Intertwin discordance of aldosterone levels in amniotic fluid with placental anastomoses in monochorionic twins: Insight into the pathophysiology of twin-to-twin transfusion syndrome.

INTRODUCTION: Our objective was to investigate the association between the presence of placental anastomoses and intertwin differences in renin-angiotensin-aldosterone activation in monochorionic twins using amniotic fluid aldosterone (AF-ALD) levels. In addition, this study also examined the association between AF-ALD and the ALD levels in the umbilical cord blood (UCB-ALD) in monochorionic twins. MATERIAL AND METHODS: This prospective study included monochorionic diamniotic (MD) twin pregnancies that were not complicated by twin-to-twin transfusion syndrome (TTTS) at delivery. Amniotic fluid and umbilical cord vein blood samples were collected from each twin at delivery, and the ALD levels were measured subsequently. The MD twins were divided into two groups: those with placental anastomoses and those without anastomoses owing to fetoscopic laser surgery. The differences in the AF-ALD levels between the larger and smaller twins were analyzed. RESULTS: The AF-ALD levels showed a strong and significant positive correlation with UCB-ALD levels in 131 MD twins (r = 0.804, p < 0.001). Intertwin differences were examined in 41 and 28 pairs of MD twins with and without placental anastomoses, respectively. The AF-ALD levels in the smaller twins were significantly higher than those in the larger twins among the pairs of MD twins with placental anastomoses (p = 0.003); however, no statistically significant intertwin differences were observed among the twins without placental anastomoses (p > 0.05). CONCLUSIONS: The AF-ALD levels reflect the UCB-ALD levels in MD twins. The presence of placental anastomoses led to intertwin discordance in the ALD levels in MD twins even uncomplicated with TTTS. It was considered that monochorionic twins have this clinical background, and it leads to the development of TTTS.

Sensitive detection of hemodynamic changes after fetoscopic laser photocoagulation by assessing intraventricular pressure difference in fetuses with twin-to-twin transfusion syndrome.

OBJECTIVES: To assess the hemodynamics of twin-to-twin transfusion syndrome (TTTS), we measured the intraventricular pressure difference (IVPD), a sensitive marker of myocardial diastolic function, using fetal echocardiography. METHODS: We included 28 monochorionic diamniotic (MD) twins diagnosed with TTTS who underwent fetoscopic laser photocoagulation (FLP) between 2018 and 2022. Color M-mode Doppler images of both cardiac ventricles were obtained before and after FLP. According to this evaluation, the IVPDs were divided into three groups; those with total, basal, and mid-apical IVPD. RESULTS: Of the 28 twins, 21 were available for analysis (including eight, eight, three, and two cases in stages Quintero Ⅰ, Ⅱ, Ⅲd, and Ⅲr, respectively). Comparing the pre and postFLP results, significant increases in total and mid-apical IVPD in the left ventricle (LV) of recipient twins were noted (total and mid-apical IVPD: p=0.026 and 0.013, respectively). In the LV of the donor twins, all IVPDs were significantly increased after FLP (total, basal, and mid-apical IVPD: p=0.003, 0.001, and 0.022, respectively). In addition, comparisons between the donor and recipient groups did not show significant differences in either ventricle before FLP. CONCLUSIONS: IVPD detected subtle hemodynamics changes, such as volume overload and diastolic dysfunction in TTTS before and after FLP. Therefore, IVPD may be a useful marker for monitoring myocardial diastolic function in TTTS.

Different expressions of cardiac biomarkers between different types of acquired right ventricular outflow tract abnormality in monochorionic twins.

OBJECTIVE: To investigate the differences in amniotic fluid cardiac biomarkers and clinical features among types of right ventricular outflow tract (RVOT) abnormality in monochorionic (MC) twins. METHOD: This prospective study included MC twins that underwent laser surgery. Recipient or larger twins (group A) and donor or smaller twins (group B) were assessed and divided into those with a normal right ventricular outflow tract (normal RVOT), functional pulmonary atresia (fPA), or pulmonary stenosis (PS). Amniotic fluid levels of NT-proBNP (afNT-proBNP) and cardiac troponin T (afTnT) were examined during surgery. RESULTS: Of 190 fetuses in group A, there were 14 RVOT abnormality cases (including 7 fPA and 7 PS). No group B fetuses showed RVOT abnormality findings. In group A, later and earlier gestational age at surgery were observed in fPA (25.1 ± 2.8 weeks) and PS groups (17.8 ± 0.9 weeks). All survived PS cases demonstrated progressive pulmonary valve obstruction, not observed in fPA groups. AfNT-proBNP were significantly higher in fPA and PS than in the normal RVOT group (p < 0.05). AfTnT was significantly higher in group A with PS than fPA and normal RVOT groups (p < 0.05). CONCLUSION: Among RVOT abnormality types in group A, amniotic fluid cardiac biomarkers were differently expressed, and clinical features were also differentiated. These findings provide insight into the pathophysiological influence on RVOT in MC twins. CLINICAL TRIAL REGISTRATION: This study was registered with the Japanese Clinical Trial Registry "UMIN-CTR" (http://www.umin.ac.jp/ctr/index-j.htm; trial ID numbers UMIN000024486 and 000037702).

