Clinical impact of Doppler reference charts on management of small-for-gestational-age fetuses: need for standardization.

OBJECTIVE: To assess clinical variability in the management of small-for-gestational-age (SGA) fetuses according to different published Doppler reference charts for umbilical artery (UA) and fetal middle cerebral artery (MCA) Doppler indices and cerebroplacental ratio (CPR). METHODS: We performed a systematic search of MEDLINE, EMBASE, CINAHL and the Web of Science databases from 1954 to 2018 for studies with the sole aim of creating fetal Doppler reference values for UA, MCA and CPR. The top cited articles for each Doppler parameter were included. Variability in Doppler values at the following clinically relevant cut-offs was assessed: UA-pulsatility index (PI) > 95th percentile; MCA-PI < 5th percentile; and CPR < 5th percentile. Variability was calculated for each week of gestation and expressed as the percentage difference between the highest and lowest Doppler value at the clinically relevant cut-offs. Simulation analysis was performed in a cohort of SGA fetuses (n = 617) to evaluate the impact of this variability on clinical management. RESULTS: From a total of 40 studies that met the inclusion criteria, 19 were analyzed (13 for UA-PI, 10 for MCA-PI and five for CPR). Wide discrepancies in reported Doppler reference values at clinically relevant cut-offs were found. MCA-PI showed the greatest variability, with differences of up to 51% in the 5th percentile value at term. Variability in the 95th percentile of UA-PI and the 5th percentile of CPR at each gestational week ranged from 21% to 41% and 15% to 33%, respectively. As expected, on simulation analysis, these differences in Doppler cut-off values were associated with significant variation in the clinical management of SGA fetuses, despite using the same protocol. CONCLUSIONS: The choice of Doppler reference chart can result in significant variation in the clinical management of SGA fetuses, which may lead to suboptimal outcomes and inaccurate research conclusions. Therefore, an attempt to standardize fetal Doppler reference ranges is needed. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

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.

[Proposal for a new microsurgical model for the study of induced endometriosis in Wistar rats. Preliminary results]. / Propuesta de un nuevo modelo microquirúrgico para el estudio de la endometriosis inducida en rata Wistar. Resultados preliminares.

The current knowledge status on the patogenesis of endometriosis as well as devastating consequences of disease evolution in women's reproductive health, have promoted researchers advances in a great manner during last years. The immunologic and neangiogenesis systems implication have opened new ways of knowledge over classic theories from the beginning of the xx century. The experimental resesearch, using animal induction models. Below we explain the first steps a new induction model ("PGR1-HotDog"), based on Wistar rats using a new disease autogeneration system, created for te study of the early stages of the endometriosis.

Propuesta de un nuevo modelo microquirúrgico para el estudiode la endometriosis inducida en rata Wistar. Resultados Preliminares / Proposal for a New Microsurgical Model for the Study of Induced Endometriosis in Wistar Rats. Preliminary Results

El desconocimiento actual sobre la patogenia de la endometriosis ylas devastadores consecuencias que conlleva esta enfermedad paralas mujeres en edad reproductiva, han sido las grandes promotorasde los esfuerzos de los investigadores en los últimos años. La implicaciónpatogénica del sistema inmunológico, así como de los procesosneoangiogénicos ha abierto una gran vía de conocimiento sobre lasteorías clásicas conocidas desde principios del siglo XX. Todo ello, pasapor la investigación experimental de la endometriosis, en modelosanimales, con sistemas de inducción de la enfermedad. A continuaciónexplicamos los primeros resultados de un nuevo modelo experimentalde autogeneración de endometriosis en rata Wistar (“PGR1-HotDog”),creado con una fi nalidad, el conocimiento de las fases más precocesde la enfermedad (AU)

The current knowledge status on the patogenesis of endometriosis aswell as devastating consequences of disease evolution in women´sreproductive health, have promoted researchers advances in a greatmanner during last years. The immunologic and neangiogenesis systemsimplication have opened new ways of knowledge over classic theoriesfrom the beginning of the XX century. The experimental resesearch,using animal induction models. Below we explain the fi rst steps a newinduction model (“PGR1-HotDog”), based on Wistar rats using a newdisease autogeneration system, created for te study of the early stagesof the endometriosis (AU)

[Effects of levofolinic acid on plasma homocysteine concentrations in healthy and young women in preconceptional care]. / Efecto del ácido levofolínico sobre las concentraciones de homocisteína plasmática en la mujer joven y sana en la consulta preconcepcional.

