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Biomedical subjects

E Gratacós

Publications and source records attributed to E Gratacós.

At least 19 recordsLinked to original sources

Stage-dependent fetal umbilical blood flow changes induced by laser therapy and amniodrainage in twin-to-twin transfusion syndrome.

OBJECTIVE: To estimate changes in umbilical blood flow (UBF) and Doppler indices in pregnancies complicated by twin-to-twin transfusion syndrome (TTS) treated with either laser therapy or amniodrainage, and to evaluate the influence of the presence of hemodynamic deterioration prior to therapy, as determined by the Quintero stages of severity. METHODS: Forty-eight cases of TTS were included, and further classified into severity Stages I or II (absence of critically abnormal Dopplers (CAD), n = 22) and Stages III or IV (presence of CAD or hydrops fetalis, n = 26). In Stages I-II, 14 cases were treated with laser and eight with amniodrainage, and in Stages III-IV, 17 were treated with laser and nine with amniodrainage. Differences in the UBF, umbilical artery pulstility index (UA-PI) and ductus venosus pulsatility index (DV-PI) were estimated for both groups of severity before and after both treatments. Eleven normal monochorionic pregnancies were evaluated as controls. RESULTS: In recipients, UBF was significantly higher with respect to controls regardless of the stage, while donors had a significant decrease in UBF, but only in Stages III-IV. After laser treatment no changes were observed in fetuses in Stages I-II. In Stages III-IV, recipients showed a significant reduction in the DV-PI (mean DV-PI 1.31 +/- 0.18 vs. 1.05 +/- 0.22; P = 0.005) whereas donors showed a significant increase in the UBF (mean UBF 134 +/- 36 mL/min vs. 195 +/- 25 mL/min; P < 0.001) and in the DV-PI (mean DV-PI 0.99 +/- 0.26 vs. 1.36 +/- 0.42; P = 0.002), and a reduction in the UA-PI (mean UA-PI 1.86 +/- 0.41 vs. 1.58 +/- 0.30; P = 0.01). After amniodrainage only donor fetuses in Stages III-IV showed an increase in UA-PI (mean UA-PI 1.54 +/- 0.35 vs. 1.72 +/- 0.40; P = 0.015). No other changes were observed in any of the parameters studied. CONCLUSION: Laser therapy induces consistent hemodynamic variations in TTS mainly manifested in Stages III-IV.

Amniocentesis↗

A histological study of fetoscopic membrane defects to document membrane healing.

OBJECTIVE: To evaluate the rate of spontaneous healing in human fetal membranes after fetoscopy. STUDY DESIGN: Membranes from patients that had undergone fetoscopic interventions and delivered in one of the two treatment centers were included in the study. The membranes were examined macroscopically for any remaining defects and if present, the size of the defect in chorion and amnion was measured. Subsequently, the defect was excised and stained with HE for histological evaluation. Additional immunohistochemical staining was performed with Ki-67, cytokeratin and vimentin. The proliferation index (percentage of proliferating cells) was calculated in amnion and chorion. RESULTS: Nineteen membrane defects were included in the study. The median time interval between invasive procedures and delivery was 60 days (range 3-112). All fetoscopic defects (n=19) could be identified in the gestational sac and in none spontaneous closure had occurred. Proliferation indices as measured by inmunohistochemistry were very low (median 2.8%, range 0-7%) in the chorion and 0% in the amnion. CONCLUSION: No evidence of spontaneous membrane healing was found after fetoscopic procedures, suggesting that the membrane defect normally persists until delivery. Absence of amniotic fluid leakage after invasive procedures may be based on mechanisms other than histologic membrane repair.

Amnion↗

Incidence and characteristics of umbilical artery intermittent absent and/or reversed end-diastolic flow in complicated and uncomplicated monochorionic twin pregnancies.

