Elisa Done

Objective: Fetoscopic endoluminal tracheal occlusion (FETO) may improve outcome of severe isolated congenital diaphragmatic hernia (iCDH). We aimed to identify any discrepancy between initial assessment at the referring hospital and the evaluation at the fetal surgery center, and to document parental decisions following counseling for fetal surgery.Design: Single center retrospective study on patients with presumed iCDH either referred for assessment and counseling or referred for fetal surgery. Discordant findings were defined as either a >10% difference in lung size, discordant liver position or associated anomalies.Results: Outcomes from 129 consecutive assessments over 24 months were analyzed. Among fetal surgery referrals, 2% did not have CDH, and 10% had undiagnosed associated anomalies. Liver position was discordant in 7%. Thirty‐three per cent had discordant lung size. Ninety‐four per cent of patients eligible for surgery underwent FETO. In patients referred because of suspicion of CDH, associated anomalies were found in 14%. Fetal liver and lung assessments were discordant in 50% resp. 38%. Of those patients eligible for FETO, 26% requested termination. For three patients, the postnatal course was marked by a genetic or syndromic additional diagnosis.Conclusion: Discordances between initial assessment before referral and evaluation in our institution were frequent, some of them clinically relevant. © 2017 John Wiley & Sons, Ltd.

STUDY QUESTION Does the manipulation of gametes or embryos during ARTs increase the risk for monozygotic twinning (MZT)? SUMMARY ANSWER Frozen embryo transfer (ET) is associated with a lower MZT rate, while blastocyst culture is associated with an increased risk of monozygotic pregnancy. WHAT IS KNOWN ALREADY Monozygotic twins have a higher risk for perinatal complications. Although an increased incidence of monozygotic pregnancies after ART has been previously reported, data regarding the possible impact of different laboratory procedures are conflicting. STUDY DESIGN, SIZE, DURATION All clinical pregnancies after single ET carried out in our centre between 2004 and 2013 (n = 6096) were retrospectively analysed for the incidence of MZT. The effect of different laboratory procedures on the incidence of MZT was evaluated. PARTICIPANTS/MATERIALS, SETTING, METHODS The following ART risk factors were assessed: maternal age, type of ET (fresh versus frozen), zona pellucida (ZP) manipulation (specifically, ICSI, embryo biopsy and assisted hatching), use of donor oocytes, embryo stage at time of ET (cleavage, compaction, early or advanced blastocyst) and culture media. MAIN RESULTS AND THE ROLE OF CHANCE The overall MZT rate was 2.2% (136/6096). Frozen ET was associated with a significant reduction in MZT incidence (adjusted odds ratio (aOR) 0.48, 95% CI 0.29–0.80), while blastocyst transfer (early or advanced blastocyst) was associated with a significant increase in MZT risk (aOR 2.70, 95% CI 1.36–5.34; aOR 2.05, 95% CI 1.29–3.26, respectively). No significant differences were found between the MZT and singleton (non-MZT) groups regarding maternal age, the use of different ZP manipulation techniques, not type of culture media used. LIMITATION, REASONS FOR CAUTION This study is limited by its retrospective nature and the fact that monozygosity was not confirmed by genetic testing. Furthermore, since monozygotic pregnancy is a rare event, other ART parameters that may influence its incidence could not be assessed during our analysis. WIDER IMPLICATION OF THE FINDINGS Our findings warrant future studies designed to investigate the association between specific ART procedures and MZT, namely the potential risk of blastocyst transfer to increase MZT. STUDY FUNDING/COMPETING INTEREST(S) No external funding was used for this study. There are no conflicts of interest.

