Improving Prenatal Diagnosis Precision for Congenital Clubfoot by Using Three-Dimensional Ultrasonography.

Prenatal diagnosis of clubfoot traditionally relied on two-dimensional ultrasonography. To enhance diagnosis and predict postnatal outcomes, we examined the parameters that differentiate pathological clubfoot using three-dimensional ultrasonography. In our retrospective study, we examined the findings of prenatal ultrasound and the postnatal outcomes of pregnancies with suspected congenital clubfoot between 2018 and 2021. Based on the three-dimensional perspective, we measured the angles of varus, equinus, calcaneopedal block, and forefoot adduction and compared the sonographic variables between the postnatal treated and non-treated groups. We evaluated 31 pregnancies (47 feet) with suspected clubfoot using three-dimensional ultrasonography. After delivery, a total of 37 feet (78.7%) underwent treatment involving serial casting only or additional Achilles tenotomy. The treated group showed significantly greater hindfoot varus deviation (60.5° vs. 46.6°, p = 0.026) and calcaneopedal block deviation (65.6° vs. 26.6°, p < 0.05) compared to the non-treated group. The calcaneopedal block had an area under the curve of 0.98 with a diagnostic threshold of 46.2 degrees (sensitivity of 97%, specificity of 90%, positive predictive value of 97%, and negative predictive value of 90%). During prenatal evaluation of clubfoot using three-dimensional ultrasonography, the calcaneopedal block deviation has the potential to predict postnatal treatment.

Prenatal screening for neural tube defects: from maternal serum alpha-fetoprotein to ultrasonography.

The two main screening tests during pregnancy are those for chromosomal abnormalities and neural tube defects (NTDs). In particular, for NTDs, measurement of maternal serum alpha-fetoprotein (MSAFP) levels early in the second trimester (15-18 weeks of gestation) has been considered the gold standard screening test for the past 4 decades. However, with remarkable technological advancements and the widespread use of ultrasound during those periods, mid-trimester ultrasonography has gradually replaced the role of measuring MSAFP levels as a screening method for NTDs. This change was initiated more about 10 years ago in some countries, which have issued national guidelines to use mid-trimester ultrasonography instead of measuring MSAFP levels as a prenatal screening method for NTDs. However, no significant changes have occurred in Korea, where second-trimester ultrasonography is routinely performed with high-quality equipment. We aimed to provide information regarding the importance of changing the screening method for NTDs from MSAFP measurement to ultrasonography, and to detail methods of implementing mid-trimester ultrasonography for screening purposes. We also share our experience of operating a prenatal diagnostic program for NTDs without using MSAFP for more than 15 years.

External cephalic version in the outpatient clinic.

The continuous increase in the rates of cesarean section worldwide is concerning. Breech presentation is one of the major indications for cesarean section in most countries. External cephalic version (ECV) can reduce cesarean rates by approximately two-thirds in term breech pregnancies. After introduction of ultrasonography and cardiotocography before and after the procedure, ECV has become much safer. As a result, over-night fasting, intravenous access, and preoperative laboratory tests are no longer recommended as the patient's risk of requiring emergency cesarean section is very low. We have been running the largest ECV clinic in South Korea since 2008, and ECV trials in the outpatient clinic were started in 2015. We want to share our experiences running the ECV clinic for 15 years managing more than 2000 patients.

Omental Incarceration over Twenty Years Presenting as a Hyperechoic Endometrial Mass in a Postmenopausal Woman.

Uterine perforation related with dilatation and curettage (D&C) is an uncommon event. Combined complications such as hemorrhage, adjacent organ injury, and omental incarceration may require an emergent surgical treatment. These are usually evident immediately or several days after the D&C, and a delayed presentation of uterine perforation are extremely rare. Herein, we report a rare case of omental incarceration presenting as a hyperechoic endometrial mass in a postmenopausal woman, diagnosed twenty-three years after the D&C. According to this case, when we encounter a hyperechoic endometrial lesion penetrating the uterine wall in women with a history of an intrauterine procedure such as D&C, we need to consider the possibility of an incarcerated omentum.

A Huge Hemorrhagic Epidermoid Cyst of the Perineum with Hypoechoic Semisolid Ultrasonographic Feature Mimicking Scar Endometriosis.

