Case report: An asymptomatic mother with an inborn error of cobalamin metabolism (cblC) detected through high homocysteine levels during prenatal diagnosis.

Background: The most common disorder of the intracellular cobalamin metabolism pathway is the combined methylmalonic acidemia and homocysteinemia, cblC type (cblC). There is a variation in its clinical spectrum ranging from severe neonatal-onset forms that are highly fatal to later-onset forms which are milder. In this study, the first case of an asymptomatic Chinese woman with a defect in congenital cobalamin (cblC type) metabolism at prenatal diagnosis due to elevated homocysteine level is identified. Case presentation: The proband, a male child born to a 29-year-old G1P0 mother, admitted to local hospital with feeding disorder, intellectual disability, seizures, microcephaly, as well as heterophthalmos. The level of the urine methylmalonic was elevated. Equally found were increased blood propionylcarnitine (C3) and propionylcarnitine/free carnitine ratio (C3/C0) and decreased methionine levels. The plasma total homocysteine level was elevated at 101.04 µmol/L (normal < 15 µmol/L). The clinical diagnosis of combined methylmalonic acidemia and homocysteinemia was supported. Four years later, the mother of the boy married again and came to us for prenatal diagnosis exactly 15 weeks after her last menstrual period. Subsequently, there is an increase in the amniotic fluid methylmalonate. The level of the amniotic fluid total homocysteine was marginally high. A considerably elevated amniotic fluid C3 was equally observed. In addition, there is a respective significant increase in the plasma and urine total homocysteine at 31.96 and 39.35 µmol/L. After the sequencing of MMACHC genes, it is found that the boy, a proband carried a homozygous mutation of the MMACHC at c.658_660delAAG. While the boy's mother, she carries two mutations in MMACHC: c.658_660delAAG and c.617G>A. The fetus is a carrier of the MMACHC gene. Following the administration of routine treatment, the mother remained symptom-free in the course of pregnancy, and she gave birth to a healthy boy. Conclusion: Variable and nonspecific symptoms characterized the cblC type of methylmalonic acidemia combined with homocysteinemia. Both biochemical assays and mutation analysis are recommended as crucial complementary techniques.

Transvaginal ultrasound parameters to evaluate cervical favorability and predict the outcome of induction of labor.

OBJECTIVE: To compare the values of transvaginal ultrasound (TVU) and Bishop score (BS) for predicting outcomes of induction of labor (IOL). METHODS: The BS and TVU were assessed before IOL. TVU parameters included cervical length (CL) and E-Cervix comprising the cervical hard ratio (HR) and the mean strain level of internal os (IOS). Study end-points included the duration of the latent phase within 15 or 18 h and delivery within 24 h. RESULTS: In multivariable logistic regression models, at the first two end-points, the areas under the curve (AUCs) for CL with HR were 0.733 and 0.777, and the AUCs for CL with IOS were 0.754 and 0.787, respectively, The AUC for HR was 0.750 at the third end-point. With receiver operating characteristic (ROC) analysis, the best cut-off value for CL was ≤1.38 cm and that for IOS was ≥0.35. The AUCs of the TVU scoring system by the cut-off values for CL and IOS for the three end-points were 0.784, 0.833, and 0.855, respectively. The predicting values of both methods were better than those of the BS (AUC = 0.672, 0.694, and 0.687, respectively). CONCLUSION: Cervical length along with E-Cervix showed better predictive values for successful induction compared with the BS.

Correlation between mild fetal ventriculomegaly, chromosomal abnormalities, and copy number variations.

