Prenatal Diagnosis and Outcomes of Cervical Meningocele and Myelomeningocele.

Prenatal diagnosis of myelomeningocele remains challenging for obstetricians, ultrasonographers, and radiologists, although the increased maternal serum alpha-fetoprotein level aids in the confirmative diagnosis. Fetal cervical myelomeningocele and meningocele are very rare and unique types of myelomeningocele. Prenatal diagnosis of cervical myelomeningocele and meningocele should include the differential diagnosis and association of many intracranial and spino-skeletal pathogenetic variants and genetic diseases, including subependymal nodular heterotopia and Klippel-Feil syndrome. In this report, a comprehensive review of fetal cervical myelomeningocele with its prenatal diagnosis and long-term outcomes is presented.

The neural basis of pain during labor.

Characterizing a labor pain-related neural signature is a key prerequisite for devising optimized pharmacologic and nonpharmacologic labor pain relief methods. The aim of this study was to describe the neural basis of labor pain and to provide a brief summary of how epidural anesthesia may affect pain-related neuronal activity during labor. Possible future directions are also highlighted. By taking advantage of functional magnetic resonance imaging, brain activation maps and functional neural networks of women during labor that have been recently characterized were compared between pregnant women who received epidural anesthesia and those who did not. In the subgroup of women who did not receive epidural anesthesia, labor-related pain elicited activations in a distributed brain network that included regions within the primary somatosensory cortex (postcentral gyrus and left parietal operculum cortex) and within the traditional pain network (lentiform nucleus, insula, and anterior cingulate gyrus). The activation maps of women who had been administered epidural anesthesia were found to be different-especially with respect to the postcentral gyrus, the insula, and the anterior cingulate gyrus. Parturients who received epidural anesthesia were also compared with those who did not in terms of functional connectivity from selected sensory and affective regions. When analyzing women who did not receive epidural anesthesia, marked bilateral connections from the postcentral gyrus to the superior parietal lobule, supplementary motor area, precentral gyrus, and the right anterior supramarginal gyrus were observed. In contrast, women who received epidural anesthesia showed fewer connections from the postcentral gyrus-being limited to the superior parietal lobule and supplementary motor area. Importantly, one of the most noticeable effects of epidural anesthesia was observed in the anterior cingulate cortex-a primary region that modulates pain perception. The increased outgoing connectivity from the anterior cingulate cortex in women who received epidural anesthesia indicates that the cognitive control exerted by this area might play a major role in the relief from labor pain. These findings not only affirmed the existence of a brain signature for pain experienced during labor, but they also showed that this signature can be altered by the administration of epidural anesthesia. This finding raises a question about the extent to which the cingulo-frontal cortex may exert top-down influences to gate women's experiences of labor-related pain. Because the anterior cingulate cortex is also involved in the processing and modulation of emotional content, such as fear and anxiety, a related question is about the extent to which the use of epidural anesthesia can affect different components of pain perception. Finally, inhibition of anterior cingulate cortex neurons may represent a potential new therapeutic target for alleviating labor-associated pain.

Birth outcomes following pelvic ring injury: A retrospective study.

OBJECTIVE: To report obstetric outcomes in pregnant women with previous pelvic ring injury (PRI) and investigate the correlation between residual pelvic deformity and the mode of delivery. DESIGN: Retrospective cohort study. SETTING: Single medical centre in Taiwan. POPULATION: Forty-one women with PRI histories from 2000 to 2021 who subsequently underwent pregnancy and delivery. METHODS: All patients had complete PRI treatment and radiological follow up for at least 1 year. The demographic data, radiological outcomes after PRI and obstetric outcomes were collected to investigate the potential factors of delivery modes using non-parametric approaches and logistic regression. Caesarean section (CS) rates among different subgroups were reported. MAIN OUTCOME MEASURES: Comparisons of demographic data and radiological outcomes (Matta/Tornetta criteria and Lefaivre criteria) after PRI among patients who had subsequent pregnancy and underwent vaginal deliveries (VD) or CS. RESULTS: There were 14 VD and 27 CS in 41 patients. Nine patients underwent CS because of their PRI history, 12 patients underwent CS for other obstetric indications and 20 underwent trial of labour. Based on the logistic regression model, retained trans-iliosacral implants did not significantly increase the risk of CS (odds ratio [OR] 1.20; 95% CI 0.17-8.38). Higher pelvic asymmetry value by Lefaivre criteria was a potential risk factor for CS after previous PRI (OR 1.52; 95% CI 1.043-2.213). CONCLUSIONS: VD is possible after PRI. Retained trans-iliosacral implants do not affect the delivery outcome. Residual pelvic asymmetry after PRI by Lefaivre criteria is a potential risk factor for CS.