Objective: To correlate prenatal indicators of pulmonary hypoplasia with neonatal lung function and pulmonary hypertension (PHT) in isolated congenital diaphragmatic hernia (iCDH). Materials and Methods: Prospective single-center study on 40 fetuses with iCDH either expectantly managed (n = 13) or undergoing tracheal occlusion (n = 27). Prenatal predictors included observed/expected lung-head ratio (O/E LHR), observed/expected total fetal lung volume, fetal pulmonary reactivity to maternal O₂ administration (pulsatility index, PI) and liver-to-thorax ratio (LiTR) as measured in the second and third trimesters. Postnatal outcome measures included survival until discharge, best oxygenation index (OI) and alveolar-arterial oxygen gradient [D(A-a)O₂] in the first 24 h of life and the occurrence of PHT in the first 28 days of life. Results: Median gestational age (GA) at evaluations was 27.2 and 34.3 weeks. GA at delivery was 36.0 weeks, and overall survival was 55%. In the second trimester, measurement of lung size, LiTR and pulmonary reactivity were significantly related to survival and the best OI and D(A-a)O₂.The occurrence of PHT was better predicted by PI and LiTR. Conclusions: O/E LHR, LiTR and vascular reactivity correlate with ventilatory parameters in the first 24 h of life. Occurrence of PHT at ≥28 days was best predicted by LiTR and PI, but not by lung size.

Objective: To explore the psychosocial impact of invasive fetal therapy (FT).Methods: We studied 100 consecutive patients scheduled for invasive FT. Contemporary controls were women undergoing (1) invasive prenatal diagnosis (AC/CVS) and (2) first trimester risk assessment of aneuploidy (NT), and (3) women who declined the latter (CTR). Prior to the procedure, participants completed the Beck Depression Inventory II, the State‐Trait Anxiety Inventory, the Dyadic Adjustment Scale and a questionnaire specifically designed to evaluate the process preceding the intervention.Results: Thirty‐five percent of women in the FT group had mild to severe depressive symptoms, and 30% showed high levels of state anxiety. Mean state anxiety was significantly higher in women facing invasive as compared to non‐invasive procedures. Trait anxiety levels and relationship scores were comparable across all groups. FT patients were more satisfied with the information and support given, whereas women in the NT group felt a greater degree of self‐determination and contentedness with the choices they made.Conclusion: Pregnant women awaiting invasive prenatal diagnosis and FT face higher levels of state anxiety than women undergoing non‐invasive procedures. Traits of depression and high state anxiety are found in at least one third of women undergoing FT. © 2013 John Wiley & Sons, Ltd.

Objective: This study aimed to establish nomograms for sonographic assessment of fetal pulmonary vascular reactivity following maternal hyperoxygenation.Study design: Sixty‐two healthy fetuses were assessed at four weekly intervals from 26 weeks onwards. Pulmonary reactivity was evaluated using Doppler ultrasound in the main pulmonary artery and in the first branch of this main pulmonary artery. The difference in pulsatility index (∆PI) during maternal inhalation of a mixture of room air and oxygen (9 L/min) for at least 10 min was expressed as a percentage. Nomograms were constructed, and Kaplan–Meier curves were used to express the occurrence of a reactive test (∆PI ≥ 20%) with advancing gestation.Results: In the first branch, linear regression analysis revealed a significant correlation of ∆PI (%) with gestational age (r² = 0.04, p = 0.0057). Large inter‐individual and intra‐individual variability was noted. The ∆PI (%) in the main pulmonary artery remained constant throughout gestation (6.62 ± 17.83%).Conclusion: Vascular reactivity in the pulmonary circulation increases in the first branch of the pulmonary artery. Large individual variability is limiting its use as a management tool. © 2012 John Wiley & Sons, Ltd.

Objectives: To predict neonatal survival and pulmonary hypertension by measurement of fetal pulmonary artery reactivity to maternal hyperoxygenation in fetuses with severe congenital diaphragmatic hernia treated by fetoscopic endoluminal tracheal occlusion (FETO).Methods: Thirty‐eight fetuses underwent FETO at around 28 weeks' gestation and the balloon was removed at 34 weeks in most cases. We performed a hyperoxygenation test and measured the lung‐to‐head ratio of each fetus before and after each procedure. Outcome measures were neonatal survival, occurrence of pulmonary hypertension and its response to inhaled nitric oxide (iNO).Results: Fetuses that survived had a larger increase in lung size and decrease of resistance in the first branch of the main pulmonary artery than did those that died. Both measures were also predictive of pulmonary hypertension unresponsive to iNO. The hyperoxygenation test and lung‐to‐head ratio were both best predictive for neonatal survival when measured following removal of the balloon (P < 0.002). Discriminant analysis confirmed that these two parameters are independent predictors of outcome.Conclusions: In fetuses undergoing FETO, pulmonary vascular reactivity in relation to oxygen and lung size are independent predictors of neonatal survival and pulmonary hypertension. The hyperoxygenation test merits further study in expectantly managed cases. Copyright © 2011 ISUOG. Published by John Wiley & Sons, Ltd.

