Impact of aspirin on trophoblastic invasion in women with abnormal uterine artery Doppler at 11-14 weeks: a randomized controlled study.

OBJECTIVE: Defective trophoblastic invasion is a key feature in many cases of pre-eclampsia (PE). Uterine artery (UtA) Doppler is a validated non-invasive proxy for trophoblastic invasion. The aim of this study was to explore whether low-dose aspirin, administered from the first trimester, improves trophoblastic invasion, evaluated by UtA Doppler during the second and third trimesters in women defined as high risk by abnormal first-trimester UtA Doppler. METHODS: This randomized Phase-II study had a triple-blind, parallel-arm, controlled design. Singleton pregnancies with abnormal mean UtA Doppler at 11-14 weeks and absence of other major risk factors for PE received 150 mg extended-release aspirin or identical-appearing placebo tablets from study inclusion to 28 weeks. Main outcome measure was UtA pulsatility index (PI) at 28 weeks' gestation. Secondary outcomes included frequency of development of PE and growth restriction/small-for-gestational age (SGA). RESULTS: A total of 155 women completed the follow-up and were analyzed. No difference in mean UtA-PI was found between women in the aspirin and placebo groups at 28 weeks (mean UtA-PI Z-score (mean ± SD), 0.99 ± 1.48 vs 0.85 ± 1.25; P = 0.52). Seven women developed PE: four (5%) in the aspirin group and three (4%) in the placebo group. There was a trend toward lower incidence of SGA in the aspirin group (8.8% vs 17.3%; P = 0.11). CONCLUSION: In women with defective trophoblastic invasion, as reflected by abnormal UtA Doppler, low-dose aspirin started in the first trimester does not have a significant effect on UtA impedance as pregnancy progresses; however, the study was underpowered to detect potential small effects . Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Changes in uterine artery Doppler velocimetry and circulating angiogenic factors in the first half of pregnancies delivering a small-for-gestational-age neonate.

OBJECTIVE: To assess the relationship between longitudinal changes in placental Doppler indices and maternal circulating angiogenic factors in the first half of pregnancy and delivery of a small-for-gestational-age (SGA) neonate, and ascertain whether longitudinal evaluation of these variables improves the prediction achieved by second-trimester cross-sectional evaluation. METHODS: From a prospective cohort of unselected singleton pregnancies undergoing first-trimester screening for aneuploidy, 138 were included in this study. Of these, 46 were complicated by SGA (delivering after 34 weeks' gestation with a birth weight < 10th centile) and 92 were appropriate-for-gestational-age (AGA) pregnancies, which were included as controls (ratio 1:2). First-to-second trimester longitudinal changes in uterine artery (UtA) Doppler indices and maternal circulating levels of placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) were analyzed. RESULTS: Compared with the AGA group, SGA pregnancies had significantly higher UtA impedance in the first (Z-score: 0.46 vs -0.57; P < 0.001) and second (Z-score: 1.71 vs -0.75; P < 0.001) trimesters. Likewise, the sFlt-1/PlGF ratio was significantly higher in SGA than in AGA pregnancies in the first (98.0 vs 67.9; P = 0.01) and early second (22.4 vs 8.8; P < 0.001) trimesters. The predictive performance of the longitudinal changes in UtA Doppler indices for SGA was significantly lower than that of second-trimester cross-sectional values (area under receiver-operating characteristics curve (AUC), 60.8% vs 84.3%; P = 0.0035). The detection rate of SGA, at a 10% false-positive rate (FPR), was 17.7% by longitudinal changes in UtA Doppler and 56.2% by second-trimester cross-sectional UtA Doppler values. Similarly, the predictive performance of the longitudinal changes in PlGF was significantly lower than that of early second-trimester cross-sectional values (AUC, 71.4% vs 76.5%; P = 0.008). The detection rate of SGA at a 10% FPR was 40.6% when screening by longitudinal changes in PlGF and 52.1% when screening by early second-trimester cross-sectional values. CONCLUSIONS: First- and second-trimester UtA Doppler velocimetry and maternal circulating angiogenic markers have clinical utility as a cross-sectional assessment for the identification of pregnancies at high risk of delivering a SGA neonate, however, they do not improve prediction when their longitudinal changes are used. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Validation of a first-trimester screening model for pre-eclampsia in an unselected population.