Incidence, prognosis, and perinatal outcomes of and risk factors for severe twin-twin transfusion syndrome with right ventricular outflow tract obstruction in the recipient twin after fetoscopic laser photocoagulation.

BACKGROUND: Right ventricular outflow tract obstruction (RVOTO) is the most frequently encountered congenital heart disease in patients with twin -twin transfusion syndrome (TTTS) and is especially prevalent in the recipient twin. In this retrospective study, we evaluated the incidence, prognosis, postnatal management, and perinatal outcomes of and risk factors for RVOTO in the recipient twin in severe TTTS cases which diagnosed before 26 weeks after fetoscopic laser photocoagulation (FLP) at a single center in Taiwan. METHODS: RVOTO was diagnosed using fetal or postnatal echocardiography. The fetal outcomes evaluated were perinatal survival rate, neonatal brain image anomalies rate, gestational age at delivery, and birth weight. RESULTS: Total 187 severe TTTS cases were included; 14 (7.49%) had a recipient twin with RVOTO (12 cases of pulmonary stenosis and 2 of pulmonary atresia). Of these 14 cases, 3 (21.4%) demonstrated improvements in outflow obstruction after FLP, and 11 (78.6%) resulted in perinatal survival. Of the 11 survivors, 5 (45.5%) received transcatheter balloon valvuloplasty to alleviate the RVOTO. The perinatal survival rate, gestational age at delivery, neonatal brain image anomaly rate, and birth weights did not significantly differ between the groups in which the recipient twin had versus did not have RVOTO. Generally, the recipient twin had RVOTO received FLP at a younger gestational age (in weeks; 19.3 ± 2.4 vs. 20.7 ± 2.6, p = 0.048) and had a higher percentage of cases at Quintero stage IV (50.0% vs. 12.1%, p < 0.001) than those in which the recipient twin did not have with RVOTO. Using logistic regression, we discovered that FLP at a younger gestational age (p = 0.046, odds ratio = 0.779) and TTTS at Quintero stage IV (p = 0.001, odds ratio = 7.206) were risk factors for the recipient twin developing RVOTO after FLP in severe TTTS cases. CONCLUSIONS: The post-FLP perinatal outcomes of cases of severe TTTS in which the recipient twin had versus did not have RVOTO were comparable in this study, which may have been due to the similar gestational ages at delivery and strong influence of high Quintero stages (stages III and IV).

Synchronous/metachronous endometrial and colorectal malignancies in Taiwanese women: a population-based nationwide study.

INTRODUCTION: Endometrial cancer (EC) and colorectal cancer (CRC) may share a common genetic background. In a subset of patients, the two malignancies can coexist either at the time of diagnosis (synchronous) or develop consequently (metachronous). The purpose of this nationwide, population-based study was to investigate the occurrence and clinical outcomes of synchronous/metachronous EC/CRC in Taiwanese women. MATERIALS AND METHODS: Data for women diagnosed with EC and/or CRC between 2007 and 2015 were retrospectively retrieved from the nationwide Taiwan Cancer Registry. Mortality data were obtained from the National Death Registry. Women with synchronous/metachronous EC/CRC versus EC or CRC were compared in terms of clinical characteristics and outcomes. RESULTS: Of the 62,764 Taiwanese women diagnosed with EC and/or CRC during the study period, 167 (0.3%) had synchronous/metachronous EC/CRC. Among them, 72 cases (43.1%) presented with EC followed by CRC, 66 (39.5%) with CRC followed by EC, and 29 (17.4%) with synchronous EC/CRC. Kaplan-Meier estimates for time-to-event data revealed that the 2-year risk rates of developing a metachronous tumor of interest (CRC or EC) in women diagnosed with an initial EC and CRC were 39.6% and 42.1%, respectively. The 5-year overall survival rates of women with metachronous EC/CRC who had an initial diagnosis of EC, CRC, and synchronous EC/CRC were 73.9%, 70.9%, and 37.0%, respectively. CONCLUSIONS: Endometrial cancer is the most common first tumor in Taiwanese women with metachronous EC/CRC. The 2-year risk rates of developing a metachronous tumor of interest (CRC or EC) in women diagnosed with an initial EC and CRC are not negligible. Surveillance for CRC is recommended for all women diagnosed with EC. The clinical outcomes of synchronous EC/CRC are markedly less favorable.

