Selective fetoscopic laser coagulation of the intertwin anastomotic chorionic vessels is the first-line treatment for twin-twin transfusion syndrome. However, in stage 1 twin-twin transfusion ...syndrome, the risks of intrauterine surgery may be higher than those of the natural progression of the condition.
This study aimed to compare immediate surgery and expectant follow-up in stage 1 twin-twin transfusion syndrome.
We conducted a multicentric randomized trial, which recruited from 2011 to 2018 with a 6-month postnatal follow-up. The study was conducted in 9 fetal medicine centers in Europe and the Unites States. Asymptomatic women with stage 1 twin-twin transfusion syndrome between 16 and 26 weeks’ gestation, a cervix of >15 mm, and access to a surgical center within 48 hours of diagnosis were randomized between expectant management and immediate surgery. In patients allocated to immediate laser treatment, percutaneous laser coagulation of anastomotic vessels was performed within 72 hours. In patients allocated to expectant management, a weekly ultrasound follow-up was planned. Rescue fetoscopic coagulation of anastomoses was offered if the syndrome worsened as seen during a follow-up, either because of progression to a higher Quintero stage or because of the maternal complications of polyhydramnios. The primary outcome was survival at 6 months without severe neurologic morbidity. Severe complications of prematurity and maternal morbidity were secondary outcomes.
The trial was stopped at 117 of 200 planned inclusions for slow accrual rate over 7 years: 58 women were allocated to expectant management and 59 to immediate laser treatment. Intact survival was seen in 84 of 109 (77%) expectant cases and in 89 of 114 (78%) (P=.88) immediate surgery cases, and severe neurologic morbidity occurred in 5 of 109 (4.6%) and 3 of 114 (2.6%) (P=.49) cases in the expectant and immediate surgery groups, respectively. In patients followed expectantly, 24 of 58 (41%) cases remained stable with dual intact survival in 36 of 44 (86%) cases at 6 months. Intact survival was lower following surgery than for the nonprogressive cases, although nonsignificantly (78% and 71% following immediate and rescue surgery, respectively).
It is unlikely that early fetal surgery is of benefit for stage 1 twin-twin transfusion syndrome in asymptomatic pregnant women with a long cervix. Although expectant management is reasonable for these cases, 60% of the cases will progress and require rapid transfer to a surgical center.
Abstract
Background
The known relationship between the gestational age at maternal primary infection an the outcome of congenital CMV is based on small, retrospective studies conducted between 1980 ...and 2011. They reported that 32% and 15% of cases had sequelae following a maternal primary infection in the first and second or the third trimester, respectively. We aimed to revisit this relationship prospectively between 2011 and 2017, using accurate virological tools.
Methods
We collected data on women with a primary infection and an infected child aged at least 1 year at the time of analysis. An accurate determination of the timing of the primary infection was based upon serial measurements of immunoglobulin (Ig) M and IgG and on IgG avidity in sera collected at each trimester. The case outcome was assessed according to a structured follow-up between birth and 48 months.
Results
We included 255 women and their 260 fetuses/neonates. The dating of the maternal infection was prospective in 86% of cases and retrospective in 14%. At a median follow-up of 24 months, the proportion of sensorineural hearing loss and/or neurologic sequelae were 32.4% (95% confidence interval CI 23.72–42.09) after a maternal primary infection in the first trimester, 0 (95% CI 0–6.49) after an infection in the second trimester, and 0 (95% CI 0–11.95) after an infection in the third trimester (P < .0001).
Conclusions
These results suggest that a cytomegalovirus infection can be severe only when the virus hits the fetus in the embryonic or early fetal period. Recent guidelines recommend auditory follow-ups for at least 5 years for all infected children. This raises parental anxiety and generates significant costs. We suggest that auditory and specialized neurologic follow-ups may be recommended only in cases of a maternal infection in the first trimester.
In this study, only children infected after a maternal primary infection in the first trimester had sequelae at follow-up. For women with seroconversion in the second or third trimester, the risk returns to the baseline associated with any pregnancy.
