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.

Visualización ecográfica y diagnóstico prenatal del arco aórtico derecho / Prenatal ultrasound-guided visualisation and diagnosis of right aortic arch

Presentamos un caso de diagnóstico prenatal de arco aórtico derecho (AAD) aislado y se describe el manejo diagnóstico-clínico de esta entidad. En la exploración ecográfica fetal de una gestante de 20 semanas se detectó un AAD sin otras malformaciones asociadas. Mediante un corte axial del tórax fetal a nivel del plano de tres-vasos-tráquea, se comprobó el trayecto anómalo del arco aórtico, a la derecha de la tráquea. El AAD es una entidad rara (prevalencia del 0,1%) y sus variantes pueden condicionar sintomatología compresiva y estar relacionadas con anomalías cardíacas (hasta 90%) y/o con la microdeleción 22q11 (hasta 46%). El corte ecográfico de tres-vasos-tráquea es fundamental para su diagnóstico prenatal y tras su detección está indicada una evaluación exhaustiva del corazón fetal, distinguir sus variantes y/o un estudio cromosómico-genético específico. En presencia de otras anomalías el pronóstico es pobre; los casos aislados suelen tener una evolución postnatal oligo o asintomática(AU)

We report a case of prenatally diagnosed isolated right aortic arch (RAA) and describe the procedure for its ultrasound-guided diagnosis and clinical management. The ultrasound scan of a 20-week-old fetus revealed an isolated RAA. The diagnosis was achieved using the 3 vessels and trachea view, in which the aortic arch was visualized to the right side of the trachea. RAA is a rare finding (incidence, 0.1%) and its variants may cause compressive symptoms and be associated with congenital heart defects (up to 90%) and/or 22q11 microdeletion (up to 46%). The 3 vessels and trachea view is essential for the prenatal diagnosis of RAA. Detection of this condition must be considered an indication for fetal echocardiography, to distinguish its variants, and a genetic study is also recommended. Isolated RAA is usually asymptomatic, although the outcome of RAA associated with other abnormalities is uncertain(AU)

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.

Patología valvular pulmonar del feto receptor en el síndrome de transfusión feto-fetal: impacto de la fotocoagulación mediante láser de las anastomosis vasculares / Pulmonary valve disease in recipient fetuses in twin to twin transfusion syndrome: Impact of laser therapy

Introducción. La obstrucción del tracto de salida del ventrículo derecho (OTSVD) es la anomalía cardiaca más frecuente del feto receptor en el síndrome de transfusión feto-fetal (STFF). La fotocoagulación mediante láser de las anastomosis vasculares parece influir en su evolución. El objetivo del estudio es analizar el efecto del tratamiento quirúrgico del STFF en la evolución de la OTSVD del receptor. Material y métodos. Análisis retrospectivo unicéntrico de los STFF en los que se estableció el diagnóstico de OTSVD en el gemelo receptor (abril 2008-diciembre 2011). Se realizaron exploraciones ecocardiográficas seriadas, valorando la evolución de la OTSVD tras el tratamiento intrauterino (láser u oclusión de cordón [OC]). Se recogió la supervivencia neonatal, confirmación de la valvulopatía al nacimiento y necesidad de valvuloplastia. Resultados. La incidencia de OTSVD en los receptores fue del 20,8% (16/77), siendo catalogada de estenosis pulmonar (EP) en 13 casos (16,9%) y de disminución del ratio calibre pulmonar/aorta en 3 (3,9%). Se realizó tratamiento quirúrgico intrauterino en 14 casos (13 láser y una OC del feto donante). La obstrucción se resolvió tras la técnica en 5 casos (35,7%). En los 6 casos en que la OTSVD persistió, el diagnóstico se confirmó al nacimiento, requiriendo todos ellos tratamiento corrector postnatal. La supervivencia a los 28 días de vida del gemelo receptor fue del 68,8% (11/16). Conclusiones. La incidencia de OTSVD es elevada, siendo en nuestra serie similar a la descrita por otros autores. Pese a la potencial reversibilidad tras la fotocoagulación de las anastomosis vasculares, la enfermedad de la válvula puede persistir requiriendo tratamiento postnatal la mayoría de los casos(AU)

