Magdalena Sanz Cortes

Fetoscopic Open Neural Tube Defect Repair: Development and Refinement of a Two-port, Carbon Dioxide Insufflation Technique

OBJECTIVE To describe development of a two-port fetoscopic technique for spina bifida repair in the exteriorized, carbon dioxide-filled uterus and report early results of two cohorts of patients: the first 15 treated with an iterative technique and the latter 13 with a standardized technique. METHODS This was a retrospective cohort study (2014-2016). All patients met Management of Myelomeningocele Study selection criteria. The intraoperative approach was iterative in the first 15 patients and was then standardized. Obstetric, maternal, fetal, and early neonatal outcomes were compared. Standard parametric and nonparametric tests were used as appropriate. RESULTS Data for 28 patients (22 endoscopic only, four hybrid, two abandoned) are reported, but only those with a complete fetoscopic repair were analyzed (iterative technique [n=10] compared with standardized technique [n=12]). Maternal demographics and gestational age (median [range]) at fetal surgery (25.4 [22.9-25.9] compared with 24.8 [24-25.6] weeks) were similar, but delivery occurred at 35.9 (26-39) weeks of gestation with the iterative technique compared with 39 (35.9-40) weeks of gestation with the standardized technique (P<.01). Duration of surgery (267 [107-434] compared with 246 [206-333] minutes), complication rates, preterm prelabor rupture of membranes rates (4/12 [33%] compared with 1/10 [10%]), and vaginal delivery rates (5/12 [42%] compared with 6/10 [60%]) were not statistically different in the iterative and standardized techniques, respectively. In 6 of 12 (50%) compared with 1 of 10 (10%), respectively (P=.07), there was leakage of cerebrospinal fluid from the repair site at birth. Management of Myelomeningocele Study criteria for hydrocephalus-death at discharge were met in 9 of 12 (75%) and 3 of 10 (30%), respectively, and 7 of 12 (58%) compared with 2 of 10 (20%) have been treated for hydrocephalus to date. These latter differences were not statistically significant. CONCLUSION Fetoscopic open neural tube defect repair does not appear to increase maternal-fetal complications as compared with repair by hysterotomy, allows for vaginal delivery, and may reduce long-term maternal risks. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov, https://clinicaltrials.gov, NCT02230072.

Clinical assessment and brain findings in a cohort of mothers, fetuses and infants infected with ZIKA virus

BACKGROUND: Congenital Zika virus (ZIKV) infection can be detected in both the presence and absence of microcephaly and manifests as a number of signs and symptoms that are detected clinically and by neuroimaging. However, to date, qualitative and quantitative measures for the purpose of diagnosis and prognosis are limited. OBJECTIVES: Main objectives of this study conducted on fetuses and infants with confirmed congenital Zika virus infection and detected brain abnormalities were (1) to assess the prevalence of microcephaly and the frequency of the anomalies that include a detailed description based on ultrasound and magnetic resonance imaging in fetuses and ultrasound, magnetic resonance imaging, and computed tomography imaging postnatally, (2) to provide quantitative measures of fetal and infant brain findings by magnetic resonance imaging with the use of volumetric analyses and diffusion‐weighted imaging, and (3) to obtain additional information from placental and fetal histopathologic assessments and postnatal clinical evaluations. STUDY DESIGN: This is a longitudinal cohort study of Zika virus–infected pregnancies from a single institution in Colombia. Clinical and imaging findings of patients with laboratory‐confirmed Zika virus infection and fetal brain anomalies were the focus of this study. Patients underwent monthly fetal ultrasound scans, neurosonography, and a fetal magnetic resonance imaging. Postnatally, infant brain assessment was offered by the use of ultrasound imaging, magnetic resonance imaging, and/or computed tomography. Fetal head circumference measurements were compared with different reference ranges with <2 or <3 standard deviations below the mean for the diagnosis of microcephaly. Fetal and infant magnetic resonance imaging images were processed to obtain a quantitative brain volumetric assessment. Diffusion weighted imaging sequences were processed to assess brain microstructure. Anthropometric, neurologic, auditory, and visual assessments were performed postnatally. Histopathologic assessment was included if patients opted for pregnancy termination. RESULTS: All women (n=214) had been referred for Zika virus symptoms during pregnancy that affected themselves or their partners or if fetal anomalies that are compatible with congenital Zika virus syndrome were detected. A total of 12 pregnant patients with laboratory confirmation of Zika virus infection were diagnosed with fetal brain malformations. Most common findings that were assessed by prenatal and postnatal imaging were brain volume loss (92%), calcifications (92%), callosal anomalies (100%), cortical malformations (89%), and ventriculomegaly (92%). Results from fetal brain volumetric assessment by magnetic resonance imaging showed that 1 of the most common findings associated with microcephaly was reduced supratentorial brain parenchyma and increased subarachnoid cerebrospinal fluid. Diffusion weighted imaging analyses of apparent diffusion coefficient values showed microstructural changes. Microcephaly was present in 33.3–58.3% of the cases at referral and was present at delivery in 55.6–77.8% of cases. At birth, most of the affected neonates (55.6–77.8%) had head circumference measurements >3 standard deviations below the mean. Postnatal imaging studies confirmed brain malformations that were detected prenatally. Auditory screening results were normal in 2 cases that were assessed. Visual screening showed different anomalies in 2 of the 3 cases that were examined. Pathologic results that were obtained from 2 of the 3 cases who opted for termination showed similar signs of abnormalities in the central nervous system and placental analyses, including brain microcalcifications. CONCLUSION: Congenital microcephaly is not an optimal screening method for congenital Zika virus syndrome, because it may not accompany other evident and preceding brain findings; microcephaly could be an endpoint of the disease that results from progressive changes that are related to brain volume loss. Long‐term studies are needed to understand the clinical and developmental relevance of these findings.