Epidermoid cysts are small, solitary, and slow-growing lesions that rarely appear in the perineum and mostly arise because of trauma. This study examined a huge perineal epidermoid cyst that slowly grew over eight years in a premenopausal woman. Ultrasonography showed that the hemorrhage in the cyst was a semisolid hypoechoic mass, which mimicked endometrioma, and was tentatively diagnosed as scar endometriosis in the perineum after vaginal delivery. This case study highlights the importance of wide surgical excision and histopathologic diagnosis, even with typical ultrasonography and surgical findings.

A giant symptomatic placental chorioangioma managed with a histoacryl injection.

Chorioangiomas are generally small and associated with favorable outcomes, but large tumors can cause serious fetal complications, such as polyhydramnios, fetal anemia, intrauterine growth restriction, cardiac failure, fetal hydrops, and intrauterine fetal death. Signs of fetal cardiac failure on ultrasonography are indications for urgent in utero interventions. We report a case of a giant chorioangioma causing fetal cardiac failure at 26+3 weeks' gestation, which was treated by embolization of the feeding vessels. We utilized a mixture of n-butyl cyanoacrylate (nBCA, Histoacryl®) and iodized oil (Lipiodol®) as an embolic agent. Fetal hydrops resolved in 4 weeks, and the cardiac size and function normalized 8 weeks after the embolization. A healthy male baby was born at the 37+5th gestational week by cesarean section.

Efficacy of fetal cardiac axis evaluation in the first trimester as a screening tool for congenital heart defect or aneuploidy.

OBJECTIVE: To prove the efficacy of determining the abnormal fetal cardiac axis for screening congenital heart defects (CHDs) and predicting fetal aneuploidy at 11.0 to 13.6 weeks of pregnancy. METHODS: This retrospective study was performed at a single high-risk pregnancy center. The fetal cardiac axis was evaluated between 11.0 and 13.6 weeks of gestation in 142 fetuses. The cardiac axis in a 4-chamber view was measured as the angle between the line tracing the long axis of the heart and the line bisecting the thorax in the anteroposterior direction. A CHD was confirmed based on the second- to third-trimester fetal status or postnatal imaging. Aneuploidy was diagnosed using chorionic villus sampling, amniocentesis, or genetic testing after birth. Fisher's exact test was performed to assess the association between the fetal cardiac axis and the abnormal fetal status. A 2-way contingence table analysis was performed to confirm the efficacy of the fetal cardiac axis as a screening tool. RESULTS: Among the 142 fetuses, 10 had a CHD while 17 had aneuploidy. The abnormal fetal cardiac axis was significantly associated with CHDs (P=0.013) and aneuploidy (P=0.010). None of the fetuses with CHDs or aneuploidy had an isolated abnormal cardiac axis alone without other sonographic findings. The sensitivity of the fetal cardiac axis was 50.0% for CHDs and 41.2% for aneuploidy. CONCLUSION: The fetal cardiac axis can be an additional helpful tool for prenatal screening of CHDs and aneuploidy in the first trimester.

Generation of human androgenetic induced pluripotent stem cells.

In humans, parthenogenesis and androgenesis occur naturally in mature cystic ovarian teratomas and androgenetic complete hydatidiform moles (CHM), respectively. Our previous study has reported human parthenogenetic induced pluripotent stem cells from ovarian teratoma-derived fibroblasts and screening of imprinted genes using genome-wide DNA methylation analysis. However, due to the lack of the counterparts of uniparental cells, identification of new imprinted differentially methylated regions has been limited. CHM are inherited from only the paternal genome. In this study, we generated human androgenetic induced pluripotent stem cells (AgHiPSCs) from primary androgenetic fibroblasts derived from CHM. To investigate the pluripotency state of AgHiPSCs, we analyzed their cellular and molecular characteristics. We tested the DNA methylation status of imprinted genes using bisulfite sequencing and demonstrated the androgenetic identity of AgHiPSCs. AgHiPSCs might be an attractive alternative source of human androgenetic embryonic stem cells. Furthermore, AgHiPSCs can be used in regenerative medicine, for analysis of genomic imprinting, to study imprinting-related development, and for disease modeling in humans.

Heritability of telomere length across three generations of Korean families.