Streptococcus vaginalis sp. nov., a novel bacterial species isolated from vaginal swabs of a pregnant woman with diabetes.

Sequences targeted at the V3 and V4 16S rRNA hypervariable regions of a streptococcal strain (P1L01T) isolated from vaginal swabs of a pregnant woman with diabetes were 100% similar to those of Streptococcus anginosus subsp. whileyi. However, phylogenetic analysis based on 16S rRNA full-gene sequencing (1562 bp) revealed highest sequence similarity to Streptococcus periodonticum (98.7%), followed by Streptococcus anginosus subsp. whileyi (98.7%), and Streptococcus anginosus subsp. anginosus (98.4%). Phylogenies of housekeeping genes rpoB and groEL were compared to improve classification, and the results showed a clear separation between strain P1L01T and closely related Streptococcus type strains. The complete genome of strain P1L01T consisted of 2,108,769 bp with a G + C content of 38.5 mol%. Average nucleotide identity values, based on genome sequencing, between strain P1L01T and Streptococcus periodonticum KCOM 2412T, Streptococcus anginosus subsp. whileyi CCUG 39159T, and Streptococcus anginosus subsp. anginosus NCTC 10713T were 95.5%, 94.3%, and 95.3%, respectively. The highest in silico DNA-DNA hybridization value with respect to the closest species was 66.2%, i.e., below the species cutoff of 70% hybridization. The main cellular fatty acids of strain P1L01T were 16:0, 18:1ω7c, and 14:0. On the basis of phylogenetic, genotypic and phenotypic data, we propose to classify this isolate as representative of a novel species of the genus Streptococcus, Streptococcus vaginalis sp. nov., in reference to its isolation from vaginal swabs, with strain P1L01T (= NBRC 114754T = BCRC 81289T) as the type strain.

DNA methylation marker for the triage of hrHPV positive women in cervical cancer screening: Real-world evidence in Taiwan.

OBJECTIVE: Human papillomavirus (HPV) testing as the primary cervical cancer screening followed by reflex cytology if high-risk HPV is present (hrHPV+) is recently adopted in some countries. However, reflex cytology's sensitivity is variable, and a suitable triage approach for hrHPV+ remains controversial. Here, we compared the performance of three triage tools in hrHPV+ women. METHODS: Three triage tools-cytology, HPV16/18 genotyping, and DNA methylation biomarker PAX1m-were analyzed for their clinical performance in hrHPV+ women. In addition, women without cervical cancer at enrollment were followed for histologically confirmed high-grade cervical intraepithelial neoplasia or worse (CIN3+) annually using Papanicolaou smear. RESULTS: Of 4762 women aged ≥20 years enrolled, 502 (10.5%) were hrHPV+. PAX1m and cytology demonstrated similar accuracy (>90%), sensitivity (>78%), and specificity (>92%) as triage tools in 429 hrHPV+ women aged 30-64 years. PAX1m had better accuracy and specificity (91.6% and 92.5%, respectively) than HPV16/18 (76.9% and 76.8%, respectively). The incidence of CIN3+ among hrHPV+ women was 10.7 cases/1000 person-years. The incidence was significantly greater in PAX1m-positive women than in PAX1m-negative women. CONCLUSIONS: PAX1m has comparable clinical performance to cytology and better accuracy and specificity than HPV16/18 as the triage tool for detecting CIN3+ in hrHPV+ women. The PAX1m assay is thus a promising molecular-based triage tool for early detection of CIN and predicting disease progression in hrHPV+ women. It can be especially useful in countries where adequate cytology-based infrastructure is lacking, such as some Southeast Asian countries, for cervical cancer screening and prevention.

Placental glucose transporter 1 and 3 gene expression in Monochorionic twin pregnancies with selective fetal growth restriction.

