Congenital metastatic neuroblastoma with placental involvement as a rare cause of non-immune fetal hydrops.

Non-immune hydrops fetalis represents the end-stage status of a variety of diseases, including metastatic tumors. We report a case of non-immune hydrops fetalis associated with multiple disseminated echogenic nodular lesions detected by ultrasound and confirmed by magnetic resonance. Cordocentesis demonstrated anemia and thrombopenia. Differential diagnosis included histiocytosis X, acute leukemia or metastatic disease. A stillbirth was diagnosed at week 25 + 6. The autopsy revealed hydrops fetalis, a right adrenal gland mass, multiple disseminated nodules histologically composed of small round blue cells positive for synaptophysin, and placental involvement, concordant findings with congenital undifferentiated neuroblastoma Stage M. No chromosomal abnormalities were associated, nor amplification abnormalities in MYCN and ALK genes. Metastatic neuroblastoma should be considered in the differential diagnosis of non-immune hydrops fetalis associated with multiple nodular lesions.

Prenatal prediction of very late onset small-for-gestational age newborns in low-risk pregnancies.

OBJECTIVE: To find a multivariate model for predicting small-for-gestational age newborns at 36 weeks' gestation by using clinical, biochemical and ultrasound measurements. MATERIALS AND METHODS: We evaluated 564 low-risk pregnant women and recorded maternal age, maternal body mass index, maternal mean blood pressure, soluble fms-like tyrosine kinase-1 (multiples of the median), placental growth factor (multiples of the median), soluble fms-like tyrosine kinase-1/placental growth factor ratio, estimated fetal weight centile and mean uterine artery pulsatility index at 36 weeks. Binary logistic regression was used. Statistical significance was set at 95% level (p < 0.05). RESULTS: We found three multivariate models showing relatively small differences in predictive capability. Model 1 only included estimated fetal weight centiles (area under the curve [AUC] 0.86; R2 = 0.42; p < 0.0001), Model 2 estimated fetal weight centiles and placental growth factor (multiples of the median) (AUC 0.87; R2 = 0.44; p < 0.0001) and Model 3 estimated fetal weight centiles, placental growth factor (multiples of the median) and mean uterine artery pulsatility index (AUC 0.88; R2 = 0.45; p < 0.0001). CONCLUSION: Small-for-gestational age at delivery may be predicted by using a multivariate formula. The inclusion of parameters other than estimated fetal weight centile at 36 weeks' gestation modestly improves the predictive capability of the model. Clinical decisions should consider whether or not these slight differences deserve a change in current strategies.

Third trimester ultrasound estimated fetal weight for increasing prenatal prediction of small-for-gestational age newborns in low-risk pregnant women.

AIM: The early detection of small-for-gestational age (SGA) fetuses and newborns is pivotal in the prevention of perinatal mortality. OBJECTIVES: To compare the predictive capability of performing ultrasound-based estimated fetal weight (EFW) at 32 versus 36 weeks' gestation on the detection rate of SGA fetuses and SGA newborns at delivery, and to find a better cutoff level to consider a fetus at risk of being born small. MATERIAL AND METHODS: Nine hundred fifteen low-risk pregnant women were assessed at both 32 and 36 weeks' gestation. EFW centile was calculated in both occasions. The rate of SGA fetuses was compared. SGA fetuses were considered when both abdominal circumference (AC) and EFW were below the 10th centile from a total of 488 delivered at our Hospital. Paired comparisons between ultrasound at 32 and 36 weeks' gestation were done to predict SGA at delivery. Percentages of SGA fetuses were compared by chi-squared test. ANOVA test was used for comparing centiles among groups. Receiver operating characteristic (ROC) curve was used to find the best cutoff ultrasound centile to predict SGA at delivery. Statistical significance was previously set at 95% level (p < .05). RESULTS: Ultrasound-based EFW at 32 weeks showed 23 cases of SGA (2.5%) while at 36 weeks this rate increased up to 4% (37/915) (p < .000001). When comparing both outcomes, 2.8% of those catalogued as adequate-for-gestational age (AGA) at 32 weeks were cases of SGA at 36 weeks. In addition, 47.8% of those diagnosed as SGA were not confirmed at 36 weeks. Only 12.3% of SGA neonates were identified at 32 weeks' gestation ultrasound, while using the 36 weeks' gestation approach this rate increased up to 30.9%. So, only a low proportion of SGA neonates were SGA fetuses at any of these two gestational ages. However, the area under the curve (AUC) at 36 weeks was as high as 0.86. Being a matter of cutoff rather than a matter of choosing the correct variable, ROC analysis showed that the best cutoff for prediction having the best sensitivity (0.80) with the best specificity (0.77) was 28th centile of EFW. This represents 24.9% of the studied women (228/915). CONCLUSIONS: In general, ultrasound at 36 weeks has better performance detecting SGA fetuses than ultrasound at 32 weeks and we suggest to definitively change from 32 to 36 weeks in order to increase the detection rate of SGA fetuses. Moreover, in order to detect those fetuses who will grow below the lower level of the normal range in the last month of pregnancy, we suggest that those with EFW below the 28th centile at 36 weeks should be rescanned later in pregnancy to identify prenatally as many cases as we can of SGA newborns.