BACKGROUND: Lateral ventriculomegaly is the most common abnormality of the fetal nervous system. This study investigated the incidence of chromosomal abnormalities and copy number variations (CNVs) in fetuses with mild ventriculomegaly (MV) based on various ultrasonic manifestations, identifying their corresponding features via ultrasound examination. METHODS: A retrospective analysis was performed on ultrasound and neurosonogram (NSG) manifestations and genetic profiles of 334 cases with MV and invasive prenatal diagnosis. RESULTS: Three hundred thirty-four cases with fetal MV were assessed via karyotyping. Further chromosomal microarray analysis (CMA) was performed in 182 cases with normal chromosome karyotypes; pathogenic chromosomal copy number variations (CNVs) were found in eight cases with a prevalence of 4.4% (8/182). In this study, the incidence rate of pathogenic abnormalities of chromosomes and CNVs was 5.7% (19/334). Based on whether lateral ventriculomegaly was complicated with other ultrasonic features, the 334 patients were divided into two groups: (1) 175 cases exhibited isolated ventriculomegaly (IVM; 52.4%, 175/334 group A) including two (1.1%, 2/175) with pathogenic chromosomal karyotype abnormalities-both trisomy 21; (2) 159 cases exhibited non-isolated ventriculomegaly (N-IVM; 47.6%, 159/334) with pathogenic chromosomal abnormalities and CNVs detected in17 cases (10.7%, 17/159). The N-IVM group was further divided into two groups: 105 cases exhibited MV with undetermined ultrasonic abnormalities (31.4%, 105/334, group B) with pathogenic chromosomal abnormalities and CNVs detected in eight cases (7.6%, 8/105); 54 cases exhibited MV with structural malformations (16.2%, 54/334, group C) of which nine cases (16.7%, 9/54) presented both pathogenic chromosomal abnormalities and CNVs, and five cases (55.6%, 5/9) were diagnosed with various cortical malformations. The pathogenicity rates of the IVM and N-IVM groups were statistically different (χ2=14.159, p = 0.000). There were significant differences (χ2=7.992, p = 0.005) among groups A, B, and C. CONCLUSIONS: Combinations of various ultrasonic abnormalities significantly affect the risk of pathogenic chromosomal abnormalities and CNVs in fetuses with MV. Cases involving cortical malformations require particular attention to the occurrence of pathogenic genetic abnormalities. When fetal MV is detected, a comprehensive ultrasound examination focusing on undetermined ultrasonic abnormalities is critical. Fetal NSG should be conducted to detect potential cerebral cortical malformation easily missed by routine ultrasound.

Asymmetric cortical development and prognosis in fetuses with isolated mild fetal ventriculomegaly: an observational prospective study.

BACKGROUND: Assessments of cortical development and identifying factors that may result in a poor prognosis for fetuses with isolated mild ventriculomegaly (IMVM) is a hot research topic. We aimed to perform a constant, detailed assessment of cortical development in IMVM fetuses using ultrasound and determine whether asymmetric cortical development occurred. Moreover, we aimed to estimate the prognosis of IMVM fetuses and compare the difference in the prognosis of IMVM fetuses presenting symmetric and asymmetric cortical maturation. METHODS: IMVM was diagnosed by regular ultrasound, neurosonography and fetal MRI. Genetic and TORCH examinations were conducted to exclude common genetic abnormalities and TORCH infection of fetuses. Ultrasound examinations were conducted at an interval of 2-3 weeks to record sulcus development in IMVM fetuses using a scoring system. The neonatal behavioral neurological assessment (NBNA), the Ages and Stages Questionnaire, Third Edition (ASQ-3) and the Bayley Scales of Infant Development, First Edition (BSID-I) were performed after birth. RESULTS: Forty fetuses with IMVM were included: twenty showed asymmetric cortical maturation and twenty showed symmetric cortical maturation. For IMVM fetuses presenting asymmetric cortical maturation, the mean gestational age (GA) at the first diagnosis of relatively delayed development was 24.23 weeks for the parieto-occipital sulcus, 24.71 weeks for the calcarine sulcus, and 26.43 weeks for the cingulate sulcus. All the sulci with delayed development underwent 'catch-up growth' and developed to the same grade as the sulci of the other hemisphere. The mean GA at which the two sides developed to the same grade was 29.40 weeks for the parieto-occipital sulcus, 29.30 weeks for the calcarine sulcus and 31.27 weeks for the cingulate sulcus. The NBNA, ASQ-3 and BSID-I scores of all patients were in the normal range. CONCLUSIONS: IMVM fetuses may show mild asymmetric cortical maturation in the second trimester, but the relatively delayed sulci undergo 'catch-up growth'. The neurodevelopment of IMVM fetuses presenting asymmetric cortical maturation and 'catch-up growth' is not statistically significantly different from IMVM fetuses presenting symmetric cortical maturation.

[Predictive value of cervical length by transvaginal sonography for preterm pregnancy during mid- and late-trimester of pregnancy].