BACKGROUND: In monochorionic twin (MC) gestations with selective fetal growth restriction (FGR), the discordant fetal growth usually is due to unequal placental sharing. Glucose, which is essential for oxidative metabolism in the growing placenta and fetus, is transferred from maternal blood by facilitated carrier-mediated diffusion via glucose transporters (GLUTs). How the GLUTs expression varies in the two placenta territories manifests discordant perfusion in MC twin pregnancy with selective FGR is unknown. This study evaluates the human placental GLUT1 and GLUT3 gene expression in MC twin gestations with selective FGR. METHODS: MC twin pregnancy with selective FGR was defined as the presence of inter-twin birth weight discordance of > 25% and the smaller twin with a birth weight less than the 10th percentile in third trimester. Fetal umbilical artery Doppler was checked within 1 week before delivery in the two fetuses. An abnormal umbilical artery Doppler was defined as persistently absent or reverse end-diastolic flow (UA-AREDF). GLUT1, GLUT3 and HIF-1α gene expression were assayed in each twin's placental territories. The inter-twin placental gene expression ratio was calculated as the placenta GLUTs or HIF-1α expression level of the selective FGR twin divided by expression level of the appropriate-for-gestational-age (AGA) cotwin. Higher gene expression ratio means elevated gene expression in the selective FGR twin's placenta territory compared to AGA twin's placenta territory. RESULTS: 15 MC twin gestations with selective FGR including nine with normal (group 1) and six with abnormal selective FGR twin UA Doppler (group 2) were included into this study. The GLUT3 and HIF-1α gene expression are significantly elevated in selective FGR twin's placenta territory in group 2 twin pregnancies (mean gene expression ratio as 2.23 and 1.65, p values as 0.015 and 0.045, respectively), but not in in group 1 twin pregnancies. CONCLUSION: The upregulation of placental GLUT3 gene expression in selective FGR fetus with abnormal UA Doppler may be due to hypo-perfusion which is mediated by up -regulation of HIF-1α gene expression.

Detection and prognostic significance of isolated tumor cells and micrometastases in pelvic lymph nodes of patients with early ovarian clear cell carcinoma.

BACKGROUND/PURPOSE: Ovarian clear cell carcinoma (OCCC) accounts for approximately 18% of all epithelial ovarian malignancies in Taiwan and portends a poor prognosis. Here, we sought to investigate whether immunohistochemistry with an anti-pan-cytokeratin antibody cocktail (AE1/AE3) can be used as an adjunct to hematoxylin and eosin (H&E) staining for improving the detection of isolated tumor cells (ITCs) and micrometastasis to pelvic lymph nodes (LNs). We also assessed whether these lesions may predict disease recurrence. METHODS: Pelvic lymphadenectomy specimens were obtained from 197 patients with stage 1 OCCC who had undergone surgery between 2000 and 2018 from Linkou and Kaohsiung Chang Gung Memorial Hospital. Immunohistochemical staining with AE1/AE3 was applied to a total of 1186 slides. Clusters of metastatic tumor cells, detected immunohistochemically, were classified as ITCs (clusters with diameters of ≤0.2 mm) or micrometastases (tumor cell clusters of >0.2 but ≤2.0 mm). We also assessed the diameter of metastases in patients with positive lymph nodes (stage IIIA1, n = 3, 7 positive nodes). RESULTS: Clusters with a positive AE1/AE3 staining were identified in five (2.53%) of the 197 patients (ITCs, n = 3; micrometastasis, n = 2). Four patients had no evidence of disease recurrence but a patient recurred at follow-up. Metastatic foci of patients with stage IIIA1 disease were all >2.0 mm in size. CONCLUSION: Immunohistochemical staining with AE1/AE3 can identify micrometastasis or ITCs in LNs missed on routine H&E staining. The role of micrometastasis in predicting recurrent OCCC and implementing on treatment strategies requires further investigation.

Comprehensive genomic profiling reveals ubiquitous KRAS mutations and frequent PIK3CA mutations in ovarian seromucinous borderline tumor.