BACKGROUND: Leukocyte telomere length (LTL), an indicator of aging, is influenced by both genetic and environmental factors; however, its heritability is unknown. We determined heritability and inheritance patterns of telomere length across three generations of families. METHODS: We analyzed 287 individuals from three generations of 41 Korean families, including newborns, parents, and grandparents. LTL (the ratio of telomere repeat copy number to single gene copy number) was measured by quantitative real-time PCR. We estimated heritability using the SOLAR software maximum-likelihood variance component methods and a pedigree dataset. With adjustment for age and length of marriage, Pearson's partial correlation was performed for spousal pairs. RESULTS: Heritability of LTL was high in all participants (h2 = 0.64). There were no significant differences in correlation coefficients of telomere length between paternal and maternal lines. There was a positive LTL correlation in grandfather-grandmother pairs (r = 0.25, p = 0.03) but not in father-mother pairs. After adjusting for age and length of marriage, the relationship between telomere lengths in grandfathers and grandmothers disappeared. There were inverse correlations between spousal rank differences of telomere length and length of marriage. CONCLUSIONS: LTL is highly heritable without a sex-specific inheritance pattern and may be influenced by a shared environment.

Reviving external cephalic version: a review of its efficacy, safety, and technical aspects.

Currently, the rate of cesarean sections being performed in Korea is approximately 40%, with Korea ranking 4th among the Organization for Economic Co-operation and Development countries with respect to cesarean deliveries. Breech presentation at term is an important indication for cesarean section among other factors, including medicolegal concerns and pregnancies in women of advanced maternal age. Term breech presentation is associated with a higher fetal mortality rate than that associated with a cephalic presentation. Therefore, in Korea, most of these women deliver by cesarean section to avoid the complications of vaginal breech delivery. However, cesarean section is itself associated with considerable obstetric morbidity and sometimes, mortality. External cephalic version (ECV) is a useful method to reduce the cesarean section rate in women with breech presentation and therefore to reduce the incidence of breech presentation at delivery. Studies have shown that routine use of ECV reduces the cesarean section rate by approximately two-thirds in term pregnancies with breech presentation. ECV is accepted as a safe, efficacious, and cost-effective method and is recommended by both the American College of Obstetricians and Gynecologists and the Royal College of Obstetricians and Gynecologists in all pregnancies with term breech presentation, if not contraindicated. In Korea, although most clinicians are aware of the option of ECV, their relative lack of experience in performing the procedure and fear of complications render them hesitant to perform ECV. This review is aimed at guiding obstetricians by describing the efficacy, safety concerns, and technical aspects of this procedure.

Interference-Aware Routing for Difficult Wireless Sensor Network Environment with SWIPT.

The main challenges of sensing in harsh industrial and biological environments are the limited energy of sensor nodes and the difficulty of charging sensor nodes. Simultaneous wireless information and power transfer (SWIPT) is a non-invasive option to replenish energy. SWIPT harvests energy and decodes information from the same RF signal, which is influencing the design of a wireless sensor network. In multi-hop multi-flow wireless sensor networks, interference generally exists, and the interference has a different influence on SWIPT. Route, interference and SWIPT are dependent. However, existing works consider SWIPT link resource allocation with a given route or only select path for one flow without interference. Therefore, this paper firstly analyzes the influence of interference on SWIPT, and select the SWIPT routing with interference. We design an interference-based information and energy allocation model to maximize the link capacity with SWIPT. Then, we design an interference-aware route metric, formulate SWIPT routing problem, and design an interference-aware SWIPT routing algorithm. The simulation results show that as the number of flows increases, there is more likely to obtain performance gains from interference and SWIPT.

Alteration of Genomic Imprinting Status of Human Parthenogenetic Induced Pluripotent Stem Cells during Neural Lineage Differentiation.