Biochemical effects of intraoperative cell salvage and autotransfusion during cesarean section: A prospective pilot study.

AIM: Intraoperative cell salvage and autotransfusion (ICSA) is a useful technique for women undergoing cesarean sections who are predicted to experience significant bleeding. This method can reduce allogeneic transfusions as well as its associated risks and costs. Amniotic fluid embolism (AFE) is an abnormal maternal response to ICSA similar to the classic systemic inflammatory response syndrome, but its mechanism is not well understood. This study was conducted to investigate the biochemical aspects of AFE. METHODS: A prospective case-controlled pilot study was conducted in a general perinatal hospital in Japan. ICSA was performed using a two-step retransfusion process. Blood samples were collected presurgery, immediately postsurgery, and 24 h after surgery. Changes in sialyl Tn antigen (STN), complement C3 and C4, fibrinogen, and fibrin degradation product and D-dimer, C1 esterase inhibitor, and interleukin-8 (all considered AFE-related markers) activities were compared between patients who underwent cesarean sections with ICSA (ICSA group) versus without ICSA (control group). RESULTS: Fibrinogen levels were significantly lower in the ICSA group than in the control group before surgery but not immediately after or 24 h after surgery. D-dimer was significantly higher immediately after surgery but not 24 h later. STN was significantly lower only before surgery. None of the AFE-related markers showed significant differences between the groups after 24 h. No adverse events were observed in the ICSA group. CONCLUSIONS: There is no clinical evidence that ICSA alters the biochemical statuses of AFE-related markers in a manner that could lead to adverse maternal responses.

Prenatal evaluation of functional pulmonary hypoplasia via fetal magnetic resonance imaging.

OBJECTIVE: The purpose of this study was to retrospectively examine the use of lung-to-liver signal intensity ratio (LLSIR) on T2-weighted images to predict functional pulmonary hypoplasia. METHODS: The subjects of this study were pregnant women who underwent magnetic resonance imaging (MRI). Patients who required nitric oxide inhalation and those who died from respiratory disorders were classified as having functional pulmonary hypoplasia (FPH). All other cases were presented as the control group. We retrospectively analyzed MRI and perinatal data. LLSIR was defined as the ratio of lung signal intensity to liver signal intensity. We examined the relationship between LLSIR and gestational age, compared the LLSIRs in the two groups, and calculated the best cut-off value of the LLSIR to predict FPH. RESULTS: One hundred and ninety-one patients were eligible for this study, and 12 cases were classified as having FPH. In the control group, LLSIR increased with age (r = 0.383, p < 0.001). We used the observed/expected LLSIR (o/e LLSIR), which was the ratio of obtained LLSIR to expected LLSIR calculated by the regression line to correct the effect of gestational age. In the FHP group, o/e LLSIR was significantly lower than in the control group (p < 0.001). A receiver operating characteristic curve analysis showed that cases with o/e LLSIR above 0.85 were less likely to cause FPH. CONCLUSIONS: Low o/e LLSIR might reflect the histological characteristics of hypoplastic lung structures. O/e LLSIR seems to be a useful MRI parameter for screening FPH.

Outcomes of fetoscopic laser surgery for twin-to-twin transfusion syndrome between 26 and 27 weeks of gestation in Japan.

AIM: The purpose of this study was to investigate the outcomes of fetoscopic laser photocoagulation (FLP) for twin-to-twin transfusion syndrome (TTTS) in Japan. METHODS: The retrospective cohort study (2012-2018) was conducted in monochorionic twin pregnancies that underwent FLP for TTTS between 26 and 27 weeks from 2012 to 2018. The perioperative data, maternal complications, gestational age (GA) at delivery, neonatal complications, and survival of infants at 28 days of age were analyzed. At term-equivalent age, severe neurological complications were identified by imaging study. RESULTS: Of 644 patients, 28 (4.3%) underwent FLP between 26 and 27 weeks, and 26 were analyzed. FLP procedures were technically successful in all cases. There were no cases of major maternal complications after surgery. Preterm rupture of membranes occurred in 34.6% of cases, and the mean GA at delivery was 33.2 ± 3.1 weeks. The survival of both twins was found in 23 (88.4%) cases, and the perinatal survival rate of at least one twin at 28 days of age was 100%. Severe neurological complications were found in six (12.2%) cases out of 49. CONCLUSIONS: FLP for TTTS between 26 and 27 weeks provided a good prognosis and caused no major maternal complications. However, severe neurological findings were found in 12% of infants.

