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OBJECTIVE: To assess the safety of Partial-Amniotic-Insufflation-of-heated-humidified-CO2 (hPACI) during fetoscopic spina bifida repair (fSB-repair). METHOD: A simulated fSB-repair through an exteriorized uterus under hPACI was performed in 100-day fetal lambs (term = 145 days) under a laboratory anesthesia protocol (n = 5; group 1) which is known to induce maternal-fetal acidosis and hypercapnia. Since these may not occur clinically, we applied a clinical anesthesia protocol (n = 5; group 2), keeping maternal parameters within physiological conditions, that is, controlled maternal arterial carbon dioxide (CO2) pressure (pCO2 = 30 mmHg), blood pressure (≥67 mmHg), and temperature (37.1-39.8°C). Our superiority study used fetal pH as the primary outcome. RESULTS: Compared to group 1, controlled anesthesia normalized fetal pH (7.23 ± 0.02 vs. 7.36 ± 0.02, p

Objective: To determine the long-term maternal impact of open fetal spina bifida repair. Design: Prospective cohort study. Setting: University Hospitals Leuven, Belgium. Population: Hundred consecutive mothers who had open maternal-fetal spina bifida repair between 2012-2022. Methods: A patient-reported survey on subsequent fertility, pregnancy, gynaecological and psychological outcomes. Main Outcome Measures: Complications during subsequent pregnancies, gynaecological and psychological problems. Results: Seventy-two out of 100 invited women completed the questionnaire (72%). Despite being advised not to, 7/13 of women attempting to conceive, did so within two years after fetal surgery and one delivered vaginally. Two of the 16 subsequent pregnancies were complicated by an open neural tube defect. One pregnancy was complicated by a placenta accreta, and one by a uterine rupture, both with good neonatal outcome. Nearly half of respondents who did not attempt to conceive, reported that this was due to the experience during the index pregnancy and care for the index child. Three out of four respondents reported long-term psychological problems, mostly anxiety for the health of the index child, fear for recurrence in subsequent pregnancies and feelings of guilt. Conclusions: Open maternal-fetal surgery for spina bifida did not appear to affect fertility in our cohort. Half of the attempts to conceive took place within two years. One uterine rupture and one placenta accreta occurred in 16 subsequent pregnancies. Most respondents reported psychological problems linked to the index pregnancy, which reinforces the need for long-term psychological support. Funding: Great Ormond Street Hospital Children’s Charity, FWO-Flanders, Klinisch Onderzoeksfonds UZ Leuven.

OBJECTIVE: To determine the incidence and characterise corpus callosum (CC) abnormalities in fetuses with spina bifida aperta (SBA) between 18 and 26 weeks of gestation. METHODS: This was a retrospective study on fetuses with isolated SBA and who were assessed for fetal surgery. Digitally stored ultrasound images of the brain were reviewed for the presence/absence of the CC, and the length and diameter of its constituent parts (rostrum, genu, body and splenium). We used regression analysis to determine the relationship between CC abnormalities and gestational age, head circumference, ventricle size, lesion level and lesion type. RESULTS: Nearly three-quarters of fetuses with isolated SBA had an abnormal CC (71.7%, 76/106). Partial agenesis was most common in the splenium (18.9%, 20/ 106) and the rostrum (13.2%, 14/106). The most common abnormal pattern was of a short CC with normal diameter throughout. Of note, 20.8% (22/106) had a hypoplastic genu and 28.3% (30/106) had a thick body part. Larger lateral ventricle size was associated with partial agenesis of the CC (odds ratio [OR]: 0.14, p < 0.001) and inversely associated with a shorter CC (OR: 2.60, p < 0.01). CONCLUSION: An abnormal CC is common in fetuses with isolated SBA who are referred for fetal surgery.

BACKGROUND: Congenital diaphragmatic hernia (CDH) reportedly has neurologic consequences in childhood however little is known about the impact in isolated CDH. AIMS: Herein we aimed to describe the risk of neurodevelopmental complications in children born with isolated CDH. MATERIALS & METHODS: We systematically reviewed literature for reports on the neurological outcome of infants born with isolated CDH. The primary outcome was neurodevelopmental delay. Secondary outcomes included, motor skills, intelligence, vision, hearing, language and behavior abnormalities. RESULTS: Thirteen out of 87 (15%) studies reported on isolated CDH, including 2624 out of 24,146 children. Neurodevelopmental delay was investigated in four studies and found to be present in 16% (3-34%) of children. This was mainly attributed to motor problems in 13% (2-30%), whereas cognitive dysfunction only in 5% (0-20%) and hearing in 3% (1-7%). One study assessed the effect of fetal surgery. When both isolated and non-isolated children were included, these numbers were higher. DISCUSSION: This systematic review demonstrates that only a minority of studies focused on isolated CDH, with neurodevelopmental delay present in 16% of children born with CDH. CONCLUSION: To accurately counsel patients, more research should focus on isolated CDH cases and examine children that underwent fetal surgery. ispartof: PRENATAL DIAGNOSIS vol:42 issue:3 pages:318-329 ispartof: location:England status: published