Spontaneous twin anemia-polycythemia sequence from two donors to one recipient in a monochorionic triamniotic pregnancy: Case report and review of the literature.

Monochorionic triamniotic (MCTA) pregnancies present a high number of complications, mainly due to the presence of unbalanced vascular anastomoses, such as twin anemia-polycythemia sequence (TAPS). Previous reported cases related to TAPS are in twin pregnancies or only affect the monochorionic component of dichorionic triamniotic (DCTA) pregnancies. We report an exceptional case, the only one reported as far as we know, of a MCTA pregnancy that developed a TAPS in which the three triplets are implicated, from two donors to one recipient. The pregnancy had been previously sonographically diagnosed as DCTA pregnancy and this could not explain the clinical results. The pathological study of the placenta showed the presence of three monochorionic dividing membranes, a congested area in the recipient parenchyma and two non-congested areas in the donor's parenchyma that confirmed the clinical findings. Pathological study of multiple placentas should always be done because it provides understanding of pregnancy complications.

Prenatal ultrasound findings in Koolen-de Vries foetuses: Central nervous system anomalies are frequent markers of this syndrome.

OBJECTIVE: Prenatal diagnoses of microdeletion syndromes without ultrasound findings in the first and second trimester are always difficult. The objective of this study is to report the prenatal ultrasound findings in four foetuses diagnosed with 17q21.31 microdeletions (Koolen-de Vries syndrome) using chromosomal microarrays (CMA). PATIENTS AND METHODS: We present four foetuses with 17q21.31 microdeletion. All showed CNS anomalies in the third trimester, three had ventriculomegaly, and one hypogenesis of corpus callosum at 31 weeks of pregnancy. RESULTS: Array-SNPs and CGH-array were performed on uncultured amniocytes and peripheral blood revealing a 17q21.31 microdeletion. CONCLUSIONS: Prenatal CNS anomalies (mainly ventriculomegaly) at third trimester, in spite of isolate, should be considered a prenatal ultrasound marker of this syndrome. This kind of malformations raise the possibility of an underlying genetic conditions including 17q21.31 microdeletion; thus, CMA should be taken into consideration when offering prenatal genetic counselling.

Treatment of infantile fibrosarcoma associated to an abdominal aortic aneurysm with larotrectinib: a case report.

Infantile fibrosarcoma (IFS) is a rare pediatric tumor which often presents the ETV6-NTRK3 gene fusion. NTRK3 encodes the neurotrophin-3 growth factor receptor tyrosine kinase, a druggable therapeutic target. Selective tropomyosin receptor kinase (TRK) inhibitors, such as larotrectinib, have shown efficacy and safety in the treatment of IFS. We report a case of an abdominal IFS diagnosed in a newborn associated with an aortic aneurysm that was successfully treated with larotrectinib without relevant adverse effects.

Characteristics of Zika virus infection among international travelers: A prospective study from a Spanish referral unit.

BACKGROUND: From the first Zika virus (ZIKV) description, it has progressively widespread worldwide. We analyzed demographic, clinical, microbiologic and travel-related characteristic from returned patients from a ZIKV endemic country in a referral Tropical Medicine Unit. METHOD: A prospective cohort study performed in a Spanish referral center with the aim of determining the significant factors associated with confirmed Zika virus (ZIKV) infection. RESULTS: 817 patients, (56% women, median age 36 [IQR, Interquartile Range: 32-42]) were enrolled. Most had returned from Latin America (n = 486; 59.4%), travelled for tourism (n = 404; 49.4%) and stayed a median of 18 days (IQR: 10-30). 602 (73.6%) presented symptoms, but only 25 (4%) were finally diagnosed with confirmed ZIKV infection (including two pregnant women, without adverse fetal outcomes), 88% (n:22) presented with fever and 92% (n:23) with rash. 56% (n:14) arthralgia and/or myalgia and 28% (n:7) conjunctivitis. The presence of conjunctivitis, fever and rash were associated with an 8.9 (95% CI: 2.2-34.9), 6.4 (95% CI: 1.2-33.3) and 72.3 (95% CI: 9.2-563.5) times greater probability of confirmed ZIKV infection, respectively. CONCLUSION: Travel characteristics and clinical presentation may help clinicians to optimize requests for microbiological testing. Diagnosis of arboviriasis in travellers arriving form endemic areas remains a challenge for clinicians, but must be detected for the possible transmission outside endemic areas, where the vector is present.

