First-trimester screening for early and late small-for-gestational-age neonates using maternal serum biochemistry, blood pressure and uterine artery Doppler.

OBJECTIVE: To assess the effectiveness of first-trimester screening for early and late small-for-gestational-age (SGA) neonates using maternal serum biochemistry, blood pressure and uterine artery Doppler. METHODS: This was a prospective study of 4970 women with a singleton pregnancy who underwent routine first-trimester screening between 2009 and 2011. A logistic regression-based predictive model for SGA, defined as birth weight < 10(th) percentile, divided into early- or late-onset based on gestational age at delivery before or after 34 weeks' gestation, was constructed. The model included maternal baseline characteristics: serum levels of pregnancy-associated plasma protein-A and free ß-human chorionic gonadotropin at 8-12 weeks and blood pressure and uterine artery Doppler at 11 + 0 to 13 + 6 weeks. RESULTS: The prevalence of early and late SGA was 0.6% and 7.9%, respectively. Association with pre-eclampsia was 67% and 8%, respectively. At a false-positive rate of 15%, the detection rate for early SGA was 73%; however it differed substantially for cases with and without pre-eclampsia (90% vs 40%). For late SGA, at false-positive rates of 15 and 50%, detection rates were 32% and 70%, respectively, and did not substantially differ between cases with and without pre-eclampsia. CONCLUSIONS: First-trimester screening predicts early SGA mainly because of its strong association with pre-eclampsia. Although prediction of late SGA was poorer, at a high false-positive rate it might be considered as part of a first-trimester strategy to select women requiring ultrasound assessment in the third trimester.

Angiogenic factors vs Doppler surveillance in the prediction of adverse outcome among late-pregnancy small-for- gestational-age fetuses.

OBJECTIVES: To compare the value of Doppler surveillance with maternal blood angiogenic factors at diagnosis for the prediction of adverse outcome in late-pregnancy small-for-gestational-age (SGA) fetuses. METHODS: In a cohort of 198 SGA fetuses we evaluated the association of Doppler indices (mean uterine artery pulsatility index (UtA-PI) and cerebroplacental ratio (CPR)) and angiogenic factors (maternal serum levels of soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF)) with the development of pre-eclampsia and adverse perinatal outcome (operative delivery for non-reassuring fetal status or neonatal metabolic acidosis). RESULTS: In SGA fetuses subsequently developing pre-eclampsia, mean UtA-PI (P < 0.001), sFlt-1 MoM (P < 0.001) and sFlt-1/PlGF MoM ratio (P < 0.001) were higher, while PlGF MoM was lower (P = 0.004). In SGA fetuses with adverse perinatal outcome, CPR (P < 0.002) and PlGF MoM (P < 0.001) were lower, and sFlt-1/PlGF MoM ratio was higher (P = 0.001). For predicting pre-eclampsia, the areas under the receiver-operating characteristics (ROC) curves for mean UtA-PI, sFlt-1 MoM and the combination of both were 0.852, 0.839 and 0.860, respectively. For adverse perinatal outcome, the areas under the ROC curves for CPR, PlGF MoM and the combination of both were 0.652, 0.656 and 0.684, respectively. The combination of Doppler indices and angiogenic factors did not significantly improve prediction of either pre-eclampsia (P = 0.851) or adverse outcome (P = 0.579). CONCLUSIONS: In SGA fetuses, angiogenic factors at diagnosis and follow-up with Doppler ultrasound both predict adverse outcome with a similar performance.

