Mayel Yepez

Serial Head and Brain Imaging of 17 Fetuses With Confirmed Zika Virus Infection in Colombia, South America

OBJECTIVE To evaluate fetal ultrasound and magnetic resonance imaging findings among a series of pregnant women with confirmed Zika virus infection to evaluate the signs of congenital Zika syndrome with respect to timing of infection. METHODS We conducted a retrospective case series of pregnant women referred to two perinatal clinics in Barranquilla and Ibagué, Colombia, who had findings consistent with congenital Zika syndrome and Zika virus infection confirmed in maternal, fetal, or neonatal samples. Serial ultrasound measurements, fetal magnetic resonance imaging results, laboratory results, and perinatal outcomes were evaluated. RESULTS We describe 17 cases of confirmed prenatal maternal Zika virus infection with adverse fetal outcomes. Among the 14 symptomatic women, the median gestational age for maternal Zika virus symptoms was 10 weeks (range 7-14 weeks of gestation). The median time between Zika virus symptom onset and microcephaly (head circumference less than 3 standard deviations below the mean) was 18 weeks (range 15-24 weeks). The earliest fetal head circumference measurement consistent with microcephaly diagnosis was at 24 weeks of gestation. The earliest sign of congenital Zika syndrome was talipes equinovarus, which in two patients was noted first at 19 weeks of gestation. Common findings on fetal magnetic resonance imaging were microcephaly, ventriculomegaly, polymicrogyria, and calcifications. CONCLUSION Our analysis suggests a period of at least 15 weeks between maternal Zika virus infection in pregnancy and development of microcephaly and highlights the importance of serial and detailed neuroimaging.

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.

Oxidative stress biomarkers in endometrial secretions: A comparison between successful and unsuccessful in vitro fertilization cycles

A potential role of oxidative stress has been implicated in the outcome of various steps of assisted reproductive technology (ART). In a prospective cohort study, a total of 100 patients undergoing IVF/ICSI procedure due to male factor infertility were recruited based on the inclusion criteria. In all patients, 1-2ml of endometrial secretions was aspirated prior to embryo transfer. The oxidative stress markers in endometrial secretions, including superoxide dismutase (SOD), catalase (CAT) activities, lipid peroxidation (LPO), total thiol groups (TTG), and total antioxidant power (TAP) were investigated and compared among study groups including term pregnancy, failed IVF cycle, and miscarriage. P<0.05 was considered statistically different. Of the 100 patients, 28 cases (28%) resulted in ongoing pregnancy (biochemical pregnancy followed by clinical pregnancy), 11 cases (11%) resulted in miscarriage, and 61 cases (61%), resulted in failed IVF cycle. SOD, LPO, CAT, and TAP levels in the endometrial secretions of the three groups were statistically different (P-value <0.01, <0.001, <0.001, and <0.001, respectively). TTG levels in endometrial secretion of three groups were not statistically different (P-value=0.837). Our results indicated that higher levels of antioxidants such as SOD, CAT, or TAP, and lower levels of oxidative stress markers such as LPO in the endometrial secretions were associated with successful IVF outcome.

OP11.06: Do placental and amniotic membrane pathological changes occur following open and fetoscopic neural tube defect (NTD) repair?: Short oral presentation abstracts

one showed a fluctuant colour, between bright red and dark purple (bidirectional flow), which is rare in this type of anastomoses that usually have unidirectional flow. Results: In 9 of the 10 cases, there was intrauterine demise of the sick twin within the next 4 weeks after surgery. The changing colour in the AV anastomosis which is supposed to be unidirectional, was due to the low central blood pressure of the premortem small twin which turns into a low vascular pressure in the chorionic arterial branch too low to overcome the pressure of the chorionic vein branch of the normal twin at the level of the AV anastomosis. Conclusions: MCDA twin pregnancies complicated with a severe sFGR type II with no superimposed TTTS and that showed during Fetoscopic surgery a fluctuant change of colour at the level of an AV anastomosis had a high mortality rate of the small twin.

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.