Prediction of Twin-to-Twin Transfusion Syndrome Using Characteristic Waveforms of Ductus Venosus in Recipient Twins.

We aimed to investigate whether the alterations of time intervals and velocity-time integrals (VTIs) of ductus venosus (DV) Doppler flow could predict evolving twin-to-twin transfusion syndrome (TTTS) in monochorionic diamniotic (MD) twin pregnancies in the second trimester. DV Doppler waveforms of MD twin pregnancies were retrospectively analyzed. Time intervals and VTIs of the accelerating phase of S-wave (S1 and VTI-1), decelerating phase of S-wave (S2 and VTI-2) and phase of D-wave (D and VTI-diast) were measured in the recipient twins of TTTS and the larger twins of uncomplicated MD twins. Each parameter was normalized to total time intervals and VTIs. DV parameters of prerecipient twins in pre-TTTS conditions were analyzed. The pre-TTTS condition was defined as the condition within 2 weeks before when TTTS cases fulfilled the criteria. Both recipient twins in TTTS cases and prerecipient twins in pre-TTTS condition showed significantly shorter S1, longer S2, shorter D, smaller VTI-1, larger VTI-2 and smaller VTI-diast than did the larger twins in uncomplicated MD twins (p < .05). Receiver-operating characteristic curve analysis showed that VTI-2 had better performance, and VTI-2 >45.5% had 87.0% sensitivity, 90.9% specificity, 81.0% positive predictive value and 93.0% negative predictive value for detecting prerecipient twins. Recipient twins complicated with TTTS have characteristic alterations in time intervals and VTIs of DV Doppler flow, which is present even before fulfilling the TTTS criteria. Furthermore, VTI-2 >45.5% is a possible predictive parameter for TTTS in the second trimester.

Assessment of fetal cardiac function with echocardiography.

The circulatory physiology of fetuses differs from that of neonates. The concept of biventricular combined cardiac output is necessary to understand and assess the fetal cardiac function. Fetal cardiac function has been estimated using echocardiographic methods such as M-mode, B-mode and pulsed wave Doppler. In addition, recent studies have reported the utility of tissue Doppler imaging in fetal echocardiography. However, parameters for fetal cardiac function remain to be established. Recently, we developed two novel techniques for assessing fetal cardiac function: an automatic fractional shortening method and E/e' determination using the dual-gate Doppler method. These two techniques are expected to be reliable and useful for assessing the fetal status in various pathological conditions.

Asymmetrical Hemodynamic Influence of Twin-Twin Transfusion Syndrome on Fetal E/e' by the Dual Gate Doppler Method in Recipient Twins.

OBJECTIVES: To assess the hemodynamic influence of twin-twin transfusion syndrome (TTTS) on diastolic function, using left ventricle (LV) and right ventricle (RV) E/e' measured in the same cardiac cycle using the dual-gate Doppler (DD) method. METHODS: This study included 56 monochorionic twin pregnancies that underwent fetoscopic laser surgery (FLS) for TTTS in 2015-2018. E/e' by the DD method was measured 24 h before and 4-7 days after FLS. RESULTS: Recipients showed higher LV-E/e' Z score in stage I-, II-, and III-recipients (IIIr) and higher RV-E/e' Z score in stage III-donors and IIIr than donors (p < 0.05). After FLS, LV-E/e' Z score of recipients significantly decreased due to LV-E velocity Z score decrease (p < 0.05). RV-E/e' Z score after FLS significantly decreased due to RV-e' velocity Z score increase in recipients (p < 0.05). CONCLUSIONS: E/e' by the DD method helped assess cardiac changes of recipients. LV-E/e' could assess early hemodynamic changes by TTTS, and RV-E/e' can assess later influence on cardiac diastolic function. Furthermore, in recipient twins, the decrease in LV-E/e' after FLS might reflect the improvement of volume overload and the decrease in RV-E/e' might reflect the improvement of diastolic relaxation function in the RV.

Successful use of fetoscopic laser surgery as treatment for a monochorionic-triamniotic triplet pregnancy complicated by twin-reversed arterial perfusion sequence and severe selective fetal growth restriction: A case report.