Cribado combinado para la deteccion del sindrome de Down en el primertrimestre de gestacion / Combined screening in the detection of Down syndrome in the first trimester

El cribado del sindrome de Down, en el primer trimestrede gestaci¨®n, incorporando dos parsmetros bioquimicos¡ªproteina plasmstica asociada al embarazo (PAPP-A) y fracciona libre de la hormona gonadotrofina cori¨®nica (f¦ÂhCG)¡ª,y un parametro ecografico ¡ªtranslucencia nucal (TN)¡ª, permiteuna mayor tasa de deteccion (96,55 % en esta serie),asumiendo una tasa de falsos positivos del 5 %. Estos resultadosmejoran de forma significativa los resultados obtenidoscon el cribado ya establecido de segundo trimestre.La incorporacion de los parsmetros bioquimicos se traduceprincipalmente en una disminuci¨®n de los falsos positivos,con la consecuente disminuci¨®n de pruebas invasivas a realizar.La tasa de detecci¨®n en este estudio es algo superior alas mostradas en otras series, hecho atribuible a la edad delas gestantes incluidas en el mismo.Debido al menor porcentaje de falsos positivos, a la mayortasa de deteccion y a la precocidad diagnostica, esta modalidadde cribado es, hoy por hoy, el metodo de eleccion pararealizar un cribado poblacional (AU)

First-trimester screening for Down¡¯s syndrome, combiningtwo biochemical markers ¨CPregnancy associatedplasma protein-A (PAPP-A) and free ¦Â human chorionicgonadotropin (f¦ÂhCG)-, and an ultrasound marker -nuchaltranslucency (NT)¨C, allows a higher detection rate(96.55% in our series) assuming a false positive rate of 5%. These results increase significantly those obtainedwith the second trimester screening.The incorporation of biochemical markers impliesmainly a reduction in the false positive rate, and consequentlya reduction of invasive methods to perform.Detection rate in this study is higher to detection ratepublished in other series. This fact can be due to the ageof pregnant women included in the present paper.The lower false positive rate, the higher detectionrate an the early diagnosis make this screening, actually,a good method to apply to general population.. (AU)

Combining fetal nuchal fold thickness with second-trimester biochemistry to screen for trisomy 21.

OBJECTIVE: To assess second-trimester screening for trisomy 21 by combining ultrasound nuchal fold (NF) measurement with maternal serum biochemistry. METHODS: NF, maternal serum alpha-fetoprotein (AFP) and free beta-human chorionic gonadotropin (beta-hCG) were determined concurrently at 14-19 weeks' gestation in a study population comprising 1813 women with singleton pregnancies, including 1257 unselected women undergoing serum screening for trisomy 21 (1999-2002), and 556 high-risk pregnancies prior to amniocentesis (2003-2005), 402 of whom had positive serum screening tests. The results were expressed in multiples of the gestation-specific normal median (MoMs). RESULTS: There were 1799 unaffected singleton pregnancies, and their NF values approximately fitted a log Gaussian distribution over a wide range. There was a weak but statistically significant correlation between log NF and log AFP (r = - 0.069, P < 0.005) and the correlation coefficient between log NF and log free beta-hCG was even smaller and not statistically significant (r = 0.038, P = 0.11). Among the seven trisomy 21 pregnancies, the median NF level was 1.53 MoM (geometric mean 1.75 MoM), a highly statistically significant increase compared with unaffected pregnancies (P < 0.0001, one-tail Wilcoxon Rank Sum Test). In pregnancies referred because of positive serum screening tests (391 unaffected, seven cases of trisomy 21, one of monosomy X and three other chromosomal anomalies) the use of NF to modify the serum screening risk would have reduced the invasive procedures in unaffected pregnancies by 46% without affecting the detection rate of trisomy 21 or other anomalies. Statistical modeling predicted that adding NF to AFP and free beta-hCG would increase detection more than would adding unconjugated estriol as well as inhibin-A, an analyte that is difficult to measure with precision. CONCLUSIONS: The addition of NF measurement to second-trimester biochemical markers improves screening performance, and could overcome drawbacks in the implementation of inhibin-A assay in clinical practice.