Introduction. Right ventricular outflow tract obstruction (RVOTO) is the most common cardiac defect of the recipient fetus in twin-twin transfusion syndrome (TTTS). Fetoscopic laser photocoagulation of communicating vessels appears to influence its outcome. We aim to investigate the effect of surgical treatment of TTTS in the progression of RVOTO. Material and methods. Retrospective single center study of cases of TTTS in which RVOTO was established in the recipient twin (April 2008-December 2011). Postoperative echocardiograms from recipients who had undergone fetal surgery (laser or cord occlusion [CO]) were reviewed, and the evolution of RVOTO was analyzed. Neonatal survival, pulmonary valve abnormalities documented at birth, and the need for postnatal intervention were collected. Results. The incidence of RVOTO in recipients was 20.8% (16/77), pulmonary stenosis (PS) in 13 cases (16.9%) and decreased pulmonary/aorta ratio in 3 (3.9%). Intrauterine surgery was performed in 14 cases (13 laser photocoagulation of communicating vessels and one CO of the donor). The obstruction was resolved after surgery in 5 cases (35.7%). The diagnosis was confirmed at birth in the 6 cases where RVOTO persisted, and all of them required postnatal corrective treatment. Survival rate of the recipient twin up to 28 days was 68.8% (11/16). Conclusions. The incidence of RVOTO in our series is high, similar to that described previously. Despite the potential reversibility after photocoagulation of communicating vessels, valve disease may persist, and postnatal treatment will be required in most cases(AU)

Estudio de la función cardiaca en el síndrome de transfusión feto fetal / Assessment of fetal cardiac function in twin to twin transfusion syndrome

Introducción. En el síndrome de transfusión feto fetal (STFF) existe una disfunción cardiaca, principalmente en el feto receptor. Se ha descrito una mejora de la misma tras la fotocoagulación mediante láser de las anastomosis vasculares. Objetivos. Evaluar la función cardiaca en el STFF, su relación con los estadios de Quintero y el posible impacto del tratamiento intrauterino. Material y métodos. Se incluyeron de manera consecutiva 58 STFF (marzo 2009-marzo 2012) en los que se evaluó la función cardiaca de manera prospectiva, tanto en el feto receptor como en el donante, antes y 48-72 h tras el procedimiento (fotocoagulación mediante láser de las anastomosis vasculares u oclusión de cordón umbilical). Resultados. En el 88% (51/58) de los casos fue posible una exploración cardiovascular completa. Hasta en el 90% de los estadios i y ii el feto receptor presentó un índice de Tei en ventrículo izquierdo > 3 Z-Score. Tras la técnica, la función cardiaca derecha mejoró en el feto receptor. No se hallaron diferencias en el índice de Tei del ventrículo izquierdo. Los fetos donantes mostraron una mejora significativa en la onda de velocidad de flujo de la arteria umbilical y una tendencia a un empeoramiento de la función cardiaca derecha. Conclusiones. En el STFF, el feto receptor presenta un menor o mayor grado de disfunción cardiaca en un porcentaje elevado de casos. Esta puede presentarse en estadios iniciales de Quintero. El tratamiento intrauterino induce modificaciones en la función cardiaca. A corto plazo, los fetos receptores muestran una mejora de la función cardiaca derecha y los donantes un deterioro(AU)

Introduction. Twin to twin transfusion syndrome (TTTS) leads to cardiac dysfunction, mainly in the recipient twin. After laser ablation of placental anastomoses, an improvement has been described. Objectives. To assess cardiac function in both recipient and donor twins in TTTS, its association with Quintero stages, and the impact of intrauterine therapy. Material and methods. Prospective study based on 58 consecutive TTTS referred to a single centre (March 2008-March 2012). Assessment of cardiac function was performed on the recipient and donor fetuses before and 48-72h after the procedure (laser photocoagulation of placental anastomoses or cord occlusion). Results. A complete cardiovascular examination was possible in 88% (51/58). Up to 90% of stage i and ii recipients showed a left ventricle Tei index >3Z-Score. After intrauterine treatment of TTTS, the right heart function improved in recipient fetuses. No differences were found in left ventricle Tei index. In donor twins, there was a significant decrease in pathological blood flow velocity waveform in the umbilical artery and a trend to a worse right cardiac function. Conclusions. In TTTS, cardiac dysfunction commonly affects the recipient twin. This is already present at early stages of Quintero. Intrauterine therapy induces changes in cardiac function. Shortly after the procedure, right heart function improves in recipient twins but it worsens in the donors(AU)