OBJECTIVE: To validate the performance of a previously constructed first-trimester predictive model for pre-eclampsia (PE) in routine care of an unselected population. METHODS: A validation cohort of 4621 consecutive women attending their routine first-trimester ultrasound examination was used to test a prediction model for PE that had been developed previously in 5170 women. The prediction model included maternal factors, uterine artery Doppler, blood pressure and pregnancy-associated plasma protein-A. Model performance was evaluated using receiver-operating characteristics (ROC) curve analysis and ROC curves from both cohorts were compared unpaired. RESULTS: Among the 4203 women included in the final analysis, 169 (4.0%) developed PE, including 141 (3.4%) cases of late-onset PE and 28 (0.7%) cases of early-onset PE. For early-onset PE, the model showed an area under the ROC curve of 0.94 (95% CI, 0.88-0.99), which did not differ significantly (P = 0.37) from that obtained in the construction cohort (0.88 (95% CI, 0.78-0.99)). For late-onset PE, the final model showed an area under the ROC curve of 0.72 (95% CI, 0.66-0.77), which did not differ significantly (P = 0.49) from that obtained in the construction cohort (0.75 (95% CI, 0.67-0.82)). CONCLUSION: The prediction model for PE achieved a similar performance to that obtained in the construction cohort when tested on a subsequent cohort of women, confirming its validity as a predictive model for PE. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Vaginal progesterone as maintenance treatment after an episode of preterm labour (PROMISE) study: a multicentre, double-blind, randomised, placebo-controlled trial.

OBJECTIVE: To evaluate whether maintenance treatment with vaginal progesterone after an arrested preterm labour reduces the incidence of preterm delivery. DESIGN: Multicentre, randomised, double-blind, placebo-controlled trial. SETTING: Twelve tertiary care centres in Spain. POPULATION: A total of 265 women with singleton pregnancy, preterm labour successfully arrested with tocolytic treatment, and cervical length of <25 mm. METHODS: Randomisation was stratified by gestational age (from 24.0 to <31.0 weeks of gestation and from 31.0 to <34.0 weeks of gestation) and centre. Patients were randomly assigned, in a 1 : 1 ratio, to either daily vaginal capsules of 200 mg progesterone or placebo until delivery or 36.6 weeks of gestation, whichever occurred first. MAIN OUTCOME MEASURES: Primary outcome was delivery before 34.0 and 37.0 weeks of gestation. Secondary outcomes were discharge-to-delivery time, readmissions because of preterm labour, emergency service use, and neonatal morbidity and mortality. RESULTS: From June 2008 through June 2012, 1419 women were screened: 472 met the inclusion criteria and 265 were randomised. The final analysis included 258 women: 126 in the progesterone group and 132 in the placebo group. There were no significant differences between the progesterone and placebo groups in terms of delivery at <34 weeks of gestation [9/126 (7.1%) versus 10/132 (7.6%), P = 0.91] or <37 weeks of gestation [36/126 (28.6%) versus 29/132 (22.0%), P = 0.22]. There were no differences observed between groups when considering the two strata of gestational age at inclusion. CONCLUSIONS: A maintenance treatment of 200 mg of daily vaginal progesterone capsules in women discharged home after an episode of arrested preterm labour did not significantly reduce the rate of preterm delivery. TWEETABLE ABSTRACT: Maintenance progesterone in 258 women after arrested PTL showed no benefit.

Contingent versus routine third-trimester screening for late fetal growth restriction.