OBJECTIVE: To evaluate the incidence and clinical relevance of intermittent absent and/or reversed diastolic flow on umbilical artery Doppler in different groups of monochorionic twin pregnancies. METHODS: This was a prospective study involving three groups of monochorionic pregnancies: Group 1: controls followed fortnightly from the first trimester (n = 80); Group 2: cases with selective intrauterine growth restriction (n = 40); and Group 3: cases with severe twin-twin transfusion syndrome (n = 50). The presence and persistence over time of intermittent absent and/or reversed end-diastolic flow on umbilical artery Doppler was recorded. Placentas were examined and placental sharing and the presence of large arterioarterial anastomoses (AAA) was assessed. Perinatal outcome was recorded in all cases. RESULTS: Intermittent absent and/or reversed diastolic flow was present in 5% (4/80) of cases in Group 1, 45% (18/40) in Group 2 and 2% (1/50) in Group 3 (P < 0.0001, Group 2 vs. 1 and 3). Placental examination was performed in 76.4% (130/170) of cases and sharing was 58% for Group 1, 81% for Group 2 and 73% for Group 3 (P < 0.0001, Groups 2 and 3 vs. 1). Large AAA were identified in all examined cases with intermittent flow (18/18) and in 3.6% (4/112) of those without. The in-utero mortality rate was 0% in Group 1 and in Group 2 fetuses without intermittent flow. However, it was 19.4% in Group 2 cases with intermittent diastolic flow. CONCLUSIONS: Intermittent absent and/or reversed end-diastolic flow may be considered to be a characteristic sign of monochorionic pregnancy, and seems to result from the existence of large AAA. Its incidence is significantly increased in the context of selective intrauterine growth restriction, indicating a high risk for poor pregnancy outcome in these cases.

Analysis of Variance↗

Prevalence of neurological damage in monochorionic twins with selective intrauterine growth restriction and intermittent absent or reversed end-diastolic umbilical artery flow.

OBJECTIVE: To assess the incidence of parenchymal lesions on early and late neonatal brain scans and its association with the presence or absence of intermittent absent or reversed end-diastolic umbilical artery flow velocity (A/REDV) in monochorionic twins complicated by selective intrauterine growth restriction (IUGR), as compared to dichorionic twins and monochorionic twins without selective IUGR. METHODS: This was a prospective cohort study involving 42 monochorionic twins diagnosed with selective IUGR and managed expectantly. The presence or absence of intermittent A/REDV was recorded in all cases. This study group was compared to dichorionic twins (n = 29) and monochorionic twins without selective IUGR (n = 32) delivered at 26-34 weeks during the study period. All infants underwent an early neonatal brain scan (at or before the fourth day of postnatal life) and at least one follow-up scan during the first 28 days of postnatal life. Perinatal outcome and the incidence of neurological damage were compared between the study groups. RESULTS: The incidence of intrauterine fetal death (IUD) and periventricular leukomalacia was significantly increased in monochorionic twins complicated with selective IUGR, as compared with the other study groups. Intermittent A/REDV was observed in 22/42 (52.4%) twin pairs, and was always present in the growth-restricted twin. The incidence of IUD (overall 9/44 (20.5%) vs. 0/40, P < 0.001; smaller twin 6/22 (27.3%) vs. 0/20, P < 0.05) and parenchymal brain damage (overall 7/35 (20.0%) vs. 2/40 (5.0%), P = 0.07; larger twin 7/19 (36.8%) vs. 1/20 (5.0%), P < 0.05) was significantly higher in pregnancies with intermittent A/REDV than in those without intermittent A/REDV. Brain damage usually occurred in the larger twin, irrespective of whether the smaller twin was liveborn or not. CONCLUSIONS: The presence of intermittent A/REDV in monochorionic twins with selective IUGR identifies a subgroup with an elevated risk of intrauterine demise of the smaller twin and neurological damage in the larger twin; this latter finding is not restricted to cases with IUD of the cotwin.

Birth Weight↗

Transient hydropic signs in the donor fetus after fetoscopic laser coagulation in severe twin-twin transfusion syndrome: incidence and clinical relevance.