Malformaciones esqueléticas: diagnóstico ecográfico y resultados perinatales / Skeletal malformations: ultrasound diagnosis and perinatal results

Introducción. la incidencia de las alteraciones del desarrollo de las estructuras osteocartilaginosas fetales es baja. Aunque su diagnóstico ecográfico es sencillo, especialmente en las osteocondrodisplasias letales, llegar a un diagnóstico etiológico es complicado. El objetivo del presente trabajo es presentar los hallazgos ecográficos y resultados perinatales de las malformaciones esqueléticas diagnosticadas en nuestro centro. Material y métodos. estudio descriptivo retrospectivo de serie de casos. Se incluyeron las malformaciones esqueléticas diagnosticadas prenatalmente en la Sección de Medicina Fetal del Hospital General Universitario Gregorio Marañón (noviembre de 2004-febrero de 2010). Los casos se clasificaron en defectos del esqueleto axial o radial, tanto focales aislados como cuadros generalizados de displasias óseas. Se analizaron la edad gestacional al diagnóstico, los defectos congénitos asociados y los resultados perinatales. Resultados. durante el período de estudio se registraron 56 casos. La edad gestacional media al diagnóstico fue de 23,7 semanas (rango 12-37; desviación estándar 7,25). Veintiséis (46,4%) se presentaron como malformación aislada; 14 (25%) asociadas a otras malformaciones, y 16 (28,6%) en el contexto de un síndrome polimalformativo. De los 29 (51,8%) casos en que se realizó estudio citogenético, en 10 (34,5%) se diagnóstico una cromosomopatía. En 40 casos (71,4%) el diagnóstico fue de anomalía focal del esqueleto radial; en 5 (8,9%), de anomalía del esqueleto axial, y en 14 (25%), de osteocondrodisplasia. Sólo en 11 casos se estableció un diagnóstico nosológico. La supervivencia en el período neonatal fue del 61,1% (33/54). Conclusiones. las malformaciones esqueléticas se asocian frecuentemente a otros defectos congénitos, de difícil diagnóstico etiológico y con una alta tasa de resultado perinatal adverso(AU)

Introduction. The incidence of disorders in the development of foetal bone and cartilage structures is low. Although ultrasound diagnosis is easy, especially in lethal skeletal dysplasias, to reach an aetiological diagnosis can be difficult. The aim of this study was to present the ultrasound findings and perinatal outcomes of skeletal malformations diagnosed in our centre. Material and methods. A retrospective descriptive study of case series. Skeletal malformations prenatally diagnosed in the Foetal Medicine Unit at the Gregorio Marañón General University Hospital (HGUGM) Madrid between November 2004 and February 2010 were included. Cases were classified as axial or radial skeletal defects, including isolated defects, as well as generalised skeletal dysplasias. Gestational age at diagnosis, presence of associated congenital defects and perinatal outcome were recorded. Results. A total of 56 cases were included during the study period. The mean gestational age at diagnosis was 23.7 weeks (range 11-36, standard deviation 7.25). Twenty-six (46.4%) occurred as an isolated malformation, 14 (25%) associated to other malformations, and 16 (28.6%) as a multiple malformation syndrome. Among the 29 (51.8%) cases in which a cytogenetic study was performed, 10 (34.5%) had a chromosomal abnormality. The diagnosis was a radial skeletal focal anomaly in 40 cases (71.4%); anomalies of the axial skeleton in 5 (8.9%); and osteochondrodysplasia in 14 (25%). A nosological diagnosis was established in only 11 cases. Neonatal survival was 61.1% (33/54). Conclusions. Skeletal malformations are often associated with other congenital defects. Aetiological diagnosis may be extremely difficult and the rate of adverse perinatal outcomes is high(AU)