Interrater agreement for sonographic stomach position classification in fetal diaphragmatic hernia across the North American Fetal Therapy Network.

OBJECTIVE: To evaluate inter-rater agreement for sonographic classification of stomach position (as a surrogate for liver herniation) in fetal left congenital diaphragmatic hernia (LCDH) among: (i) fetal medicine specialists from the North American Fetal Therapy Network (NAFTNet) centers within and without the fetal endoscopic tracheal occlusion (FETO) consortium and in comparison to an expert external reviewer (ER1); and (iii) among two expert ERs (ER1 and ER2). METHODS: Forty-eight physicians from 26 NAFTNet centers and 2 ERs were asked to assess 13 sonographic clips of isolated LCDH and classify stomach position as "intra-abdominal," "anterior left chest," "mid to posterior left chest," or "retro-cardiac" based on the classification published by Basta et al.8 Interrater agreement was assessed by determining proportion of stomach position ratings concordant amongst NAFTNet participants and ER1. Agreement for stomach position between ERs was calculated using kappa statistics. RESULTS: Agreement for stomach position was 69% (39%-85%; n = 19) and 54% (23%-92%; n = 29) among FETO and non-FETO NAFTNet participants, respectively, when compared to ER1. Most disagreement in stomach position was related to a discrepancy of one position. ERs were in agreement for stomach position in 5 of 13 cases (38.5%) and inter-rater agreement was highest for "anterior" stomach position. CONCLUSION: Interrater agreement for stomach position assessment in CDH was poor across NAFTNet and indeed amongst expert reviewers.

Outcomes of laparoscopy-assisted fetoscopic laser photocoagulation for twin-twin transfusion syndrome: An established alternative for inaccessible anterior placenta.

OBJECTIVE: To evaluate laparoscopy-assisted fetoscopic laser photocoagulation (FLPC) of placental anastomoses in the treatment of twin-to-twin-transfusion syndrome (TTTS). STUDY DESIGN: We performed a retrospective cohort study analyzing pregnancies complicated by TTTS who underwent FLPC in a single university-affiliated tertiary medical-center. Outcomes were compared between patients who received laparoscopy-assisted FLPC (study group) and patients who underwent the conventional FLPC technique (control group). Baseline characteristics, sonographic findings, procedure details, and neonatal outcomes were compared between groups. RESULTS: The cohort included 278 women with 31 in the study group and 247 in the control group. Sonographic parameters, including fetal biometry and TTTS stage, were comparable between study groups. Gestational age at delivery did not differ between the groups (29.22 ± 4.55 weeks in the study group vs. 30.62 ± 4.3 weeks in the control group, p = 0.09). There were no differences in neonatal survival rates at birth and at 30 days between both groups. A subanalysis comparing the laparoscopy-assisted group to only those patients with anterior placenta in the control group, showed a lower rate of incomplete Solomonization in the laparoscopy-assisted study group (3.4% vs. 33%, p = 0.01). CONCLUSION: Laparoscopy-assisted FLPC is a reasonable and safe option that may be offered in cases of FLPC where an anterior placenta restricts adequate surgical access.

Testing for Zika virus infection in pregnancy: key concepts to deal with an emerging epidemic.

