Chia-Ling Nhan-Chang

Comparative Anatomy of Chromosomal Domains with Imprinted and Non-Imprinted Allele-Specific DNA Methylation

Allele-specific DNA methylation (ASM) is well studied in imprinted domains, but this type of epigenetic asymmetry is actually found more commonly at non-imprinted loci, where the ASM is dictated not by parent-of-origin but instead by the local haplotype. We identified loci with strong ASM in human tissues from methylation-sensitive SNP array data. Two index regions (bisulfite PCR amplicons), one between the C3orf27 and RPN1 genes in chromosome band 3q21 and the other near the VTRNA2-1 vault RNA in band 5q31, proved to be new examples of imprinted DMRs (maternal alleles methylated) while a third, between STEAP3 and C2orf76 in chromosome band 2q14, showed non-imprinted haplotype-dependent ASM. Using long-read bisulfite sequencing (bis-seq) in 8 human tissues we found that in all 3 domains the ASM is restricted to single differentially methylated regions (DMRs), each less than 2kb. The ASM in the C3orf27-RPN1 intergenic region was placenta-specific and associated with allele-specific expression of a long non-coding RNA. Strikingly, the discrete DMRs in all 3 regions overlap with binding sites for the insulator protein CTCF, which we found selectively bound to the unmethylated allele of the STEAP3-C2orf76 DMR. Methylation mapping in two additional genes with non-imprinted haplotype-dependent ASM, ELK3 and CYP2A7, showed that the CYP2A7 DMR also overlaps a CTCF site. Thus, two features of imprinted domains, highly localized DMRs and allele-specific insulator occupancy by CTCF, can also be found in chromosomal domains with non-imprinted ASM. Arguing for biological importance, our analysis of published whole genome bis-seq data from hES cells revealed multiple genome-wide association study (GWAS) peaks near CTCF binding sites with ASM.

The effect of intramuscular progesterone on the rate of cervical shortening

OBJECTIVEnThe purpose of the study was to evaluate whether 17-alpha-hydroxyprogesterone caproate (17-OHPC) exposure is associated with the rate of cervical shortening.nnnSTUDY DESIGNnWomen with a history of spontaneous preterm delivery (PTD) at <37 weeks gestation who had serial cervical length measurements (2009-2012) were identified. 17-OHPC administration and outcome data were collected. We excluded patients with multiple gestations, indicated PTDs, major fetal anomalies, cerclage, and vaginal progesterone use. The rate of cervical shortening was modeled in relation to 17-OHPC status with the use of methods for longitudinal data analysis.nnnRESULTSnTwo hundred thirty-seven patients with 1171 cervical length measurements were included, of whom 184 patients (77.6%) were exposed to 17-OHPC. Gestational age, number of previous PTDs, gestational age at initiation, and interval between cervical length examinations were similar between the 2 groups, although women who were not exposed to 17-OHPC were more likely to have delivered multiples in their previous PTD (24.5% vs 4.4%; P < .01). In the entire cohort, the rate of cervical shortening was identical, regardless of 17-OHPC exposure (0.85 mm per week). Among term deliveries, the rates of cervical shortening per week, on average, were 0.9 and 0.8 mm per week among women with and without 17-OHPC, respectively (P = .76). Among preterm deliveries, the corresponding rates were 0.8 and 1.2 mm, respectively, among women with and without 17-OHPC (P = .67).nnnCONCLUSIONnCervical shortening among women with previous preterm delivery occurs at a similar rate, regardless of exposure to 17-OHPC.

A Parameterized Ultrasound-Based Finite Element Analysis of the Mechanical Environment of Pregnancy

Preterm birth is the leading cause of childhood mortality and can lead to health risks in survivors. The mechanical functions of the uterus, fetal membranes, and cervix have dynamic roles to protect the fetus during gestation. To understand their mechanical function and relation to preterm birth, we built a three-dimensional parameterized finite element model of pregnancy. This model is generated by an automated procedure that is informed by maternal ultrasound measurements. A baseline model at 25 weeks of gestation was characterized, and to visualize the impact of cervical structural parameters on tissue stretch, we evaluated the model sensitivity to (1) anterior uterocervical angle, (2) cervical length, (3) posterior cervical offset, and (4) cervical stiffness. We found that cervical tissue stretching is minimal when the cervical canal is aligned with the longitudinal uterine axis, and a softer cervix is more sensitive to changes in the geometric variables tested.

Congenital parvovirus B19 infection: persistent viremia and red blood cell aplasia

We describe a case of fetal parvovirus B19 infection resulting in preterm birth and leading to hydrops fetalis requiring multiple in utero transfusions. The infant developed chronic postnatal anemia responsive to intravenous immunoglobulin therapy. Serum viral load decreased after immunoglobulin treatment but remained detectable for over 1 year.

Going out on a limb for a difficult diagnosis: a case report

Sacral tumors with fetiform features are rare and pose a diagnostic challenge to the ultrasonologist. Sacrococcygeal teratomas (SCT) and parasitic twins can have very similar sonographic features but have different implications to an affected pregnancy. While postnatal histopathology is ultimately necessary to distinguish between a SCT and a heteropagus twin, certain characteristics, such as the presence of a vertebral column and the pattern and rate of tumor growth, may be useful to guide counseling and management decisions.