J. Stirnemann

Long-term developmental follow-up of infants who participated in a randomized clinical trial of amniocentesis vs laser photocoagulation for the treatment of twin-to-twin transfusion syndrome

OBJECTIVEnWe sought to assess long-term neurodevelopment of children who were treated prenatally as part of the Eurofoetus randomized controlled trial.nnnSTUDY DESIGNnThe 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.nnnRESULTSnA 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).nnnCONCLUSIONnFSLC was significantly associated with a reduction of the risk of death or long-term major neurological impairment at the time of diagnosis and treatment.

Laser therapy for twin-to-twin transfusion syndrome (TTTS).

Monochorionic twins are subjected to specific complications which originate in either imbalance or abnormality of the single placenta serving two twins including twin‐to‐twin transfusion syndrome. The diagnosis is well established in overt clinical forms with the association of polyuric polyhydramnios and oliguric oligohydramnios. The best treatment of cases presenting before 26 weeks of gestion is fetoscopic laser ablation of the intertwin anastomoses on the chorionic plate. Although subjected to subtle variations, the core technique follows robust guidelines which could help understanding and acquiring the required skills and experience to perform this procedure. However appropriate and tailored hands‐on training and appropriate perinatal set‐up are critical not only for surgical management but also for the follow‐up and management of related complications. Copyright

Assessment of fetal Sylvian fissure operculization between 22 and 32 weeks: a subjective approach

Sylvian fissure operculization (SFO) is a dynamic process throughout gestation and is a reliable feature of fetal cortex gyration that is amenable to prenatal ultrasound examination. This study aimed to define a subjective and reproducible method for SFO assessment.

Prediction of Fetal Infection in Cases With Cytomegalovirus Immunoglobulin M in the First Trimester of Pregnancy: A Retrospective Cohort

BACKGROUNDnInterpretation 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.nnnMETHODSnA 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.nnnRESULTSnA 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).nnnCONCLUSIONnThis 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.

Active management of selective intrauterine growth restriction with abnormal Doppler in monochorionic diamniotic twin pregnancies diagnosed in the second trimester of pregnancy.

This study aims to compare outcomes of active management of monochorionic diamniotic twin pregnancies complicated with severe intrauterine growth restriction (IUGR) of one twin before 24u2009weeks with continuous or intermittent absent or reversed end‐diastolic flow (AREDF) in the umbilical artery, with or without twin‐to‐twin transfusion syndrome (TTTS).

Day-specific probabilities of conception in fertile cycles resulting in spontaneous pregnancies

STUDY QUESTIONnWhen, within the female cycle, does conception occur in spontaneously fertile cycles?nnnSUMMARY ANSWERnThis study provides reference values of day-specific probabilities of date of conception in ongoing pregnancies. The maximum probability of being within a 5-day fertile window was reached on Day 12 following the last menstrual period (LMP).nnnWHAT IS KNOWN ALREADYnThe true date of conception is not observable and may only be estimated. Accuracy of these estimates impacts on obstetric management of ongoing pregnancies. Timing of ovulation and fertility has been extensively studied in prospective studies of non-pregnant fertile women using error-prone proxies, such as hormonal changes, body-basal temperature and ultrasound, yielding day-specific probabilities of conception and fertile windows. In pregnant women, date of conception may be retrospectively estimated from early pregnancy fetal measurement by ultrasound.nnnSTUDY DESIGN, SIZE, DURATIONnRetrospective analysis of consecutive pregnancies in women referred for routine first-trimester screening, over a 3-year period (2009-2011) in a single ultrasound center (n = 6323).nnnPARTICIPANTS/MATERIALS, SETTING, METHODSnWithin the overall population, 5830 cases with a certain date of last menses were selected for analysis. The date of conception was estimated using a crown-rump length biometry and an equation derived from IVF/ICSI pregnancies. Day-specific probabilities of conception were estimated across several covariates, including age, cycle characteristics and ethnicity, using deconvolution methods to account for measurement error.nnnMAIN RESULTS AND THE ROLE OF CHANCEnOverall, the day-specific probability of conception sharply rises at 7 days after the LMP, reaching its maximum at 15 days and returning to zero by 25 days. Older women tend to conceive earlier within their cycle, as did women with regular cycles and white and black women compared with Asian ethnicity. The probability of being within the fertile window was 2% probability at Day 4, a maximum probability of 58% at Day 12 and a 5% probability by Day 21 of the cycle.nnnLIMITATIONS, REASONS FOR CAUTIONnAlthough conception is believed to occur within hours following ovulation, a discrepancy is theoretically possible. However, when comparing our results to those of prospective studies, no such difference was found. The equation used for estimating the date of pregnancy was estimated in IVF/ICSI pregnancies, which could lead to potential bias in spontaneous pregnancies. However, in our population, the observed bias was negligible. Non-fertile cycles and early pregnancy losses are necessarily overlooked because of the nature of our data.nnnWIDER IMPLICATIONS OF THE FINDINGSnBecause of the wider access to retrospective data and the potential bias in prospective studies of ovulation monitoring, this study should broaden the perspectives of future epidemiologic research in fertility and pregnancy monitoring.nnnSTUDY FUNDING/COMPETING INTERESTSnNone.

Feasibility of predicting the outcome of fetal infection with cytomegalovirus at the time of prenatal diagnosis

BACKGROUNDnCongenital 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.nnnOBJECTIVEnWe sought to evaluate the prognostic value of fetal ultrasound, amniotic fluid, and fetal blood analysis at the time of prenatal diagnosis of fetal infection.nnnSTUDY DESIGNnWe 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.nnnRESULTSnIn all, 82 fetuses were infected following maternal infection mainly in the first trimester. At the time of prenatal diagnosis at a median ofxa023 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/mm(3), and DNA load ≥4.93 log10 IU/mL in fetal blood were associated with a symptomatic status at birth in univariate analysis (P < .001, Pxa0= .001, and Pxa0= .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 valuexa0for 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.nnnCONCLUSIONnRisk 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.

Prenatal prediction of pulmonary arterial hypertension in congenital diaphragmatic hernia

To evaluate the role of prenatal prognostic markers obtained routinely by ultrasound examination and magnetic resonance imaging (MRI) in the prediction of development of postnatal pulmonary arterial hypertension (PAH) in isolated congenital diaphragmatic hernia (CDH).

Outcome following prenatal diagnosis of severe bilateral renal hypoplasia

The aim of this research was to evaluate the outcome and prognostic value of fetal serum β2‐microglobulin in case of prenatal diagnosis of severe bilateral renal hypoplasia.

Discordances Between Pre-Natal and Post-Natal Diagnoses of Congenital Heart Diseases and Impact on Care Strategies

BACKGROUNDnPre-natal diagnosis of congenital heart disease (CHD) allows anticipation of urgent neonatal treatment and provides adequate information to the parents on cardiac outcomes.nnnOBJECTIVESnThis 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.nnnMETHODSnWe 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.nnnRESULTSnFor 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.nnnCONCLUSIONSnCorrecting 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.