Purpose: In fetuses with isolated congenital diaphragmatic hernia (CDH), lung development can be measured by the lung-to-head ratio (LHR) using ultrasound as well as by lung volumetry determined by fetal magnetic resonance imaging (MRI). We aimed to investigate their relationship as well as to analyze the factors that may have an impact on it. Material and Methods: In 153 consecutive fetuses with isolated CDH, both the LHR and total fetal lung volume (TFLV) were measured. The observed LHR was calculated by dividing the lung area by the head circumference. On MRI, planimetric measurements of ipsilateral, contralateral and TFLV were performed on T₂-HASTE (half-Fourier acquisition single-shot turbo spin echo) sequences in transverse as well as coronal or sagittal planes. All values were expressed as a ratio of what was observed over what is expected in a gestational age-matched normal fetus. Secondary analyses were performed for right- versus left-sided hernia and for measurements made prior to 25 weeks’ gestation. A multivariate linear regression approach was used to determine the influence of the independent variables such as observed/expected (O/E) LHR, gestational age, liver position and CDH side on the dependent variables O/E TFLV and O/E contralateral FLV, and to determine the optimal formulas for calculation of the O/E TFLV as well as contralateral FLV. Results: In total, 200 pairs of measurements were obtained between 20 and 37 weeks’ gestation (median 26+6). There was a significant association between the O/E contralateral FLV and O/E LHR (R² = 0.44; p < 0.001) as well as between the O/E TFLV and the O/E LHR (R² = 0.37; p < 0.001). After adding the independent variables that were first shown to be significant on univariate analysis, the multiple regression analysis demonstrated that gestational age (p = 0.017) and side of the defect (p < 0.001) were predictive of O/E LHR (p < 0.001) and strongly improved the estimation of O/E TFLV (R² = 0.43 instead of 0.37 when using O/E LHR only). In terms of estimating O/E contralateral FLV, only the O/E LHR was a significant (p < 0.001) independent predictor (R² = 0.44). These correlations also applied when considering only left-sided CDH cases. For measurements done prior to the third trimester, the O/E LHR (p = 0.034), gestational age (p = 0.035) as well as liver herniation (p = 0.029) were significantly correlated to the O/E TFLV (R² = 0.33). In terms of predicting the O/E contralateral FLV (R² = 0.25), only O/E LHR (p = 0.008) and gestational age (p = 0.037) were useful predictors. Conclusion: Measurement of the O/E LHR on ultrasound allows a good estimation of the O/E contralateral FLV as well as TFLV as measured by MRI. Whereas the additional parameters such as gestational age, liver position and side of the defect did not improve the estimation of the contralateral FLV, they did so for estimating the TFLV.

Objective: The aim of this study was to identify predictors of twin‐to‐twin transfusion syndrome (TTTS) and selective intrauterine growth restriction (sIUGR) in monochorionic diamniotic (MCDA) twin pregnancies with moderate amniotic fluid discordance (mAFD).Methods: Monochorionic twins with mAFD (n = 45; gestational age, 15–29 weeks) were assessed for extent of fluid discordance, fetal growth discordance and fetal cardiac dysfunction, and were followed longitudinally. A prediction algorithm was constructed for TTTS and sIUGR and validated in an unrelated cohort (n = 52).Results: Cardiac dysfunction could not predict TTTS or sIUGR. Twins below 20 weeks of gestation with a fluid discordance of ≥ 3.1 cm had a risk of TTTS of 85.7%. Sensitivity for TTTS was nevertheless only 55%. An intertwin weight discordance of ≥ 25% had 63% sensitivity and 76% specificity for sIUGR without TTTS.Conclusion: The outcome of MCDA twins with mAFD remains unpredictable, yet high‐risk and low‐risk subgroups for TTTS can be identified based on severity of fluid discordance and gestational age. Copyright © 2011 ISUOG. Published by John Wiley & Sons, Ltd.