BACKGROUND AND OBJECTIVES: Genomic imprinting modulates growth and development in mammals and is associated with genetic disorders. Although uniparental embryonic stem cells have been used to study genomic imprinting, there is an ethical issue associated with the destruction of human embryos. In this study, to investigate the genomic imprinting status in human neurodevelopment, we used human uniparental induced pluripotent stem cells (iPSCs) that possessed only maternal alleles and differentiated into neural cell lineages. METHODS: Human somatic iPSCs (hSiPSCs) and human parthenogenetic iPSCs (hPgiPSCs) were differentiated into neural stem cells (NSCs) and named hSi-NSCs and hPgi-NSCs respectively. DNA methylation and gene expression of imprinted genes related neurodevelopment was analyzed during reprogramming and neural lineage differentiation. RESULTS: The DNA methylation and expression of imprinted genes were altered or maintained after differentiation into NSCs. The imprinting status in NSCs were maintained after terminal differentiation into neurons and astrocytes. In contrast, gene expression was differentially presented in a cell type-specific manner. CONCLUSIONS: This study suggests that genomic imprinting should be determined in each neural cell type because the genomic imprinting status can differ in a cell type-specific manner. In addition, the in vitro model established in this study would be useful for verifying the epigenetic alteration of imprinted genes which can be differentially changed during neurodevelopment in human and for screening novel imprinted genes related to neurodevelopment. Moreover, the confirmed genomic imprinting status could be used to find out an abnormal genomic imprinting status of imprinted genes related with neurogenetic disorders according to uniparental genotypes.

Extra-adrenal paraganglioma masquerading as severe preeclampsia.

Paraganglioma in pregnancy is an extremely rare condition and its diagnosis is often delayed because the clinical symptoms can mimic those of preeclampsia or gestational hypertension. Here, we report the case of a 32-year-old, gravida 2, para 1 woman who presented with severe headache, palpitation, and sweating at 37 weeks' gestation. Although emergent cesarean section was performed on the assumption of severe preeclampsia, blood pressure fluctuated and heart rate remained tachycardiac. We suspected that she might have thromboembolic lesion in the chest or pheochromocytoma. Chest and abdominal computed tomography revealed a 4 cm mass in the left para-aortic space. Serum and urinary catecholamine levels were found to be significantly increased. She underwent laparoscopic mass removal and the pathology confirmed paraganglioma. When typical paroxysmal hypertension is accompanied by headache, palpitation, and sweating during pregnancy, adrenal tumors should be considered.

Novel imprinted single CpG sites found by global DNA methylation analysis in human parthenogenetic induced pluripotent stem cells.

Genomic imprinting is the process of epigenetic modification whereby genes are expressed in a parent-of-origin dependent manner; it plays an important role in normal growth and development. Parthenogenetic embryos contain only the maternal genome. Parthenogenetic embryonic stem cells could be useful for studying imprinted genes. In humans, mature cystic ovarian teratomas originate from parthenogenetic activation of oocytes; they are composed of highly differentiated mature tissues containing all three germ layers. To establish human parthenogenetic induced pluripotent stem cell lines (PgHiPSCs), we generated parthenogenetic fibroblasts from ovarian teratoma tissues. We compared global DNA methylation status of PgHiPSCs with that of biparental human induced pluripotent stem cells by using Illumina Infinium HumanMethylation450 BeadChip array. This analysis identified novel single imprinted CpG sites. We further tested DNA methylation patterns of two of these sites using bisulfite sequencing and described novel candidate imprinted CpG sites. These results confirm that PgHiPSCs are a powerful tool for identifying imprinted genes and investigating their roles in human development and diseases.

Higher maternal vitamin D concentrations are associated with longer leukocyte telomeres in newborns.

Gestational vitamin D insufficiency is related with increased risks of various diseases and poor health outcomes later in life. Telomere length at birth or early in life is known to be a predictor of individual health. Both vitamin D and telomere length are related with various health conditions, and vitamin D concentrations are associated with leukocyte telomere lengths in women. We investigated the association between maternal vitamin D concentrations and newborn leukocyte telomere lengths. This cross-sectional study included 106 healthy pregnant women without adverse obstetric outcomes and their offspring. We examined the maternal age, weight before pregnancy, health behaviours, and nutritional intakes, along with each newborn's sex and birthweight, and we measured maternal height, telomere length, total white blood cell count, and glycosylated haemoglobin as covariates. Pearson's correlation coefficients were calculated to evaluate the relationship between the baseline variables and newborn leukocyte telomere lengths. To confirm that there was an independent association between newborn leukocyte telomere lengths and maternal vitamin D concentrations, we performed a stepwise multiple linear regression analysis. Newborn leukocyte telomere lengths correlated positively with maternal leukocyte telomere lengths (r = .76, p < .01), maternal 25-hydroxyvitamin D concentrations (r = .72, p < .01), maternal energy intakes (r = .22, p = .03), and newborn body weights (r = .51, p < .01). In the multivariate model, newborn leukocyte telomere lengths were associated with maternal vitamin D concentrations (ß = .33, p < .01). These findings suggest that the maternal vitamin D concentration during pregnancy may be a significant determinant of the offspring's telomere length.