OBJECTIVE: To evaluate the incidence, characteristics, and impact on perinatal outcome of the development of hydropic signs in the donor fetus after laser coagulation for severe twin-twin transfusion syndrome in the second trimester. METHODS: Forty cases of second-trimester severe twin-twin transfusion underwent fetoscopic laser coagulation of placental anastomoses and were followed up with serial ultrasound up to 14 days after therapy. Ultrasound scans were performed just before, and on days 1, 3, 5 and 14 after therapy, and fetuses were monitored for the presence of hydropic signs (skin edema, pleural effusion, ascites and pericardial effusion). Response to therapy and perinatal outcome in terms of neonatal survival were recorded for all cases. RESULTS: Four recipients (10%) and three donors (7.5%) died over the first 72 h after therapy. During the study period, two recipients (5.5%) developed frank hydrops fetalis, and eventually died in utero. Ten donors (27.0%) developed one or more hydropic signs. In nine (90%), signs were mild or moderate and transient (mean, 3.2 days), while in one case hydrops worsened and the fetus eventually died. No donors with transient hydrops died in utero, and two died postnatally due to extreme prematurity. Gestational age at procedure and deepest amniotic fluid vertical pocket were similar between hydropic and non-hydropic donors. Discrepancy in estimated fetal weight at procedure was significantly lower in donors developing hydrops (9.6 (SD, 6.4) vs. 17.8 (14.4)%,P = 0.018). In pregnancies with hydropic donors, gestational age at delivery (33.1 (3.4) vs. 29.7 (3.5) weeks,P = 0.015) and birth weight for recipient (2392 (423) vs. 1631 (576) g, P < 0.001) and donor (1908 (774) vs. 1281 (583) g,P = 0.021) were significantly higher. The development of transient hydrops had no influence on neonatal survival at 28 days nor on the rate of clinical resolution of intertwin transfusion. CONCLUSIONS: Transient hydropic signs may develop in a proportion of donor fetuses after laser coagulation for severe twin-twin transfusion syndrome. This phenomenon is normally not associated with a poor prognosis, and possibly indicates an hemodynamic adaptation response following interruption of the transfusion process.

Female↗

Impact of laser coagulation in severe twin-twin transfusion syndrome on fetal Doppler indices and venous blood flow volume.

OBJECTIVE: To evaluate the impact of fetoscopic laser coagulation of placental anastomoses in severe twin-twin transfusion syndrome on fetal Doppler indices and umbilical vein blood flow volume as calculated with Doppler and two-dimensional ultrasound. METHODS: Thirty-two cases of second-trimester severe twin-twin transfusion undergoing laser therapy were examined with serial ultrasound before and 1, 3 and 5 days after therapy. Pulsatility indices in the umbilical artery and ductus venosus were measured. Blood volume flow at the level of the intra-abdominal umbilical vein was calculated by means of Doppler and two-dimensional ultrasound. The development of hydropic signs in donors was recorded. Perinatal outcome in terms of neonatal survival was recorded for all cases. RESULTS: In recipients, ductus venosus pulsatility index decreased progressively after therapy and, by day 5, median pulsatility index was significantly lower than that before therapy (0.97 vs. 0.82, P < 0.0001). Umbilical vein blood flow volume in recipient twins showed no significant variations before and after laser. In donors, umbilical artery pulsatility index decreased significantly by the first day following therapy (2.1 vs. 1.6, P < 0.0001). Previously absent or reverse umbilical end-diastolic flow reappeared after therapy in 46% (7/15) of donors. Ductus venosus pulsatility index in donors increased significantly by day 1 after therapy (0.99 vs. 1.35, P < 0.0001) but, over days 3 and 5, it returned towards preoperative values. Umbilical vein flow volume measurements (mL/min/kg) in the donor increased by approximately 50% the day after treatment (151 vs. 232, P < 0.0001) and remained elevated. Umbilical vein flow volume before laser therapy was significantly lower in donors compared to recipients (151 vs. 260, P < 0.0001), but the difference was non-significant after treatment (240 vs. 267). One or more hydropic signs developed in eight (25%) donors during the 5 days' observation after therapy. CONCLUSIONS: Laser therapy induced important changes in fetal hemodynamic parameters, resulting in a reversion of the disturbances associated with severe twin-twin transfusion syndrome. The recipient twin showed a progressive improvement of previous signs of right cardiac overload. The donor experienced a substantial increase in umbilical vein blood volume flow accompanied by a transitory state of relative right overload, which may explain the development of transient hydropic signs in a proportion of donors.