The molecular underpinnings of seromucinous borderline tumor (SMBT) - an uncommon ovarian epithelial neoplasm characterized by association with endometriosis, frequent bilateral ovarian involvement, and occasional progression to invasive carcinoma - remain poorly understood. Here, we sought to comprehensively characterize the mutational landscape of SMBT and elucidate the clonal relationship between bilateral ovarian SMBTs. We also compared the mutational profiles between SMBTs and concurrent invasive carcinomas. Formalin-fixed, paraffin-embedded tissue specimens were retrieved from 28 patients diagnosed with SMBT. Massively parallel sequencing of 409 cancer-related genes was conducted to identify somatic mutations in 33 SMBT samples and four concurrent invasive carcinoma specimens. TERT promoter mutations were assessed by Sanger sequencing, whereas immunohistochemistry was used as a surrogate tool for detecting deletions or epigenetic silencing of relevant tumor suppressor genes. Twenty-six (92.9%) of the 28 patients were diagnosed with stage I SMBTs. Seven (25%) cases showed bilateral ovarian involvement and 13 (46%) had concomitant endometriosis. Concurrent ovarian carcinomas were identified in three patients, whereas one case had a synchronous endometrial carcinoma. Somatic mutations in the KRAS, PIK3CA, and ARID1A genes were identified in 100, 60.7, and 14.3% of SMBT samples, respectively. In contrast, TERT promoter mutations and DNA mismatch repair deficiencies were absent. Sequencing of paired specimens from patients with bilateral SMBT revealed the presence of at least two shared somatic mutations, suggestive of a clonal relationship. Similarly, we identified shared somatic mutations between SMBT samples and concurrent ovarian carcinoma specimens. Taken together, these findings demonstrated a distinct mutational landscape of SMBT in which (1) KRAS is invariably mutated, (2) PIK3CA is frequently mutated, and (3) TERT promoter mutations and DNA mismatch repair deficiencies are absent. Our findings represent the first extensive characterization of this rare ovarian neoplasm, with potential implications for disease classification and molecular diagnostics.

A donor twin discordant with Peters anomaly in a twin-twin transfusion syndrome case: a case report.

BACKGROUND: Peters anomaly is a rare form of anterior segment ocular dysgenesis, the antenatal image of Peters anomaly had not been reported. We herein showcased a discordant finding of Peters anomaly in a monozygotic twin complicated with twin-twin transfusion syndrome (TTTS) and exhibited its antenatal sonographic images, CASE PRESENTATION: A 38-year-old gravida 2 para 1 pregnant woman visited our clinic at the gestational age of 18 weeks where TTTS stage III was diagnosed and the following laser therapy was done successfully. Ten days after the surgery, the follow-up ultrasound detected the opacity of both fetal eyeballs in the donor twin and thus congenital cataract was suspected initially. Then magnetic resonance imaging (MRI) examination was arranged at the gestational age of 23 weeks, and no central nervous system or other anomaly was found. At the 29 weeks of gestation, the opacity of both fetal eyeballs of the donor twin did not clear. The pregnancy resulted in cesarean section at the gestational age of 37 weeks indicated by malpresentation where two male live births were born. Examination under anesthesia was arranged for donor twin after delivery and Peters anomaly was diagnosed based on central corneal opacity with iridocorneal and corneolenticular adhesions. CONCLUSIONS: The prenatal image of Peters anomaly may present as the opacity of the fetal eyeballs similar to congenital cataract. Some cases of the Peters anomaly had been reported with a genetic abnormality, but since our case presented discordant presentation in monozygotic twin pregnancy where both twins are supposed to share the same genetic make-up, therefore other factors that are epigenetic may be held accountable. Nevertheless, a genetic origin of the anomaly in our case cannot be excluded.

Severe pre-eclamptic women with headache: is posterior reversible encephalopathy syndrome an associated concurrent finding?

BACKGROUND: A high incidence of posterior reversible encephalopathy syndrome (PRES) has been observed in women with eclampsia on imaging. However this association was documented mostly after convulsions occurred. This study aimed to detect the development of PRES using magnetic resonance imaging (MRI) in women with severe preeclampsia and headache, and evaluate the clinical and radiological findings in obstetric outcomes. METHODS: A prospective single-center cohort study comprising 20 pregnant women with severe pre-eclampsia related headache was conducted using Numeric Rating Scale (NRS) score of ≧4. Additionally, non-contrast brain MRI was used to detect PRES and related radiological central nervous system (CNS) abnormalities. RESULTS: Patients were enrolled at a mean gestational age of 32 weeks (range 29-38 weeks). Two women were unable to complete the scanning. Of the 18 MRI scans, 15 (83%) revealed abnormal findings. One patient developed an altered mental state and diffuse PRES, with the occipital, temporal, thalamus, and basal ganglia, the brain stem, and the cerebellum being affected. Two patients had abnormal susceptibility-weighted imaging (SWI) findings, indicating micro-hemorrhages. The majority (12 cases, 66%) of the patients had abnormal cortical hyperintensities in the occipital and temporal lobes. Only three patients had normal MRI pictures. None of the women had eclampsia occurred during the peripartum period, and only one unrelated neonatal death due to congenital anomalies. CONCLUSION: A high incidence of abnormal cortical hyperintensity changes at locations typical for PRES on MRI was noted in women with severe pre-eclampsia and headache. These early hypertensive neurological signs allowed prompt and efficient obstetrical management, to prevent the development of eclampsia and PRES.