Background Abnormal intracranial findings are often detected at mid‐trimester ultrasound (US) in fetuses with myelomeningocele (MMC). It is unclear whether these findings constitute a spectrum of the disease or are an independent finding, which should contraindicate fetal surgery. Objective To ascertain the spectrum and frequency of US‐detected cranial findings in fetuses with MMC. Search strategy MEDLINE, Embase, Web of Science and CENTRAL were searched from January 2000 to June 2020. Selection criteria Study reporting incidence of cranial US findings in consecutive cases of second‐trimester fetuses with MMC. Data collection and analysis Publication quality was assessed by Newcastle–Ottawa Scale (NOS) and modified NOS. Meta‐analysis could not be performed as a result of high clinical diversity and study heterogeneity. Main results Fourteen cranial US findings were reported in 15 studies. Findings in classic Chiari II malformation (CIIM) spectrum included posterior fossa funnelling (96%), small transcerebellar diameter (82–96%), ‘banana’ sign (50–100%), beaked tectum (65%) and ‘lemon’ sign (53–100%). Additional cranial findings were small biparietal diameter (BPD) and head circumference (HC) (, Tweetable abstract A high rate of cranial abnormalities found on second‐trimester ultrasound in fetuses with myelomeningocele.

OBJECTIVE: Widely accepted, validated and objective measures of ultrasound competency have not been established for clinical practice. Outcomes of training curricula are often based on arbitrary thresholds, such as the number of clinical cases completed. We aimed to define metrics against which competency could be measured. METHOD: We undertook a prospective, observational study of obstetric sonographers at a UK University Teaching Hospital. Participants were either experienced in fetal ultrasound (n = 10, >200 ultrasound examinations) or novice operators (n = 10

OBJECTIVE: We performed a systematic review to summarize the efficacy and safety of in utero stem cells application in preclinical models with myelomeningocele (MMC). METHODS: The study was registered with PROSPERO (CRD42019160399). We searched MEDLINE, Embase, Web of Science, Scopus and CENTRAL for publications articles on stem cell therapy in animal fetuses with MMC until May 2020. Publication quality was assessed by the SYRCLE's tool. Meta-analyses were pooled if studies were done in the same animal model providing similar type of stem cell used and outcome measurements. Narrative synthesis was performed for studies that could not be pooled. RESULTS: Nineteen and seven studies were included in narrative and quantitative syntheses, respectively. Most used mesenchymal stem cells (MSCs) and primarily involved ovine and rodent models. Both intra-amniotic injection of allogeneic amniotic fluid (AF)-MSCs in rat MMC model and the application of human placental (P)-MSCs to the spinal cord during fetal surgery in MMC ovine model did not compromise fetal survival rates at term (rat model, relative risk [RR] 1.03, 95% CI 0.92-1.16; ovine model, RR 0.94, 95% CI 0.78-1.13). A single intra-amniotic injection of allogeneic AF-MSCs into rat MMC model was associated with a higher rate of complete defect coverage compared to saline injection (RR 16.35, 95% CI 3.27-81.79). The incorporation of human P-MSCs as a therapeutic adjunct to fetal surgery in the ovine MMC model significantly improved sheep locomotor rating scale after birth (mean difference 5.18, 95% CI 3.36-6.99). CONCLUSIONS: Stem cell application during prenatal period in preclinical animal models is safe and effective. ispartof: PRENATAL DIAGNOSIS vol:41 issue:3 pages:283-300 ispartof: location:England status: published