Female↗

Effects of amniodistention with carbon dioxide on fetal acid-base status during fetoscopic surgery in a sheep model.

BACKGROUND: Because the data from previous experiments on the fetal effects of carbon dioxide (CO2) amniodistention in endoscopic fetal surgery are conflicting, we set out to evaluate the fetal acid-base status during CO2 amniodistention, with or without maternal hyperventilation, using a sheep model for endoscopic surgery. METHODS: We assigned 26 pregnant ewes undergoing amniodistention with CO2 (4-5 mmHg intraamniotic pressure) to one of the following three groups: group I had fetal surgery + no maternal hyperventilation (n = 10); group II had fetal surgery + maternal hyperventilation (n = 10); group III had no fetal surgery + maternal hyperventilation (n = 6). Hyperventilation kept CO2 at 29-31 mmHg; in its absence, pCO2 ranged from 38 to 41. Fetal surgery consisted of fetoscopic tracheal clipping. Maternal blood pressure (mean, 98/69 mmHg) and heart rate (mean, 72 bpm) were kept at values comparable to human pregnancy. Fetal and maternal blood gas measurements were taken every 15 min during 1 h of amniodistention. RESULTS: The ranges for baseline mean fetal pCO2 (mmHg) and pH were 51-55 and 7.24-7.25, respectively, in all study groups. After 1 h of amniodistention, mean +/- SEM values of fetal pCO2 and pH were 88 +/- 3 and 7.06 +/- 0.03 in group I, 69 +/- 4 and 7.13 +/- 0.02 in group II, and 71 +/- 5 and 7.14 +/- 0.04 in group III, respectively. Therefore, maternal hyperventilation attenuated but could not prevent significant fetal hypercarbia and acidosis. Fetal surgical manipulation had no effect on these observations. CONCLUSION: CO2 amniodistention should not be considered for clinical practice until ways of preventing its effects on the fetal acid-base status can be demonstrated.

Acid-Base Equilibrium↗

Serum antibodies to oxidized low-density lipoprotein in pregnant women with preeclampsia and chronic hypertension: lack of correlation with lipid peroxides.

OBJECTIVES: To evaluate the circulating levels of antibodies to oxidized low-density lipoprotein (LDL) and their correlation with the lipid peroxide/vitamin E ratio in pregnant women with preeclampsia and chronic hypertension. METHODS: Antibodies to oxidized LDL were measured by enzyme-linked immunoassay, lipid peroxides (malondialdehyde), and vitamin E were measured by high-pressure liquid chromatography. Patients were 25 healthy pregnant women, 20 previously nonhypertensive women diagnosed with preeclampsia, and 20 women with uncomplicated chronic hypertension. RESULTS: Serum levels of antibodies to LDL in preeclamptic patients were similar to controls, whereas women with chronic hypertension showed a trend for increased mean levels. Lipid peroxides in serum were significantly increased and vitamin E levels were significantly decreased in preeclampsia with respect to nonhypertensive pregnancy, but no differences were observed for chronic hypertensive women. CONCLUSIONS: Our results suggest that preeclampsia is not accompanied by increased levels of antibodies to oxidized LDL. By contrast, and according to previous studies in nonpregnant patients, chronic hypertensive patients showed a trend for elevated levels.

Antibodies↗

Successful sealing of fetoscopic access sites with collagen plugs in the rabbit model.