Abstract Background Pre-natal diagnosis of congenital heart disease (CHD) allows anticipation of urgent neonatal treatment and provides adequate information to the parents on cardiac outcomes. ...Objectives This study sought to analyze the discordances between expert fetal cardiac diagnosis and final diagnosis of CHD and their impact on neonatal and long-term care strategies. Methods We included 1,258 neonates with a pre-natally diagnosed CHD and 189 fetopsies following termination of pregnancy at our tertiary center over a 10-year period. Pre-natal echocardiographic and final diagnoses were compared. Results For live births, we identified 368 (29.3%) discordances between pre- and post-natal diagnoses. The pre-natal diagnosis was different from the post-natal diagnosis in 36 cases (2.9%) and partially different with a major impact on neonatal treatment of the CHD in 97 cases (7.7%). In 235 cases (18.7%), the diagnosis was partially different with no impact on neonatal planned treatment. The discordances had a negative impact on late care strategy in 62 cases (4.9%): more complex CHD that was unsuitable for biventricular repair, leading to unplanned compassionate care, additional surgery or increase of the complexity level of the Aristotle score. A positive impact was found in 31 cases (2.5%): less complex CHD that allowed biventricular repair, fewer surgical procedures, or decrease of the complexity of the Aristotle score. For 275 patients (21.9%), there was no impact on late care strategy. Of the 872 terminations of pregnancy and intrauterine fetal deaths, 189 fetopsies were available: 16 (8.5%) different diagnoses, 27 (14.3%) major differences, and 60 (31.7%) minor differences. Conclusions Correcting fetal cardiac diagnosis after birth can lead to significant changes in neonatal (10.6%) and late (7.4%) care strategies. Tools should be developed to try to improve the accuracy of pre-natal diagnosis of CHD. Clinicians should be cautious when predicting required treatment and outcomes during pre-natal counseling.
Background Evaluation of trainee’s ability in obstetrical ultrasound is a time-consuming process, which requires involving patients as volunteers. With the use of obstetrical ultrasound simulators, ...virtual reality could help in assessing competency and evaluating trainees in this field. Objective The objective of the study was to test the validity of an obstetrical ultrasound simulator as a tool for evaluating trainees following structured training by comparing scores obtained on obstetrical ultrasound simulator with those obtained on volunteers and by assessing correlations between scores of images and of dexterity given by 2 blinded examiners. Study Design Trainees, taking the 2013 French national examination for the practice of obstetrical ultrasound were asked to obtain standardized ultrasound planes both on volunteer pregnant women and on an obstetrical ultrasound simulator. These planes included measurements of biparietal diameter, abdominal circumference, and femur length as well as reference planes for cardiac 4-chamber and outflow tracts, kidneys, stomach/diaphragm, spine, and face. Images were stored and evaluated subsequently by 2 national examiners who scored each picture according to previously established quality criteria. Dexterity was also evaluated and subjectively scored between 0 and 10. The Raghunathan’s modification of Pearson, Filon’s z, Spearman’s rank correlation, and analysis of variance tests were used to assess correlations between the scores by the 2 examiners and scores of dexterity and also to compare the final scores between the 2 different methods. Results We evaluated 29 trainees. The mean dexterity scores in simulation (6.5 ± 2.0) and real examination (5.9 ± 2.3) were comparable ( P = .31). Scores with an obstetrical ultrasound simulator were significantly higher than those obtained on volunteers ( P = .027). Nevertheless, there was a good correlation between the scores of the 2 examiners judging on simulation ( R = 0.888) and on volunteers ( R = 0.873) ( P = .81). Conclusion An obstetrical ultrasound simulator is as good a method as volunteer-based examination for evaluating practical skills in trainees following structured training in obstetrical ultrasound. The threshold for success/failure should, however, be adapted as candidates obtain higher scores on the simulator. Advantages of the obstetrical ultrasound simulator include the absence of location and time constraints without the need to involve volunteers or to interfere with the running of ultrasound clinics. However, an obstetrical ultrasound simulator still lacks the ability to evaluate the trainees’ ability to interact with patients.
Given the maternal morbidity of open fetal surgery, the development of prenatal fetoscopic repair for spina bifida aperta (SBA) is encouraged.
We hereby report the early results from our center, ...using a laparotomy-assisted CO2-fetoscopic approach.
This study was conducted in patients with an SBA < T1 and >S1, <26 weeks of gestation, with Chiari II. Fetoscopic repair was performed using 2 operating trocars in the uterus exteriorized through a transverse laparotomy. Endoscopy was performed under humidified and heated CO2 insufflation. Following dissection of the lesion, a 1-layer approach was performed with a muscle/skin flap sutured over a patch of Duragen. Main outcomes were watertight repair at birth and the need for postnatal neurosurgical surgery including shunting within 6 months.