Cribado de trisomía 21 en el primer trimestre mediante test combinado de bioquímica y ecografía. Estudio prospective de intervención / First trimester screening for trisomy 21 with the use of the biochemistry-ultrasound combined test. A prospective intervention trial

Objetivo: Evaluar la efectividad del Test Combinado (bioquímica y ecografía en el primer trimestre) para la detección prenatal del síndrome de Down en la población general. Material y métodos: Se determinaron los marcadores bioquímicos de primer trimestre (proteína plasmática A asociada al embarazo y fracción libre de la gonadotropina coriónica) en suero materno a las 7-12 semanas. La translucencia nucal fetal y la edad gestacional se determinaron mediante ecografía a las 10-14 semanas. Se estimó el riesgo combinado el mismo día de la ecografía y se ofreció el diagnóstico citogenético mediante biopsia de corion si el riesgo era de 1:250 o superior. Resultados: La edad gestacional media en la determinación bioquímica fue de 9,5 semanas y de 12,1 para la ecografía. En las 4.447 gestaciones estudiadas con seguimiento completo, los índices de detección fueron del 91% (10/11) para la trisomía 21 y del 83% (5/6) para la trisomía 18 o 13, con una tasa de falsos positivos del 3,8% (167/4.423). Conclusión: El Test Combinado, al determinar los valores de marcadores bioquímicos y de translucencia nucal en intervalos gestacionales óptimos durante el primer trimestre, mostró una tasa de detección del 91% para la trisomía 21 con una reducción en la tasa de falsos positivos al 3,8%

Objetive: To assess the efectiveness of the Combined Test (first-trimester biochemistry and ultrasound) in the prenatal detection of Down syndrome in the general pregnant population. Material and methods: First-trimester biochemical markers (pregnancy associated plasma protein-A and free -hCG) were determined in maternal serum at 7-12 weeks. Nuchal translucency and the gestational age were assessed in a 10-14 weeks scan. The estimated combined risk was delivered the same day of the scan, and when it was 1:250 or above, cytogentic diagnosis was offered by means of chorion villus sampling. Results: The mean gestational age at biochemistry was 9.5 weeks and 12.1 for ultrasound. In the 4,447 studied pregnancies with a complete follow-up, detection rate for trisomy 21 was 91% (10/11), 83% (5/6) for trisomies 18-13, with a 3.8% (167/4423) false-positive rate. Conclusion: The Combined Test, with the assessment of biochemical markers and nuchal translucency in their optimal gestational periods during the first trimester, showed a 91% detection rate for trisomy 21 with a reduced false-positive rate of 3.8%

Cribado bioquímico y ecográfico de aneuploidía fetal en el segundo trimestre de la gestación / Biochemical and ultrasonographic screening for fetal aneuploidy in the second trimester of pregnancy

Objetivo: Estudio de la efectividad del cribado bioquímico y ecográfico en el segundo trimestre de la gestación para la detección prenatal de trisomía 21 en población de bajo riesgo de aneuploidía. Método: Estudio prospectivo de intervención de 8.894 gestaciones únicas de bajo riesgo de aneuploidía. Se realizó ecografía y extracción simultánea de sangre materna para determinación de alfafetoproteína (AFP) y fracción Beta de la gonadotropina coriónica (Beta-hCG) entre las 14 y 18 semanas. Se consideró como criterio de riesgo para ofrecer amniocentesis una estimación de riesgo superior a 1/270 combinando la edad materna y los valores de marcadores bioquímicos, valores séricos de AFP <= 0,4 múltiplos de la mediana (MoM), de Beta-hCG <= 0,2 MoM (riesgo de trisomía 18), o pliegue nucal superior al percentil 95 para la edad gestacional. Resultados: Las tasas de detección para la trisomía 21 fueron las siguientes: 65 por ciento para la bioquímica y edad materna (con un 11 por ciento de falsos positivos) y 45 por ciento para el pliegue nucal (con 5,3 por ciento de falsos positivos). Los resultados obtenidos con la aplicación de los criterios de riesgo proporcionados indistintamente por cualquiera de ambos parámetros, bioquímica o pliegue nucal, mostraron una tasa de detección del 75 por ciento con una tasa del 14,9 por ciento de falsos positivos. Conclusión: La aplicación simultánea e independiente de los marcadores bioquímicos (AFP y Beta-hCG) y del pliegue nucal para la estimación del riesgo de trisomía 21 en el segundo trimestre permitió detectar el 75 por ciento de fetos afectados, con una tasa de falsos positivos del 14,9 por ciento (AU)

Comparison of a high-carbohydrate and a high-monounsaturated fat, olive oil-rich diet on the susceptibility of LDL to oxidative modification in subjects with Type 2 diabetes mellitus.