OBJECTIVE: The aim of this study was to evaluate the efficacies of various plugging techniques in sealing the membrane defect created by fetoscopy in the rabbit at midgestation. STUDY DESIGN: Fetoscopy was performed in pregnant rabbits at 23 days' gestation (term, 32 days' gestation). In group 1 fetal sacs were left unclosed (positive control group, n = 24). In group 2 injection with commercially available extracellular matrix (Matrigel; BD Labware, Bedford, Mass) was performed and a myometrial suture was inserted (n = 23). In group 3 the entry site was plugged with collagen (Colgen; Inter-Phar, Paris, France) combined with a myometrial suture (n = 22). At 30 days' gestation the membrane integrity, amniotic fluid presence, and fetal lung/body weight ratios were assessed. The plugging site was examined histologically. RESULTS: The use of suture and collagen plugs (group 3) resulted in functional restoration of membrane integrity with preservation of amniotic fluid and normal fetal lung/body weight ratio at term in 82% of cases, compared with 42% in the positive control group (group 1; P <.05). Histologic examination revealed entrapment of membranes between the plug and the myometrium but no anatomic repair of the membranes. The use of suture and extracellular matrix (group 2) did not achieve better results than those seen in group 1 (positive control group). CONCLUSION: Collagen plugs achieved functional sealing of fetoscopic access sites in a rabbit model and prevented oligohydramnios and pulmonary hypoplasia.

Amnion↗

Lipid-mediated endothelial dysfunction: a common factor to preeclampsia and chronic vascular disease.

Preeclampsia is a complex pathophysiological state where regulatory systems of inflammation and endothelial function are stimulated beyond the physiological limits of normal pregnancy. Different lines of evidence indicate that abnormal lipid metabolism is not a mere manifestation but is also involved in the pathogenesis of the disease. Lipid-mediated oxidative stress is likely to contribute to endothelial hyperstimulation leading to dysfunction and damage. Maternal predisposing factors seem to be essential to explain why some pregnant women develop a systemic syndrome such as preeclampsia and why others do not. Preliminary evidence suggests that abnormal lipid metabolism could be one of these factors. In this review the evidence for the contribution of lipid oxidation in the pathogenesis of preeclampsia, the similarities between preeclampsia and lipid-mediated chronic vascular disease will be summarized, and the reasons to believe that constitutional lipid abnormalities could be one of the maternal predisposing factors for developing the disease will be examined and will be discussed.

Endothelium↗

An organ-culture for in vitro evaluation of fetal membrane healing capacity.

OBJECTIVES: We aimed to set up an organ culture of human amniochorion to evaluate fetal membrane repair capacity following surgical trauma. METHODS: Fetal membranes were collected from four patients, during elective caesarean section at term. Explants were traumatised at the centre and cultured on collagen support material for a total of 12 days. Viability was assessed by light microscopy and proliferation by detection of 5-Bromo-2' deoxy-Uridine (BrdU) incorporation and immunohistochemistry. Wound healing capacity was assessed trough photographic documentation every 2 days. RESULTS: Cultures showed good survival for 12 days. Increased cellularity, survival and proliferations were observed at the borders of the cultures in contrast to the central trauma site. During the 12 days observation period, no significant closure of the membrane defect could be demonstrated. CONCLUSION: This organ culture system represents a new model for the study of human fetal membrane repair. Despite good survival and localised proliferation, no obvious closure of a surgically created defect was observed in the described culture conditions.

Extraembryonic Membranes↗

Current experience with fetoscopy and the Eurofoetus registry for fetoscopic procedures.

Fetoscopy has consolidated its position in fetal medicine, thanks to a combination of insight into the pathophysiology of selected conditions that are amenable to fetal surgery and the technical innovations in endoscopic equipment. In clinical practice, two types of fetoscopy can be discerned: Obstetrical Endoscopy and Endoscopic Fetal Surgery. The first involves surgical interventions on the placenta, umbilical cord and fetal membranes. Nd:YAG laser coagulation of placental vessels in case of feto-fetal transfusion syndrome and cord occlusion in monochorionic pregnancy are the most typical procedures. The second type addresses some rare fetal conditions requiring in utero surgery; most experience has been gathered with congenital diaphragmatic hernia. Endoscopic fetal surgery has a different historical and experimental background than obstetrical endoscopy, but they both share technical aspects as well as potential side effects. In this review, we aimed at bringing together currently available experience. We suggest that future developments of fetal endoscopic operations will involve a mixture of concepts from both fetoscopy types to reduce maternal invasiveness and complications, eventually improving acceptance by parents and doctors. We encourage the registration of all experience in a yet available open registry for prospective data collection, supported by the European Commission, with as primary target the assessment of maternal and fetal safety.