Are First Trimester Nuchal Septations Independent Risk Factors for Chromosomal Anomalies

There is conflicting information regarding the role of nuchal septations during first‐trimester genetic screening. This study was designed to determine whether nuchal septations are risk factors for chromosomal anomalies, independent of increased nuchal translucency (NT), in the first trimester of pregnancy.

Unusual course of hyperreactio luteinalis in twin pregnancy complicated by twin to twin transfusion syndrome

We report the case of 35-year-old female patient G0P1 with spontaneous twin pregnancy who presented to our fetal center with the suspicion of twin to twin syndrome (TTTS). Upon evaluation, a diagnosis of selective fetal growth restriction type III (intermittent absent/reversed end-diastolic flow in the umbilical arteries) at 16 weeks and 6 days was made. Following counseling, the parents opted for expectant management.

Chronic Maternal Hyperoxygenation and Effect on Cerebral and Placental Vasoregulation and Neurodevelopment in Fetuses with Left Heart Hypoplasia

Introduction: In a pilot study of chronic maternal hyperoxygenation (CMH) in left heart hypoplasia (LHH), we sought to determine effect estimates of CMH on head size, vascular resistance indices, and neurodevelopment compared to controls. Material and Methods: Nine gravidae meeting the inclusion criteria (fetal LHH, ≥25.9 weeks’ gestation, and ≥10% increase in percent aortic flow after acute hyperoxygenation) were prospectively enrolled. Controls were 9 contemporary gravidae with fetal LHH without CMH. Brain growth and Doppler-derived estimates of fetal cerebrovascular and placental resistance were blindly evaluated and compared using longitudinal regression. Postnatal anthropomorphic and neurodevelopmental assessments were compared. Results: There was no difference in baseline fetal measures between groups. There was significantly slower biparietal diameter (BPD) growth in the CMH group (z-score change –0.03 ± 0.02 vs. +0.09 ± 0.05 units/week, p = 0.02). At 6 months postnatal age, the mean head circumference z-score in the CMH group was smaller than that of controls (–0.20 ± 0.58 vs. +0.85 ± 1.11, p = 0.048). There were no differences in neurodevelopmental testing at 6 and 12 months. Discussion: In this pilot study, relatively diminished fetal BPD growth and smaller infant head circumference z-scores at 6 months were noted with in utero CMH exposure.

Contemporary Modalities to Image the Fetal Brain

Fetal brain ultrasound remains as the mainstay for screening fetal intracranial anatomy. One of its main advantages is the availability of 3 dimensional and other ultrasound modalities for a better understanding of fetal neurodevelopment. Neurosonography is performed when findings, suggestive of an abnormality, are present on a screening ultrasound or if a high-risk situation of brain injury is present. This technique offers the use of complementary imaging planes, axial, coronal and sagittal, and the ability to image intracranial anatomy from the transabdominal and transvaginal approaches. Fetal brain magnetic resonance imaging is more sensitive than ultrasound. As an adjunctive imaging modality, magnetic resonance imaging offers additional sequences to complete the information on neurodevelopment from different perspectives, such as brain metabolism, microstructure, and connectivity.