Of 87 women assessed for prenatal therapy, 7 were included. Surgery was performed at 24 (23-26) weeks' gestation. There was no fetal demise. Conversion to hysterotomy was not performed, although surgery could not be performed in 1 case because of fetal position. Severe preeclampsia developed postoperatively in 1 case. In the other 6 cases, follow-up was uneventful except for premature rupture membranes which occurred in 3/6 cases at 30, 34, and 36+5 weeks' gestation. Gestational age at delivery was 32 + 5 (31-36 + 5) weeks' gestation. Repair was watertight at birth except in 2 cases which required complementary postnatal surgical repair. Reverse hindbrain herniation during pregnancy was observed in 4/6 cases. In 3/6 cases, shunting was necessary within 6 months after birth. At 12 months, a functional gain of ≥2 metameric levels was observed in 3 cases of the 6 survivors.
Laparotomy-assisted fetoscopic repair is a reasonable option for women who choose and are eligible for antenatal surgery, both in terms of maternal and perinatal morbidity.
Background. Interpretation of positive cytomegalovirus (CMV) immunoglobulin M (IgM) in the first trimester of pregnancy is ill-defined. We aimed to quantify the risk of fetal transmission in women ...with positive CMV IgM in the first trimester. Methods. A retrospective cohort of women (2009–2011) was tested for CMV immunoglobulin G (IgG) and IgM before 14 weeks of gestation. IgG avidity was tested with 2 assays (LIAISON and VIDAS). CMV polymerase chain reaction (PCR) was done in maternal serum, amniotic fluid, or neonatal urine at birth. Results. A total of 4931 consecutive women were screened; 201 presented with positive or equivocal IgM and with high, intermediate, or low IgG avidity in 58.7%, 18.9%, and 22.3%, respectively. In 72 women with low or intermediate avidity, fetal transmission was 23.6%. In multivariate analysis, positive CMV PCR in maternal serum, decreasing avidity index with both LIAISON and VIDAS, and low IgG titers were all associated with fetal transmission (odds ratio OR, 12.38 95% confidence interval {CI}, 1.77–86.33, P = .011; OR, 0.16 95% CI, .03–.95, P = .044; OR, 0.54 95% CI, .11–.88, P = .028; and OR, 0.27 95% CI, .29–.84, P = .010, respectively). Conclusion. This study demonstrates a significant association between the risk of vertical transmission and the avidity index combined with CMV PCR in maternal serum or IgG titers. This allows calculation of incremental risk of fetal transmission upon which informed choice can be based and could lead to a better pickup rate of fetal infection while decreasing unnecessary invasive procedures.
Background Congenital cytomegalovirus infection occurs in 0.7% of live births with 15-20% of infected children developing long-term disability including hearing loss and cognitive deficit. Fetal ...cytomegalovirus infection is established by viral DNA amplification by polymerase chain reaction in amniotic fluid obtained by amniocentesis following maternal seroconversion or after the diagnosis of ultrasound features suggestive of fetal infection. Severe brain ultrasound anomalies are associated with a poor prognosis. The prognosis of an infected fetus showing either no ultrasound features or nonsevere ultrasound anomalies is difficult to establish up until late in the second or third trimester of pregnancy. Objective We sought to evaluate the prognostic value of fetal ultrasound, amniotic fluid, and fetal blood analysis at the time of prenatal diagnosis of fetal infection. Study Design We reviewed all cases of fetal cytomegalovirus infection with a sample of amniotic fluid positive for viral DNA and/or fetal blood analyzed in our laboratory from 2008 through 2013. Prenatal ultrasound features along with cytomegalovirus DNA loads in amniotic fluid and in fetal blood and fetal platelet counts were reviewed in relation to gestational age at maternal infection, neonatal examination, and postnatal follow-up or postmortem examination. Results In all, 82 fetuses were infected following maternal infection mainly in the first trimester. At the time of prenatal diagnosis at a median of 23 weeks, 19, 22, and 41 fetuses showed severe brain ultrasound abnormalities, nonsevere ultrasound features, and normal ultrasound examination, respectively. Nonsevere ultrasound features, higher DNA load in amniotic fluid, fetal platelet count ≤114,000/mm3 , and DNA load ≥4.93 log10 IU/mL in fetal blood were associated with a symptomatic status at birth in univariate analysis ( P < .001, P = .001, and P = .018, respectively). Bivariate analysis combining ultrasound results and either adjusted viral load in amniotic fluid or fetal blood profile showed that these were independent