A Simple Technique for the Placement of Seprafilm, a Sodium Hyaluronate or Carboxymethylcellulose Absorbable Barrier, during Laparoscopic Myomectomy.

This report describes a simple technique using conventional instrumentation for the placement of Seprafilm, a sodium hyaluronate or carboxymethylcellulose absorbable barrier for adhesion prevention. A total of 378 women with uterine myomas undergoing laparoscopic myomectomies had 737 Seprafilm pieces placed. Seprafilm sheet was softened through exposure to room air for 5 minutes, cut into 4 pieces (length, 5-10 mm), rolled up alongside a plastic sheet cut from a camera drape cover, and gently placed at the right paracolic gutter. The Seprafilm pieces unfolded semiautomatically on release and were then placed on the uterus. The median time to apply per Seprafilm piece was 1 (range: 0.8-3.5) minute. We failed to place 16 pieces (16 of 737, 2.2%) in 11 patients. Virginal status, myoma weight, and the number of removed myomas were the risk factors of failed placement. Our technique for Seprafilm placement during laparoscopic myomectomy is simple and safe.

Predisposing factors and neonatal outcomes for twin-twin transfusion syndrome cases developing transient donor hydrops after fetoscopic laser coagulation: a case control study.

BACKGROUND: Transient donor hydrops (TDH) is defined as donor hydrops developed within days after laser therapy for twin-twin transfusion syndrome (TTTS) followed by resolution later. The purpose of this study was to evaluate the incidence, neonatal outcomes and predisposing factors of post laser therapy TDH in severe TTTS. METHODS: A total of 142 patients with severe TTTS who received laser therapy were included into this study. The pre-operative characteristics and neonatal outcomes were compared between TTTS with and without post laser therapy TDH. All live neonates received cranial ultrasound examination after delivery, mild cerebral injury was defined as exhibiting at least one of the following: intraventricular hemorrhage (IVH) grade I and II, lenticulostriate vasculopathy and subependymal pseudocysts; severe cerebral injury comprised at least one among the following: IVH grade III or grade IV, cystic periventriculoleukomalacia (PVL) grade II or more, porencephalic cysts, and ventricular dilatation. Fetal survival was defined as living more than 30 days after delivery.

Effects and outcomes of septostomy in twin-to-twin transfusion syndrome after fetoscopic laser therapy.

BACKGROUND: To evaluate the incidence and outcomes of septostomy in twin-to-twin transfusion syndrome (TTTS) after fetoscopic laser therapy. METHODS: A retrospective analysis of TTTS postlaser septostomy between 2005 and 2018 was performed. Postlaser septostomy was diagnosed using both (1) a free-floating intertwin membrane flap visible on ultrasound examination and (2) the rapid equalization of amniotic fluid maximum vertical pocket in the donor and recipient amniotic sacs observed after laser therapy. Perinatal survival, neonatal brain image anomaly, gestational age at operation and birth, incidence of premature rupture of membranes (PROM) within 3 weeks after operation, pseudoamniotic band syndrome, and cord entanglement were evaluated. RESULTS: In the 159 TTTS cases included, 12 had postlaser septostomy. Relative to the group without septostomy, the septostomy group had a lower total fetal survival rate (54.2% vs 73.6%, p = 0.041), an earlier mean gestational age at delivery (27.8 vs 34.4 weeks, p = 0.009), a higher risk of PROMs within 3 weeks after operation (33.3% vs 5.4%, p = 0.004), a higher cord entanglement rate (16.7% vs 0%, p = 0.005), and a higher brain image anomaly rate (23.0% [3/13] vs 5.0% [11/218], p = 0.035). After considering the severe Quintero stages (stage III and IV), postlaser septostomy was the only variable [p = 0.003, odds ratio = 5.1] to predict neonatal brain image anomaly. Postlaser septostomy combined with severe Quintero stages could predict PROMs within 3 weeks after laser therapy [p = 0.001, odds ratio = 14.1 and p = 0.03, odds ratio = 5.4, respectively] and delivery before the gestational age of 28 weeks [p = 0.017, odds ratio = 4.5 and p = 0.034, odds ratio = 2.3, respectively]. The risk of pseudoamniotic band syndrome was not increased by postlaser septostomy in this case series. CONCLUSIONS: Postlaser septostomy in TTTS was associated with poorer fetal survival and more adverse perinatal outcomes even after considering severe Quintero stages before laser therapy. Efforts should be made to prevent septostomy during laser therapy, and septostomy as the primary method to treat TTTS is not advisable.