BACKGROUND: Increases in total plasmatic homocysteine (tHcy) represents a risk factor for neural tube defects. We studied the effects of levofolinic acid (l,5-formyl-tetrahydrofolic) on the plasmatic tHcylevels in women of child-bearing age. MATERIALS AND METHOD: Healthy women aged 18-35 years (n = 30) received levofolinic acid, 5 mg/day,orally for 30 days. Both tHcy and intraerythrocytic folate levels were measured before treatment (day 0), on days 2, 5, 10 and 30 within the treatment period and on days 30 (day 60) and 60 (day 90) after the treatment was finished. Plasmatic tHcy was measured by fluorescence polarisation immunoassay and intraerythrocyticfolates by chemiluminescent immunoassay. RESULTS: Plasmatic tHcy decreased from the second day of treatment onwards (day 0 vs. 2: mean of difference: -1.24 micromol/l; CI 95% = -0.84 to -1.63; p < 0.001). The maximum decline (32.3%) was observed after 30 days (mean of difference = -2.72 micromol/l; CI 95% = -2.20 to -3.24; p < 0.001).After finishing the treatment, the hypohomocysteinic effect persisted up to days 60 (mean of difference = -2.67 micromol/l; CI 95% = -2.07 to -3.26; p < 0.001)and 90 (mean of difference = -1.49 micromol/l; CI 95% = -0.94 to -2.03; p < 0.001). The response was greater when the plasmatic tHcy concentration was >= 9 micromol/l. CONCLUSIONS: Levofolinic acid leads to a earlier, intense and persistent drop of the plasmatictHcy levels.

Perinatal mortality in term and post-term births.

Our aim was to compare the fetal mortality rate (FMR), early neonatal mortality rate (ENMR) and perinatal mortality rate (PMR) of post-term and term births, 2) to examine trends in the incidence and perinatal mortality rates of post-term and term births. We used data from Spanish Perinatal Mortality Survey of 1980, 1986, 1989 and 1992. The data include 40,863 post-term births (42 weeks and over) and 517,060 term births (37-41 weeks). Perinatal mortality rates of post-term and term births were compared. The incidence of post-term births was 7.3%. The relative risk (RR) of FMR for post-term compared to term births was 1.1 (95% confidence interval [CI] 0.9-1.3), of ENMR was 1.6 (95% CI 1.4-2.0) and of PMR was 1.3 (95% CI 1.1-1.5). From 1980 to 1992 there was a significant reduction in the incidence of post-term births (8.1% vs 5.0%), in the FMR (4.5/1000 vs 1.9/1000), ENMR (4.3/1000 vs 2.0/1000) and PMR (8.7/1000 vs 3.9/1000) of post-term births. There was no significant difference in the FMR between post-term and term in each year studied. Post-term births had a significantly higher ENMR and PMR than term births in 1980, and they were equivalent from 1983 to 1992. The incidence of post-term births, its FMR, ENMR and PMR have been significantly reduced during the whole period studied.

Maternal leukocyte metabolism during pregnancy and puerperium, and its relation to fetal growth.

Changes of energy metabolism in maternal leukocytes were studied longitudinally in 33 normal term pregnancies at 12, 20 and 36 weeks of gestation and 40 days post partum. Nutrient intakes were calculated from 3-day weighed food records at the same periods. Women tended to decrease their mean dietary intakes of energy and of most nutrients from early to late pregnancy. Glucose-6-P dehydrogenase (G6P-DH), pyruvic kinase (PK) and adenylate kinase (AK) activities rose significantly after the 12th week of pregnancy, reaching maximal values at week 20. The following period up to week 36 showed a significant decrease that continued in the puerperium, when their values were lowest. Adenine nucleotide contents and protein/DNA ratio followed a different pattern. A significant increase was also observed from weeks 12 to 20, remaining without changes during the second half of gestation, and falling at puerperium. The PK and AK activities showed a positive correlation with energy intake at 36 weeks of gestation and AK activity was negatively correlated with folic acid intake in the middle of pregnancy. At week 20, PK activity showed a positive correlation with both head circumference and body mass index of the newborn. There was also a correlation between protein/DNA ratio and head circumference at the 36th week of gestation. These findings may suggest a relationship between the metabolism of maternal leukocytes, and fetal development in utero.

Perinatal mortality in twin pregnancy: an analysis of birth weight-specific mortality rates and adjusted mortality rates for birth weight distributions.

The objective of this study is to compare the fetal mortality rate (FMR), early neonatal mortality rate (ENMR) and perinatal mortality rate (PMR) of twin and single births. It is based on a survey which was carried out in 22 Hospital Centers in Spain in 1980, and covered 1,956 twins born and 110,734 singletons born. The FMR in twins was 36.3/1000 and 8.8/1000 for singletons. The ENMR in twins was 36.1/1000 and 5.7/1000 for singletons. The PMR in twins was 71.1/1000 and 14.4/1000 for singletons. When birthweight-specific PMR in twin and singletons births are compared, there were no differences between the rates for groups 500-999 g and 1000-1499 g. For birthweight groups of 1500-1999 g (124.4 vs 283.8/1000) and 2000-2999 g (29.6 vs 73.2/1000) the rates for twins were about twice lower than those for single births. The PMR for 2500 g and over birthweight was about twice higher in twins than in singletons (12.5 vs 5.5/1000). After we adjusted for birthweight there was a difference in the FMR (12.6 vs 9.8/1000) and the PMR (19.1 vs 16.0/1000, and no difference in the ENMR between twins and singletons (5.9 vs 6.4/1000), indicating that most of the differences among crude rates are due to differences in distribution of birthweight.