Zika virus is an emerging mosquito-borne (Aedes genus) arbovirus of the Flaviviridae family. Following epidemics in Micronesia and French Polynesia during the past decade, more recent Zika virus infection outbreaks were first reported in South America as early as May 2013 and spread to now 50 countries throughout the Americas. Although no other flavivirus has previously been known to cause major fetal malformations following perinatal infection, reports of a causal link between Zika virus and microcephaly, brain and ocular malformations, and fetal loss emerged from hard-hit regions of Brazil by October 2015. Among the minority of infected women with symptoms, clinical manifestations of Zika virus infection may include fever, headache, arthralgia, myalgia, and maculopapular rash; however, only 1 of every 4-5 people who are infected have any symptoms. Thus, clinical symptom reporting is an ineffective screening tool for the relative risk assessment of Zika virus infection in the majority of patients. As previously occurred with other largely asymptomatic viral infections posing perinatal transmission risk (such as HIV or cytomegalovirus), we must develop and implement rapid, sensitive, and specific screening and diagnostic testing for both viral detection and estimation of timing of exposure. Unfortunately, despite an unprecedented surge in attempts to rapidly advance perinatal clinical testing for a previously obscure arbovirus, there are several ongoing hindrances to molecular- and sonographic-based screening and diagnosis of congenital Zika virus infection. These include the following: (1) difficulty in estimating the timing of exposure for women living in endemic areas and thus limited interpretability of immunoglobulin M serologies; (2) cross-reaction of immunoglobulin serologies with other endemic flaviruses, such as dengue; (3) persistent viremia and viruria in pregnancy weeks to months after primary exposure; and (4) fetal brain malformations and anomalies preceding the sonographic detection of microcephaly. In this commentary, we discuss screening and diagnostic considerations that are grounded not only in the realities of current obstetrical practice in a largely global population but also in basic immunology and virology. We review recent epidemiological data pertaining to the risk of congenital Zika virus malformations based on trimester of exposure and consider side by side with emerging data demonstrating replication of Zika virus in placental and fetal tissue throughout gestation. We discuss limitations to ultrasound based strategies that rely largely or solely on the detection of microcephaly and provide alternative neurosonographic approaches for the detection of malformations that may precede or occur independent of a small head circumference. This expert review provides information that is of value for the following: (1) obstetrician, maternal-fetal medicine specialist, midwife, patient, and family in cases of suspected Zika virus infection; (2) review of the methodology for laboratory testing to explore the presence of the virus and the immune response; (3) ultrasound-based assessment of the fetus suspected to be exposed to Zika virus with particular emphasis on the central nervous system; and (4) identification of areas ready for development.

Severity of Fetal Brain Abnormalities in Congenital Heart Disease in Relation to the Main Expected Pattern of in utero Brain Blood Supply.

OBJECTIVES: We evaluated the hypothesis that in fetuses with congenital heart disease (CHD) there is a correlation between the expected pattern of in utero brain blood supply and the severity of neurodevelopmental impairment. METHODS: A total of 58 fetuses with CHD and 58 controls underwent a Doppler ultrasound and fetal MRI at 36-38 weeks. Fetuses with CHD were divided into two functional classes: class A with an expected severe reduction in oxygenated brain blood supply (left outflow tract obstruction and transposition of great vessels) and class B with theoretically near-normal or mildly impaired oxygenated brain blood supply (other CHD). Head biometry and cerebroplacental Doppler were assessed by ultrasound, and brain volumetry, cortical development and metabolism by MRI. RESULTS: Both class A and B CHD fetuses had significant differences in head biometry, brain perfusion, cortical development and brain metabolism compared with controls. However, there was a significant linear tendency for head biometry, cerebral Doppler, volumes, cortical sulcation and metabolic ratios across the three clinical groups, with signs of more severe brain alterations in type A CHD fetuses. CONCLUSIONS: All fetuses with CHD showed significant brain developmental changes, but differences were more pronounced in CHD associated with an expected severe reduction in oxygenated blood supply to the brain.

Evaluation of an optimal gestational age cut-off for the definition of early- and late-onset fetal growth restriction.

OBJECTIVE: The terms early- and late-onset fetal growth restriction (FGR) are commonly used to distinguish two phenotypes characterized by differences in onset, fetoplacental Doppler, association with preeclampsia (PE) and severity. We evaluated the optimal gestational age (GA) cut-off maximizing differences among these two forms. PATIENTS AND METHODS: A cohort of 656 consecutive singleton pregnancies with FGR was created. We used the decision tree analysis to evaluate the GA cut-off that best discriminated perinatal mortality, association with PE and adverse perinatal outcome (fetal demise, early neonatal death, neonatal acidosis at birth, and 5-min Apgar score <7). RESULTS: We identified 32 weeks at diagnosis as the optimal cut-off, resulting in two groups with 7.1 and 0%, p < 0.001 perinatal mortality, 35.1 and 12.1%, p < 0.001 association with PE, and 13.4 and 4.6%, p < 0.001 composite adverse perinatal outcome. Abnormal versus normal umbilical artery (UA) Doppler classified two groups with 10.6 and 0.2%, p < 0.001 perinatal mortality, 50.0 and 11.8%, p < 0.001 association with PE, and 18.2 and 4.2%, p < 0.001 composite adverse perinatal outcome. CONCLUSIONS: UA Doppler discriminated better the two forms of FGR with average early- and late-onset presentation, higher association with PE and poorer outcome. In the absence of UA information, a GA cut-off of 32 weeks at diagnosis maximizes differences between early- and late-onset FGR.