Prenatal diagnosis of congenital megalourethra with imperforate anus.

BACKGROUND: Congenital megalourethra is a rare prenatal finding while prenatal diagnosis of imperforate anus poses high challenge. This is the first prenatally ultrasound diagnosed case which had congenital megalourethra and imperforate anus. This case demonstrated the possibility of using the prenatal imaging findings to evaluate the postnatal prognostic outcomes in multi-organ anomalies. CASE: We present a case of congenital megalourethra, diagnosed prenatally at 22 weeks' gestation, in which the penis appeared severe dilated with complete absence of the corpora spongiosa and cavernosa. This case also revealed absence of perianal muscle which was in associated with imperforate anus. Detailed prenatal ultrasonographic findings predicted the high possibility of poor outcome of the fetus in the pulmonary, renal, and sexual functions. CONCLUSION: This case serves to identify not only the marked bilateral hydronephrosis features but also the striking lower urethral malformation with obstruction flow effect of the penis. Indeed we believe this is the first case report of a rare case of fetal megalourethra associated with imperforate anus at early second trimester on ultrasonography imaging.

Placental erythropoietin expression is upregulated in growth-restricted fetuses with abnormal umbilical artery Doppler findings: a case-control study of monochorionic twins.

BACKGROUND: We previously reported that fetal plasma erythropoietin (EPO) concentrations are significantly increased in growth-restricted fetuses with abnormal umbilical artery (UA) Doppler. During hypoxia in an ovine model, the primary site of fetal EPO synthesis was switched from the kidneys to the placenta. Therefore, we designed this study to evaluate human placental EPO gene expression and the correlation to fetal serum EPO concentration in growth-restricted fetuses in a monochorionic (MC) twin model. METHODS: In MC twin pairs, selective intrauterine growth restriction (sIUGR) was defined as the presence of (i) birth weight discordance of > 20% and (ii) a smaller twin with a birth weight less than the 10th percentile. Fetal UA and middle cerebral artery (MCA) Doppler were checked within 1 week before delivery. An abnormal UA Doppler was defined as persistently absent or reverse end-diastolic flow. Cerebroplacental ratio (CPR) was defined as MCA-pulsatility index (PI)/UA-PI. Fetal plasma EPO concentrations were measured in cord blood, and EPO gene expression was assayed in each twin's placental territory. The intertwin plasma EPO ratio was calculated as the cord plasma EPO level of the smaller (or sIUGR) twin divided by the EPO concentration of the larger (or appropriate-for-gestational-age (AGA)) twin, and the intertwin placental EPO gene expression ratio was calculated similarly. RESULTS: Twenty-six MC twins were analyzed, including normal twins (Group 1, n = 9), twins with sIUGR without UA Doppler abnormalities (Group 2, n = 9), and twins with sIUGR and UA Doppler abnormalities (Group 3, n = 8). The CPRs of smaller (sIUGR) fetuses were significantly decreased in Group 3 MC twins (p < 0.001), but not significantly different between Group 1 and Group 2. The highest fetal plasma EPO ratio and placental EPO gene expression ratio were identified in Group 3 MC twins (p < 0.001). The placental EPO gene expression ratios were significantly correlated with the fetal plasma EPO ratios (Pearson's correlation test, p = 0.004). CONCLUSION: This study provides evidence of increased placental EPO expression in MC twin fetuses with sIUGR and abnormal UA Doppler. Future studies are needed to confirm the similar role of placental EPO in severe IUGR singletons.