prognostic factors of a symptomatic status at birth. Both fetal blood parameters were better predictors than amniotic fluid viral load. At the time of prenatal diagnosis, the ultrasound negative predictive value for symptoms at birth or at termination of pregnancy was 93%. The combined negative predictive values of ultrasound and viral load in amniotic fluid and that of ultrasound and fetal blood parameters were 95% and 100%, respectively. In fetuses presenting with nonsevere ultrasound features, the positive predictive values of ultrasound alone and in combination with amniotic fluid viral load or with fetal blood parameters were 60%, 78%, and 79%, respectively. Conclusion Risk assessment of infected fetuses for being symptomatic at birth is possible as early as the time of diagnosis by using a combination of targeted ultrasound examination along with viral load in amniotic fluid and in fetal blood together with platelet count. The advantage of using amniotic fluid is that it is available at prenatal diagnosis. One may wonder if increasing the negative predictive value of the overall assessment of an infected fetus from 95-100% is worth the additional risk of cordocentesis for fetal blood sampling. This can only be an individual decision made by well-informed women and it seems therefore appropriate to use the figures presented here and their confidence intervals for counseling.
Objective We sought to assess long-term neurodevelopment of children who were treated prenatally as part of the Eurofoetus randomized controlled trial. Study Design The study population was composed ...of 128 cases of twin-to-twin transfusion syndrome (TTTS) included and followed up in France. Survivors were evaluated by standardized neurological examination and by Ages and Stages Questionnaires (ASQ). Primary outcome was a composite of death and major neurological impairment. Results A total of 120 children (47%) were alive at the age of 6 months and were followed up to the age of 6 years. At the time of diagnosis, only treatment and Quintero stage were predictors of a poor outcome (hazard ratio, 0.61; 95% confidence interval, 0.41–0.90; P = .01 and hazard ratio, 3.23; 95% confidence interval, 2.19–4.76; P < .001, respectively). Children treated by fetoscopic selective laser coagulation (FSLC) had higher ASQ scores at the end of follow-up ( P = .04). Conclusion FSLC was significantly associated with a reduction of the risk of death or long-term major neurological impairment at the time of diagnosis and treatment.
Monochorionic twin pregnancies are at increased risk for adverse outcome compared to dichorionic twin pregnancies and singletons. Monochorionic-specific complications include twin–twin transfusion ...syndrome (TTTS), twin anemia–polycythemia sequence, single intrauterine fetal demise and its consequences on the co-twin, and selective intrauterine growth restriction. Whereas the natural history of monochorionic-specific complications carries a high risk of fetal death or severe neurologic disability, a framework now exists, based on well-designed clinical trials, for optimal treatment of these entities. Fetoscopic selective laser coagulation of anastomotic vessels on the chorionic plate has been clearly demonstrated to improve survival and neurologic outcomes for Quintero stage ≥2 TTTS. However, many challenges remain unsolved, the most important of which is preterm premature rupture of membranes. Further improvement in the outcomes of monochorionic pregnancies will require improvements in the rate of premature delivery, and improved diagnosis and treatment strategies for early and late onset TTTS.
Objective Prenatal screening for aneuploidies is best achieved in the first trimester when there is no reliable screening test for spina bifida. Early ultrasound features may be too complex for ...routine screening. We assessed screening potential of simple and reproducible fetal biometric measurements at 11-14 weeks of gestation. Study Design A total of 34,951 unselected consecutive pregnancies included 18 with spina bifida. Another 28 cases were referred for assessment. Biometric measurements were expressed in multiples of the median for crown-rump length. Results Biparietal diameter (BPD) was smaller in spina bifida ( P < .0001). In all, 22 of 44 (50%) cases with spina bifida aperta had a BPD <5th centile. BPD was independent of maternal adiposity and smoking status. Conclusion Simple and reproducible BPD at 11-14 weeks of gestation could detect half the cases of open fetal spina bifida by identifying 5% of pregnancies for expert scanning in first- and second-trimester examinations of the fetal spine and cranium.
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