Gottesfeld-Hohler Memorial Foundation Zika Virus Think Tank Summary.

At a think tank bringing together experts on fetal neuroimaging, obstetric infectious diseases, and public health, we discussed trends in all of these areas for Zika virus. There is a wide variety of imaging findings in affected fetuses, influenced by timing of infection and probably host factors. The resources for diagnosis and interventions also vary by location with the hardest hit areas often having the fewest resources. We identified potential areas for both research and clinical collaboration as the Zika virus epidemic continues to evolve.

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.

Meningioangiomatosis in a second trimester fetus.

We describe to our knowledge the first case of meningioangiomatosis identified in a second trimester fetus. A 30-year-old pregnant woman was attended at our hospital for a second-trimester ultrasound screening scan. With a diagnosis of partial agenesis of the corpus callosum, the parents requested termination of the pregnancy. At autopsy, frontal serial sections of the fetal brain disclosed a short corpus callosum that lacked the posterior splenium, confirming the sonographic diagnosis. At close inspection, a slight bilateral hardening of both medial aspects of the frontal lobes and anterior genu of the corpus callosum was found associated with meningeal adhesion between both frontal lobes. Microscopically, cerebral cortex and corpus callosum were permeated by intersecting bundles of spindle cells with eosinophilic cytoplasm and bland, round nuclei, with a fibroblast or meningothelial-like appearance surrounding abundant blood vessels, consistent with the diagnosis of meningioangiomatosis. According to this finding, meningioangiomatosis must be included in the differential diagnosis of meningocortical fetal lesions.

Reducing blood loss at myomectomy with use of a gelatin-thrombin matrix hemostatic sealant.

OBJECTIVE: To evaluate the hemostatic efficacy and handling of gelatin-thrombin matrix in abdominal myomectomy. DESIGN: Prospective and randomized trial. SETTING: University teaching hospital. PATIENT(S): Women (n = 50) with uterine fibroids with a uterine size equivalent to > or =16 weeks gestation. INTERVENTION(S): Gelatin-thrombin matrix (FloSeal Matrix; Baxter Healthcare Corp., Fremont, CA) was delivered to the site of the uterine bleeding during myomectomy. MAIN OUTCOME MEASURE(S): Patient age, parity, number of myomas, operative time, blood loss, transfusion, intraoperative and postoperative complications, and length of hospitalization were evaluated. RESULT(S): The average blood loss during surgery was 80 +/- 25.5 mL for the FloSeal group and 625 +/- 120.5 mL for the control group. Intraoperative blood transfusion was necessary in five patients from the control group. Postoperative blood loss was 25 +/- 5 mL for the FloSeal group and 250 +/- 75 mL for the control group. Length of the postoperative hospital stay was 2.5 +/- 1.2 days for FloSeal group and 4.5 +/- 1.3 for the control group. No major immediate or delayed complications were observed in either group. CONCLUSION(S): Reductions in hemorrhage in FloSeal-treated women undergoing a myomectomy are encouraging, and provide evidence for the ability of gelatin-thrombin matrix to reduce blood loss when applied immediately and directly to bleeding uterine tissue.

Cotyledonoid dissecting leiomyoma of the uterus.

We describe a cotyledonoid dissecting leiomyoma in a 33-year-old nulliparous woman treated by laparoscopy.