Effects of inter-twin vascular anastomoses of monochorionic twins with selective intrauterine growth restriction on the contents of placental mitochondria DNA.

BACKGROUND: Placental mitochondrial DNA (mtDNA) has been proposed to be an indicator for placental hypoxia. This study was designed to evaluate the effect of vascular anastomoses between monochorionic (MC) twins on placental mtDNA. METHODS: In this study, twin-twin transfusion syndrome (TTTS) treated with laser therapy and MC twins without TTTS (without laser therapy) resulting in two live babies were included in this study. The placental mtDNA fold changes (FC) between the small and large twins were analyzed using real-time quantitative PCR. TTTS twins with selective intrauterine growth restriction (sIUGR) are categorized as group 1, TTTS without sIUGR as group 2, MC twins without TTTS but with sIUGR as group 3, and MC twins without both TTTS and sIUGR as group 4. RESULTS: There were seven cases in group 1, eight in group 2, 26 in group 3, and 24 in group 4 cases. The placental mtDNA FC were significantly higher in group 1 (1.57 ± 0.9) compared to that of the group 3 (0.86 ± 0.6). CONCLUSION: In MC twin pregnancies with sIUGR, the placental mtDNA FC between the small and large twins are different between cases with and without inter-twin anastomoses. These findings suggest that the inter-twin anastomoses in the MC twins with sIUGR may provide rescue perfusion from the appropriate-for-gestational-age twin to the sIUGR one.

Increased Fetal Plasma Erythropoietin in Monochorionic Twin Pregnancies With Selective Intrauterine Growth Restriction and Abnormal Umbilical Artery Doppler.

Hypoxia is the primary stimulus for the production of erythropoietin (EPO) in both fetal and adult life. Here, we investigated fetal plasma EPO concentrations in monochorionic (MC) twin pregnancies with selective intrauterine growth restriction (sIUGR) and abnormal umbilical artery (UA) Doppler. We diagnosed sIUGR in presence of (1) birth-weight discordance >20% and (2) either twin with a birth weight <10th percentile. An abnormal UA Doppler was defined as a persistent absent-reverse end diastolic flow (AREDF). The intertwin EPO ratio was calculated as the plasma EPO level of the smaller (or small-for-gestational-age) twin divided by the EPO concentration of the larger (or appropriate-for-gestational-age (AGA)) twin. Thirty-two MC twin pairs were included. Of these, 17 pairs were normal twins (Group 1), seven pairs were twins with sIUGR without UA Doppler abnormalities (Group 2), and eight pairs were twins with sIUGR and UA Doppler abnormalities (Group 3). The highest EPO ratio was identified in Group 3 (p < .001) but no significant differences were observed between Groups 1 and 2. Fetal hemoglobin levels did not differ significantly in the three groups, and fetal EPO concentration did not correlate with gestational age at birth. We conclude that fetal plasma EPO concentrations are selectively increased in MC twin pregnancies with sIUGR and abnormal UA Doppler, possibly as a result of uncompensated hypoxia.

Mirror syndrome after fetoscopic laser therapy for twin-twin transfusion syndrome due to transient donor hydrops that resolved before delivery. A case report.

BACKGROUND: Mirror syndrome is a rare complication of twin-twin transfusion syndrome (TTTS). Its clinical picture includes massive edema, oliguria, and hemodilution in the context of fetal hydrops. The occurrence of mirror syndrome after fetoscopic laser therapy for TTTS has been well documented, but resolution of mirror syndrome before delivery has not been reported in the literature. CASE: A 33-year-old woman was referred to our institution at 23(6)/7 weeks' gestation for TTTS, which had been treated with amnioreduction twice: at 21 and 22 gestational weeks, respectively. Mirror syndrome was diagnosed after fetoscopic laser therapy for TTTS at 24 weeks' gestation due to maternal manifestations of pulmonary edema, skin edema, anemia, low blood protein concentration and proteinuria accompanied by donor hydrops. The maternal respiratory symptoms then gradually abated in <2 weeks along with improved fetal condition, resulting in a delivery with favorable outcomes at 36 weeks' gestation. CONCLUSION: Manifestation of mirror syndrome after fetoscopic laser therapy in twin-twin transfusion due to donor hydrops doesn't necessarily predict a poor perinatal outcome.