Databases, Factual↗

Is the angle of needle insertion influencing the created defect in human fetal membranes? Evaluation of the agreement between specialists' opinions and ex vivo observations.

OBJECTIVE: We sought to evaluate the agreement between the opinions of specialists in fetal medicine with ex vivo observations on the potential influence of the angle of needle insertion on the fluid leak through the created defect in human fetal membranes. STUDY DESIGN: Membranes from placentas of women who were delivered by elective cesarean were harvested, cut in pieces, and secured to the bottom of plastic tubes filled with Hartmann solution. They were punctured with 18-, 20-, or 22-gauge needles, with an angle of insertion of 90 degrees (group 1) or 45 degrees (group 2), and the flow rate (in milliliters per minute) through the created defect at a constant pressure of 150 mm H(2)O was measured. Fifty physicians performing amniocentesis at fetal medicine reference centers were interviewed about their impression and clinical attitude with respect to the angle of needle insertion at the time of amniocentesis. RESULTS: In the ex vivo study, puncture with a 45 degrees angle was associated with a significantly lower flow of fluid through the membrane defect for all needle sizes tested. Regarding survey answers, 82% of physicians try to perform amniocentesis with a given angle (ie, 90 degrees in the vast majority of cases). Among the reasons for doing so, minimizing membrane damage was mentioned in more than half of cases. CONCLUSION: These results provide evidence that the angle of needle insertion influences the type of defect and therefore the flow rate through human membranes. Membrane damage is a concern of a proportion of specialists while performing amniocentesis, but ex vivo observations do not agree with clinical assumptions on the potential influence of the angle of insertion.

Amniocentesis↗

Inhibin A serum levels in proteinuric and nonproteinuric pregnancy-induced hypertension: evidence for placental involvement in gestational hypertension?

OBJECTIVES: To evaluate the serum levels of inhibin A in pregnant women with different types of hypertension. METHODS: A case-control study, including 60 cases (20 women with preeclampsia, 20 with mild gestational hypertension, and 20 with chronic hypertension), and 60 gestational-age- and parity-matched controls. Inhibin A was measured in duplicate by enzyme-linked immunosorbent assay in serum samples frozen at -80 degrees C. RESULTS: As compared to controls, inhibin A levels were significantly elevated in women with preeclampsia ¿2.32 standard deviation (SD) 1.4¿ versus 0.50 (0.29) ng/mL, p < 0.001) and gestational hypertension [1.09 (0.73) versus 0.55 (0.29) ng/mL, p < 0.05], but not in the group of chronic hypertension [0.88 (0.69) versus 0.54 (0.39) ng/mL, p = 0.08]. Overlap in inhibin A values between cases and controls was observed in 20% (4/20) of women with preeclampsia and 55% (11/20) with gestational hypertension. CONCLUSIONS: Increased serum inhibin A may indicate that a proportion of mild nonproteinuric hypertension cases are associated with placental involvement.

Adult↗

Bipolar coagulation with small diameter forceps in animal models for in-utero cord obliteration.

The objective of this study was to evaluate the feasibility, efficacy and safety of bipolar coagulation using endoscopic forceps of diameters of 2.7 mm and less in animal models mimicking in-utero conditions. Forceps of 2.2, 2.3, 2.5 and 2.7 mm were tested in rabbits (n = 36). Vessel pairs were dissected and coagulated in a fluid environment under endoscopic vision at 15 and 25 W. The main outcome measure was the perforation rate. In fetal lambs (n = 25), umbilical cords were coagulated under sono-endoscopic control with power settings from 10 to 35 W. Main outcome measures were the duration of coagulation, perforation rate, change in the temperature of the amniotic fluid and efficacy of vessel occlusion rate. At 20-25 W, all cords were coagulated successfully without any perforation using 2.3, 2.5 or 2.7 mm forceps. Coagulation with the 2. 2 mm forceps was associated with a high perforation rate, although the design rather than the diameter of the forceps may have influenced this outcome. Bipolar coagulation with forceps between 2. 3 and 2.7 mm and appropriate power settings achieves efficacious and safe coagulation in animal models for umbilical cord occlusion.

Animals↗