External cephalic version experiences in Korea.

OBJECTIVE: The aim of this study was to evaluate obstetric outcomes of external cephalic version (ECV) performed at or near term. METHODS: Single pregnant woman with breech presentation at or near term (n=145), who experienced ECV by one obstetrician from November 2009 to July 2014 in our institution were included in the study. Maternal baseline characteristic and fetal ultrasonographic variables were checked before the procedure. After ECV, the delivery outcomes of the women were gathered. Variables affecting the success or failure of ECV were evaluated. RESULTS: Success rate of ECV was 71.0% (n=103). Four variables (parity, amniotic fluid index, fetal spine position and rotational direction) were observed to be in correlation with success or failure of ECV. In contactable 83 individuals experienced successful ECV, cesarean delivery rates were 18.1%, 28.9%, and 5.3% in total, nulliparas, and multiparas, respectively. CONCLUSION: Based on the results, ECV is proposed to be safe for both mother and her fetus. In addition, it is a valuable procedure that increases probability of vaginal delivery for women with breech presentation.

Primary cervical choriocarcinoma during viable intrauterine pregnancy.

A 31-year-old multigravida woman at 27 weeks' gestation was admitted with vaginal bleeding and a hypervascular mass near the cervix on ultrasonography. After discharge with improvement, she was readmitted the next day for uncontrolled, heavy vaginal bleeding and underwent emergency cesarean section at 29 weeks' gestation. A 3-cm friable mass found near the cervix was removed surgically; this lesion was shown to be primary cervical choriocarcinoma. On the 17th postoperative day the patient underwent total abdominal hysterectomy with preservation of both ovaries and biopsy was performed on the right ovary. The International Federation of Gynecology and Obstetrics (FIGO) stage was I and her World Health Organization prognostic score was 9, representing high risk. The patient received three rounds of chemotherapy until achieving three consecutive normal human chorionic gonadotropin levels with two additional courses to address risk of relapse. DNA genotyping on short tandem repeat polymorphism confirmed the gestational choriocarcinoma.

Prune-belly syndrome detected by ultrasound in the first trimester and the usefulness of vesicocentesis as a modality of treatment.

Prune-belly syndrome may be related to lower urinary tract obstruction (LUTO). LUTO in the early gestational age exacerbates fetal renal function and may require intrauterine intervention. If early developed LUTO causes bladder distension and abdominal musculature deficiency, it will result in prune belly syndrome. Therefore, early detection of the disease and proper treatment before the renal impairment is important. However, there are few literatures concerning the treatment of prune belly syndrome in the first trimester. We report a case of prune belly syndrome diagnosed at 11+6 weeks of gestation and the value of vesicocentesis as a modality of treatment. Ultrasound showed dilated fetal bladder and vesicocentesis was successful in reducing the volume of the bladder. However, the pregnancy was terminated upon request.

Congenital chloride diarrhea in dizygotic twins.

Congenital chloride diarrhea (CLD) is a rare inherited autosomal recessive disorder. Mutations of the solute carrier family 26 member 3 gene cause profuse, chloride ion rich diarrhea, which results in hypochloremia, hyponatremia and metabolic alkalosis with dehydration. If a fetal ultrasound shows bowel dilatation suggestive of bowel obstruction, or if a neonate shows persistent diarrhea and metabolic alkalosis, CLD should be considered in the differential diagnosis. The severity of CLD varies, but early detection and early therapy can prevent complications including growth failure. We report a case of dizygotic twins affected by CLD who had been born to non-consanguineous parents. Both of them showed growth failure, but one of the twins experienced worse clinical course. He showed developmental delay, along with dehydration and severe electrolyte imbalance. He was diagnosed with CLD first at 6-month age, and then the other one was also diagnosed with CLD.