OBJECTIVE: To study the value of cervical length (CL) by transvaginal sonography in the mid-trimester and late-trimester for the prediction of preterm delivery. METHODS: The CL was measured by transvaginal sonography for 5277 pregnant women between 22 - 24 weeks and 28 - 32 weeks gestation, who were prenatal cared and delivered at the First Hospital of Peking University from June 2008 to November 2009. The pregnancy outcomes were followed, and the relationship between CL and preterm delivery and preterm premature rupture of membrane was studied. RESULTS: (1) The incidence of preterm delivery was 5.4% (289/5370) total, among of them the incidence of therapeutic preterm delivery was 1.7% (93/5370), spontaneously preterm delivery was 1.2% (62/5370), and preterm premature rupture of membrane was 2.5% (134/5370). There are 4 cases (4/5370) who occured late abortion. (2) Excluding the 93 women who had therapeutic preterm delivery, the mean CL of 22 - 24 weeks was (38.8 ± 4.0) mm. The relative risk for preterm delivery when the CL < 30 mm was 5.2, when CL < 25 mm, the relative risk was 11.1, and when CL < 15 mm the relative risk for preterm delivery was 13.8. The average CL during 28-32 weeks of gestation was (34.6 ± 4.8) mm, was significantly shorter than that of 22 - 24 weeks (P < 0.05). During this period the relative risk for preterm delivery when the CL < 30 mm was 6.9, when CL < 25 mm, the relative risk was 11.1, and when CL < 15 mm the relative risk for preterm delivery was 20.0. (3) A CL < 30 mm as the cut-off value for predicting preterm delivery during 22 - 24 weeks of gestation has only a 3% sensitivity and 19% positive predictive value, but had a 99% specificity and 96% negative predictive value. The sensitivity, positive predictive value, specificity and negative predictive value for a CL < 30 mm as the cut-off value for predicting preterm delivery during 28 - 32 weeks of gestation was 33%, 21%, 95% and 97% respectively. (4) The total number of preterm premature rupture of membrane pregnant women was 134 (2.5%), who had a mean CL of (38.4 ± 4.7) mm during 22 - 24 weeks of gestation, was similar with the women without preterm premature rupture of membrane (PPROM), but during 28 - 32 weeks of gestation the women who occured PPROM had a mean cervical length of (30.6 ± 8.1) mm, and was significantly shorter than that of women without PPROM (34.7 ± 4.6) mm. CONCLUSIONS: (1) CL in 28 - 32 weeks of gestation is significantly shorter than that of in the mid-gestation, but more than 90% of women has a CL ≥ 30 mm. (2) The shorter the CL is, the greater the relative risk of preterm delivery. According to different CL for clinical consulting objective relative risk could be provide. (3) The CL during 28 - 32 weeks of gestation can also predict preterm delivery, the sensitivity is obviously better than that of 22 - 24 weeks of gestation. (4) The CL during 28 - 32 weeks of gestation is valuable for predicting of PPROM.

[Expression and function of cyclooxygenase-2 in endometrial carcinoma].

OBJECTIVE: To evaluate the cyclooxygenase-2(COX-2) expression at mRNA and protein levels, as well as its clinical significance, and to study the correlation of COX-2 with angiogenesis, apoptosis and estrogen or progestron receptors. METHODS: Forty-one samples of normal endometrium tissues and 52 ones of endometrial carcinomas(EC) were collected, together with their corresponding clinical information. RT-PCR was adopted to determine the expression of COX-2 mRNA. Immunohistochemical staining was engaged to evaluate the protein expression of COX-2, VEGF, Bcl-2 and the MVD marked by CD105. And TUNEL was used to count the apoptosis cells. RESULTS: (1)Significantly higher mRNA and protein levels of COX-2 were found in endometrial carcinomas than in normal endometrial tissues (P<0.001). (2)At protein level, COX-2 expression was related to the grade (P=0.020), but had nothing to do with the stage, pathological type, depth of myometrium invasion and lymph node metastasis.Neither did the level of COX-2 mRNA with all the factors above. (3)The level of COX-2 mRAN had nothing to do with that of protein(P=0.125, r=0.222). (4)The higher the expression of COX -2 protein was, the higher that of VEG, MVD or Bcl-2 was, and the lower the count of apoptosis cells was P<0.05. (5)The upregulation of COX-2 protein had no correlation with ER-alpha and ER-beta. But it had positive correlation with PRA and PRB, P was 0.031 and 0.007, respectively. CONCLUSION: (1)The expression of COX-2 is significantly higher in EC than in normal endometrium tissue, not only at the mRNA level, but also at protein level. (2)At protein level, COX-2 expression is related to the grade, but has nothing to do with the stage, pathological type, depth of myometrium invasion and lymph node metastasis. Neither does the level of COX-2 mRNA with all the factors above. (3)The upregulation of COX-2 protein in EC correlates with the increase of VEGF protein and MVD. (4)The upregulation of COX-2 protein in EC correlates with the increase of Bcl-2 protein and the decrease of apoptosis cells. (5)The upregulation of COX-2 protein in EC has no significant correlation with ER expression, but has something to do with the increase of PRA and PRB.