Objectives Cervical cerclage is used to manage women at high risk of late miscarriage (LM) and spontaneous preterm birth (PTB) due to factors such as history of cervical insufficiency (CI), uterine anomaly, cervical surgery and ultrasound (US) diagnosed cervical shortening. Urinary tract infection (UTI) and subsequent pyelonephritis, and bacterial infection are associated with PTB, but their role in PTB after cervical cerclage is unknown. We examined the relationship between UTI and bacterial vaginosis (BV), fetal fibronectin (fFN) test and PTB in women undergoing elective- or US-indicated cervical cerclage. We also investigated whether fetal fibronectin (fFN) test were useful to predict PTB. Study design This is a single center, retrospective study of singleton pregnant women at PTB clinic, University College London Hospital (UCLH, 2005–2015) who underwent elective or US-indicated cervical cerclage. Women were tested for UTI and BV before cerclage placement and received mid-gestation fFN testing. Patient data were extracted from the PTB clinic database and electronic records. Statistical analyses used Pearson’s chi-square and Mann-Whitney U tests. P values were corrected by Bonferroni method as required. Results 267 singleton pregnant women attended our clinic with completed birth outcome. Of those, 32.2% (86/267) delivered prematurely. All women with UTI or BV received antibiotic treatment. Women with a UTI before cerclage placement were more likely to deliver preterm when compared to those with negative MSU culture (OR 3.39, 95%CI 1.24-9.27, p = 0.04). Their gestational age at delivery were also lower than those with negative MSU result (36+6, IQR 31+4-38+2week vs 38+1, IQR 36+1-39+5-week, p = 0.05). However, UTI after cerclage placement or BV either before or after cerclage placement were not associated with PTB. Women who had a positive fFN result were more likely to deliver preterm (OR 3.85, 95% CI 1.81–8.41, p = 0.0007). Conclusions The presence of a UTI before cervical cerclage is associated with a higher rate of PTB in women who receive a cervical cerclage, even when treated. We did not find an association between pre or post-cerclage BV or post-cerclage UTI and PTB. Further research is needed to elucidate the link between UTI and PTB in women undergoing cervical cerclage.

Many percutaneous needle-based procedures such as foetal interventions, tumor biopsies, nerve blocks, and central venous catheterizations are guided by ultrasound (US) imaging to identify the procedural target and to visualize the needle. A key challenge associated with ultrasound-guided needle insertions is accurate and efficient identification of the needle tip, as thin needles can readily stray from the imaging plane and can have poor visibility at large insertion angles. Ultrasonic tracking is a method for localising the needle tip relative to the imaging plane in real-time, using an ultrasonic transmitter or receiver integrated into the needle that is in communication with an external ultrasound imaging probe. This study had two foci. The first was to increase the sensitivity with which ultrasound reception was performed, using a custom fiber optic hydrophone with a high-finesse Fabry-Perot cavity based ultrasound sensor. This sensor, which comprised of a polymer layer sandwiched between dielectric mirrors, was interrogated continuously during insertions into tissue. The second focus of the study was to develop a custom needle stylet into which the fiber optic hydrophone was integrated, which was fully compatible with clinical practice and which could be adapted to different needles. We tested the sensitivity of the sensorized stylet across a wide range of needle angulations, depths and insertion angles in different biological tissues. We demonstrated, for the first time, needle tip localization in ex-vivo tissues at depths beyond 6 cm and insertion angles steeper than 80°. We conclude that ultrasonic tracking with high-finesse Fabry-Perot fiber optic hydrophone is very promising for use in clinical practice.

Background: The primary objective of this study was to assess the proportion of malignancies in ovarian masses during 1 st January 2002, to 31 st December 2011 at the Department of Obstetrics and Gynecology, King Chulalongkorn Memorial Hospital. A secondary objective was to evaluate associations with patients’ clinical characteristics and ovarian malignancy proportion and subtypes. Materials and Methods: Retrospective descriptive study analyzed data of ovarian masses larger than 3 centimeters in maximal diameter, from the division of Gynecologic Cyto-Pathology at KCMH. SPSS software version 17 (SPSS, Inc, Chicago, IL, USA) was used. Results: A total number of 6,115 patients were included. Among the total ovarian masses studied, 13.7% were malignant. After the age of sixty, the proportion reached almost 40%. It was also above 20% in women younger than 20 years old. During premenarche period, proportion of ovarian malignancies was 50%. Only 1% of ovarian masses were found to be malignant during the pregnancy and post-partum periods. Parity decreasedthe probability of ovarian malignancy during postmenopausal years. Period of menopause did not have any impact on this probability. During the first two decades of life, germ cell malignancy dominated. As the age increased, the percentage of surface epithelial-stromal malignancy increased with a peak at the fifth decade. In contrast, malignant sex cord-stromal cell tumors occurred at a constant rate in each age group after the thirties. Conclusions: Proportion of ovarian cancers in each age group, menstrual and pregnancy status are similar. However there are differences in the distribution of ovarian subtypes especially for the surface epithelialstromal category.