OBJECTIVE: To evaluate the use of third-trimester ultrasound screening for late fetal growth restriction (FGR) on a contingent basis, according to risk accrued in the second trimester, in an unselected population. METHODS: Maternal characteristics, fetal biometry and second-trimester uterine artery (UtA) Doppler were included in logistic regression analysis to estimate risk for late FGR (birth weight < 3(rd) percentile, or 3(rd) -10(th) percentile plus abnormal cerebroplacental ratio or UtA Doppler, with delivery ≥ 34 weeks). Based on the second-trimester risk, strategies for performing contingent third-trimester ultrasound examinations in 10%, 25% or 50% of the cohort were tested against a strategy of routine ultrasound scanning in the entire population at 32 + 0 to 33 + 6 weeks. RESULTS: Models were constructed based on 1393 patients and validated in 1303 patients, including 73 (5.2%) and 82 late FGR (6.3%) cases, respectively. At the second-trimester scan, the a-posteriori second-trimester risk (a-posteriori first-trimester risk (baseline a-priori risk and mean arterial blood pressure) combined with second-trimester abdominal circumference and UtA Doppler) yielded an area under the receiver-operating characteristics curve (AUC) of 0.81 (95% CI, 0.74-0.87) (detection rate (DR), 43.1% for a 10% false-positive rate (FPR)). The combination of a-posteriori second-trimester risk plus third-trimester estimated fetal weight (full model) yielded an AUC of 0.92 (95% CI, 0.88-0.96) (DR, 74% for a 10% FPR). Subjecting 10%, 25% or 50% of the study population to third-trimester ultrasound, based on a-posteriori second-trimester risk, gave AUCs of 0.81 (95% CI, 0.75-0.88), 0.84 (95% CI, 0.78-0.91) and 0.89 (95% CI, 0.84-0.94), respectively. Only the 50% contingent model proved statistically equivalent to performing routine third-trimester ultrasound scans (AUC, 0.92 (95% CI, 0.88-0.96), P = 0.11). CONCLUSION: A strategy of selecting 50% of the study population to undergo third-trimester ultrasound examination, based on accrued risk in the second trimester, proved equivalent to routine third-trimester ultrasound scanning in predicting late FGR.

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.

Resultados del estudio del genotipado RhD fetal en plasma materno / Results of the study of the fetal RHD genotyping in maternal plasma

Introducción. Se evalúa la eficacia en la determinacióndel RhD fetal a partir de sangre materna.Material y métodos. Estudio prospectivo y descriptivo.Se obtuvieron 90 muestras sanguíneas de gestantes RhD negativo con pareja RhD positiva que controlaron su gestación en nuestro centro entre septiembre de 2004 y enero de 2006, previa autorización y consentimiento expreso de las pacientes. Las muestras de sangre materna se enviaron al laboratorio de biología molecular para cuantificar los exones 7 y 10 del gen RHD. Posterior-mente se compararon los resultados obtenidos del genotipado RHD fetal con el fenotipo de RhDde los recién nacidos.Resultados. El genotipado informó de 69 fetos RhD positivo (76,6%) y 21 RhD negativo (23,3%). Se obtuvieron seis falsos positivos y tres falsos negativos. La sensibilidad de la prueba fue del 95,45% y la especificidad del 75%.Discusión. Se detecta una elevada tasa de falsos negativos, que podría explicarse por diferentes razones relacionadas con la obtención y la manipulación de la muestra (semana de gestación, técnica de extracción y técnica de amplificación).Conclusiones. La elevada tasa de falsos negativos en ladeterminación del RhD fetal a partir de sangre materna, que corresponde a casos susceptibles de aloinmunización materna y por tanto de desarrollar enfermedad hemolítica del feto recién nacido, obliga a una correcta reevaluación de la técnica empleada y de la interpre-tación de los resultados

Introduction. We evaluate the effectiveness in thedetermination of the foetal RhD from the mother’s blood.Material and methods. 90 Rh negative pregnant womenwith positive RhD couples allowed us, by signing aconsent form, to use their blood samples for this study. All these patients have been monitored in our centre from September 2004 to January 2006. The maternal blood samples were sent to the molecular biology laboratory for the quantification of exones 7 and 10 of the RhD’s gene. After that, the results obtained from the foetal RhD genotypes were compared with the phenotypes of the newborn’s RhD.Results. The results of the genotyping showed that69 (76,6%) of the foetuses were RhD positive, whereas 21(23,3 %) were RhD negative. The sensitivity of the testwas 95.45% and the specificity 75%. Six tests came outfalse positives and three false negatives.Discussion. Several factors related to the obtainingof the sample and the way it is manipulated (pregnancyweek, the extraction or amplification technique) couldexplain the high rate of false negatives.Conclusion. The high prevalence of false negativesdetected after a foetal RhD test on maternal blood forcesus to reconsider the used technique and to improve theway we interpret the results, taking into account thatthere is a risk of maternal isoimmunization and consequently an haemolytic disease on the newborn (AU)