per cent), the sonographically detected anomalies were transient, being undetected by follow-up sonographic screenings at later gestational ages (⩾18 weeks). Postponing the first sonographic scan aimed at malformation detection to a later gestational age may lead to transient anomalies and their associated dyskaryosis being missed.     

All-in-one whole exome sequencing strategy with simultaneous copy number variant,single nucleotide variant and absence-of-heterozygosity analysis in fetuses with structural ultrasound anomalies: A 1-year experience

Objective

We performed a 1-year evaluation of a novel strategy of simultaneously analyzing single nucleotide variants (SNVs), copy number variants (CNVs) and copy-number-neutral Absence-of-Heterozygosity from Whole Exome Sequencing (WES) data for prenatal diagnosis of fetuses with ultrasound (US) anomalies and a non-causative QF-PCR result.

Methods

After invasive diagnostics, whole exome parent-offspring trio-sequencing with exome-wide CNV analysis was performed in pregnancies with fetal US anomalies and a non-causative QF-PCR result (WES-CNV). On request, additional SNV-analysis, restricted to (the) requested gene panel(s) only (with the option of whole exome SNV-analysis afterward) was performed simultaneously (WES-CNV/SNV) or as rapid SNV-re-analysis, following a normal CNV analysis.

Results

In total, 415 prenatal samples were included. Following a non-causative QF-PCR result, WES-CNV analysis was initially requested for 74.3% of the chorionic villus (CV) samples and 45% of the amniotic fluid (AF) samples. In case WES-CNV analysis did not reveal a causative aberration, SNV-re-analysis was requested in 41.7% of the CV samples and 17.5% of the AF samples. All initial analyses could be finished within 2 weeks after sampling. For SNV-re-analysis during pregnancy, turn-around-times (TATs) varied between one and 8 days.

Conclusion

We show a highly efficient all-in-one WES-based strategy, with short TATs, and the option of rapid SNV-re-analysis after a normal CNV result.     

浅议《周易·同人》的义战思想

战争在古代是国之大事,孔子曰:国之大事,在祀与戎。可见在古代人们把战争看作与祭祀一样重要的大事,所以二者殊途同重,互相交结,有别有同。既有关于战争的祭祀,又有祭祀时形成的卜辞,积累了丰富的战争智慧。《周易·同人》就是此例:之所以叫同人,是因为战亦有道,多助和同。对同人的理解,对于帮助我们理解孟子所说的义战,追溯古人的战争智慧有着重要意义。     

Anhydramnios and cessation of fetal growth in a pregnant mother with polychemotherapy during the second trimester

This paper discusses the case of a pregnant woman with polychemotherapy during the second trimester of pregnancy for rhabdomyosarcoma of the face and cessation of fetal growth with disappearance of amniotic fluid after the first course of therapy.