AIMS: To compare the effects of a high-carbohydrate (CHO) diet and a high-monounsaturated fatty acid (MUFA) diet on LDL oxidative resistance in free-living individuals with Type 2 diabetes mellitus. METHODS: Twenty-two men and women out-patients with Type 2 diabetes, with mean age 61 years and in fair metabolic control (HbA1c<8.0%), were enrolled at a university hospital lipid clinic in a randomized, crossover feeding trial comparing two isocaloric diets for 6 weeks each: CHO (fat, 28% energy) and MUFA (fat, 40% energy) based on virgin olive oil. Outcome measurements were changes in LDL susceptibility to oxidation, body weight, glycaemic control, and lipoprotein profiles. RESULTS: Planned and observed diets were well matched. Participants preferred the MUFA diet over the CHO diet. The lag time of conjugated diene formation during Cu2+-induced LDL oxidation was similar after the CHO and MUFA diets (36.4 +/- 12.2 min and 36.0 +/- 13.7 min, respectively). Body weight, glycaemic control, total triglycerides, and total, LDL- and HDL-cholesterol levels also were similar after the two diets. Compared with the CHO diet, the MUFA diet lowered VLDL-cholesterol by 35% (P=0.023) and VLDL triglyceride by 16% (P=0.016). CONCLUSIONS: Natural food-based high-CHO and high-MUFA diets have similar effects on LDL oxidative resistance and metabolic control in subjects with Type 2 diabetes. A MUFA diet is a good alternative to high-CHO diets for nutrition therapy of diabetes because it also has a beneficial effect on the lipid profile and superior patient acceptance.

Effects of estradiol, cyproterone acetate, tibolone and raloxifene on uterus and aorta atherosclerosis in oophorectomized cholesterol-fed rabbits.

BACKGROUND: Different hormonal replacement regimens are used for treating climacteric complaints; however, not all of them have the same clinical profile. Cardiovascular disease (CVD) is a major health problem and tibolone, raloxifene, estradiol (alone or with cyproterone acetate) have been added to cholesterol-fed rabbits to study atherosclerosis. METHODS: A total of 48 cholesterol-fed New Zealand white rabbits were studied for 4 months. Forty rabbits underwent bilateral ovariectomy and the other eight were sham operated (group S). The ovariectomized rabbits were allocated to five groups of eight animals each receiving tibolone (Group T, 6 mg/day), raloxifene (R, 35 mg/day), estradiol valerate (E, 3 mg/day), estradiol valerate plus cyproterone acetate (EC, 3+0.5 mg/day, respectively), and no treatment for the control group (C). The sham group received no treatment too. RESULTS: After 4 months the percentage of the extent of atherosclerosis in the aorta was 30.4% in C group, 24.5% in S group, 10.2% in T group, 30.3% in R group, 17.9% in E group and 28.1% in EC group (P<0.05 T vs. C, R, EC). The aortic cholesterol content compared with aortic weight was 8.55 microg/mg in C group, 11.97 microg/mg in S group, 1.86 microg/mg in T group, 3.82 microg/mg in R group, 2.86 microg/mg in E group and 5.24 microg/mg in EC group (P<0.05 T vs. EC, C, S; R vs. C, S; E vs. C, S). Uterine weights in grams were: 1.89 (C group), 2.24 (S), 7.38 (T), 1.94 (R), 9.92 (E), and 5.94 (EC); P<0.05 (C, S, R, vs. T, E, EC; T vs. E; EC vs. T, E). CONCLUSION: Our study showed a decrease in the extent of aortic atherosclerosis in oophorectomized cholesterol-fed rabbits treated with tibolone or estradiol, and a decrease in aortic cholesterol content in rabbits treated with tibolone, raloxifene and estradiol. However, rabbits treated with tibolone showed an increased uterine weight, which is contrary to that observed in humans.