Evaluation of Fetal Lung Maturity by Quantitative Analysis (quantusFLM) in Women with Gestational Diabetes Mellitus.

OBJECTIVES: The aim of the present study was to evaluate fetal lung maturity using the noninvasive method of quantitative ultrasound analysis of fetal lung texture (quantusFLM) in women with gestational diabetes mellitus (GDM). METHODS: A total of 96 women at 36-38 weeks of gestation were enrolled. They were classified as follows: 33 GDM cases treated with diet, 30 GDM cases treated with diet plus insulin, and 33 normoglycemic women (control group). A quantitative analysis of lung texture was performed. RESULTS: There were significant differences in the lung maturity results among groups (p = 0.004). These differences were established between the insulin-treated group of patients and both the control (p = 0.006) and diet-only (p = 0.003) groups. While none of the women in the control group or in the diet group had a high risk of immaturity, 16.7% of those treated with insulin (5/30) did (p = 0.003). There was no statistically significant correlation between HbA1c and the result of the test. CONCLUSIONS: Quantitative ultrasound study of fetal lung texture suggests that a significant percentage of pregnant women with GDM treated with insulin had fetal lung immaturity in the late preterm to early term.

The effect of a triple therapy on maternal anti-Ro/SS-A levels associated to fetal cardiac manifestations.

OBJECTIVE: To evaluate the efficacy and safety of the combination of steroids, plasmapheresis and intravenous immunoglobulins (IVIG) on maternal anti Ro/SS-A antibody levels in cases of fetal cardiac involvement. MATERIAL AND METHODS: A series of three cases of positive anti-Ro/SS-A mothers with fetuses showing mild cardiac involvement were treated with a triple therapy composed of steroids, plasmapheresis and IVIG. Maternal antibody levels were measured several times before and after the application of each cycle of therapy. The effect of the treatment on fetal cardiac manifestations was also evaluated. RESULTS: Maternal anti-Ro/SS-A levels significantly decreased after each cycle of either plasmapheresis or IVIG therapy. The most significant decrease occurred after the first cycle. The natural evolution of the disease was stopped by this therapy in two of these cases, signs of cardiac inflammation decrease and none of the newborns needed neonatal pacemaker. CONCLUSIONS: A triple therapy combining plasmapheresis, IVIG and glucocorticoids may stop the natural evolution of the fetal cardiac affectation in positive anti-Ro/SS-A antibody patients. Further studies are needed in order to validate clinical applications of this treatment approach.

Second trimester amniotic fluid adiponectin level is affected by maternal tobacco exposure, insulin, and PAPP-A level.

OBJECTIVES: Adiponectin is an adipocyte-derived plasma protein with insulin-sensitizing and antiatherosclerotic properties. The objectives of the present study were to determine the amniotic fluid (AF) concentration of adiponectin during the second trimester of pregnancy and to demonstrate its association with maternal and fetal variables and AF concentrations of insulin, leptin, and pregnancy-associated-plasma-protein A (PAPP-A). STUDY DESIGN: We performed a cross-sectional study of 222 pregnant women who underwent amniocentesis at 15-18 weeks for genetic reasons. No malformation or chromosomal disorder was found in the newborn after birth. AF adiponectin, leptin, PAPP-A, and insulin concentrations were measured using commercially available assays. All maternal, fetal, and biochemical variables were studied using univariate and multivariate linear regression analysis to determine their association with the AF concentration of adiponectin. RESULTS: Adiponectin concentration was negatively correlated with maternal smoking status (ß=-5.208; p<0.001) and positively correlated with levels of insulin (ß=0.621; p=0.002) and PAPP-A (ß=40.150; p<0.001). Non-significant correlations were found between adiponectin concentration and maternal age, maternal body mass index, gestational age at amniocentesis, fetal gender, and AF level of leptin. CONCLUSION: These findings suggest that the fetus and its membrane adipocytokines, in relationship with maternal and other fetal variables, play a dynamic role in the regulation of energy and oxidative stress homeostasis due to its insulin-sensitizing and antiatherosclerotic effects. The association of these molecules with maternal tobacco consumption during pregnancy could have perinatal implications.