Monochorionic triplet pregnancy is a rare condition, and twin-reversed arterial perfusion (TRAP) sequence and severe selective fetal growth restriction (FGR) are associated with high perinatal morbidity and mortality rates. We report a case of TRAP sequence and selective FGR typeIIconcurrently complicating a monochorionic triplet pregnancy. Fetoscopic laser surgery (FLS) was performed at 16 + 1 weeks of gestation and was technically successful. Inter-fetus placental anastomoses were coagulated. The pregnancy continued until 28 + 4 weeks of gestation, when the patient presented with preterm rupture of membranes and preterm labor. Two live female newborns were delivered by a cesarean section, and their postnatal course of the neonates was uneventful and in accordance with their gestational age at birth. To our knowledge, this is the first case report of FLS resulting in favorable outcomes for a monochorionic triplet pregnancy concurrently complicated with TRAP sequence and selective FGR type II.

Survival Rate without Brain Abnormalities on Postnatal Ultrasonography among Monochorionic Twins after Fetoscopic Laser Photocoagulation for Selective Intrauterine Growth Restriction with Concomitant Oligohydramnios.

INTRODUCTION: We aimed to clarify the survival rate without brain abnormalities (BA) after fetoscopic laser photoco-agulation (FLP) for monochorionic diamniotic twin gestations (MCDA) with selective intrauterine growth restriction (sIUGR) accompanied by abnormal umbilical artery (UA) Doppler waveforms and isolated oligohydramnios in the sIUGR twin. MATERIALS AND METHODS: This retrospective study included 52 cases that underwent FLP. The main outcome was survival rate without BA of the twins at age 28 days. BA was defined as severe intraventricular hemorrhage and periventricular leukomalacia on postnatal ultrasonography. RESULTS: Median gestational age at FLP was 20 (16-24) weeks. Ten cases were classified as type III based on Doppler for the UA. For all cases, including 20 cases of anterior placenta, FLP was completed without major intraoperative complications. Amnioinfusion was required in 49 cases for better fetoscopic visualization. Fetal loss occurred in 29 sIUGR twins and two larger twins, whereas one larger twin experienced neonatal death. Survival rates without BA were 44% (n = 23) for sIUGR twins and 94% (n = 49) for the larger twins. DISCUSSION: FLP for MCDA with sIUGR presenting with oligohydramnios in the sIUGR twin might be considered a prenatal treatment option.

Utility of fetal anteroposterior to transverse cerebellar diameter ratio to exclude cerebellar hypoplasia in trisomy 18.

AIM: This study was aimed to determine reference ranges for fetal cerebellar hemisphere biometry, including the transverse cerebellar diameter (TCD), anteroposterior cerebellar diameter (APCD) and APCD/TCD ratio in normal fetuses. In addition, we investigated which parameter would be useful for cerebellar hypoplasia in trisomy 18. METHODS: This retrospective study included 340 normal singleton pregnancies and 15 cases of trisomy 18, in all of which fetal cerebellar biometry was performed between 14 and 40 weeks of gestational age (GA). The TCD, APCD and APCD/TCD ratio were assessed ultrasonographically. RESULTS: In normal fetuses, the TCD (rs = 0.876, P < 0.001) and APCD (rs = 0.791, P < 0.001) were strongly correlated with GA. However, the APCD/TCD ratio was not correlated with GA (rs = 0.058, P = 0.289), with median values of 0.52. Low TCD, APCD and APCD/TCD ratio values were detected in 53%, 100% and 100% of trisomy 18 cases, respectively. The median APCD/TCD ratio for trisomy 18 was 0.39 (range, 0.30-0.43), which was significantly lower than that of normal fetuses (P < 0.001). A cut-off APCD/TCD ratio of 0.44 served as a good predictor for trisomy 18 (sensitivity 100%, specificity 95.3% and negative predictive value 100%). CONCLUSION: This study shows that TCD and APCD are correlated with GA, while the APCD/TCD ratio is a fixed value throughout gestation. Using the APCD/TCD ratio to assess cerebellar hypoplasia in trisomy 18 is useful because it does not require the individual evaluation of the TCD and APCD.

Chorioamniotic Membrane Separation after Fetoscopic Laser Photocoagulation.

INTRODUCTION: This study aimed to investigate the risk factors, incidence, and influence on the perinatal outcome of chorioamniotic membrane separation (CMS) after fetoscopic laser photocoagulation (FLP). MATERIAL AND METHODS: This retrospective study included 312 women who underwent FLP for twin-to-twin transfusion syndrome (TTTS). Clinical records were used to review obstetrical examinations, complications, operative data, ultrasonographic findings, and perinatal and neonatal follow-up data in all patients. RESULTS: A total of 260 cases of TTTS were analyzed. The incidence of CMS was 12.7% (33 cases). The only independent risk factor of CMS was performing FLP before 20 weeks of gestational age (GA) (odds ratio = 3.38 [1.44-7.93], p = 0.005). Concerning perinatal outcome, CMS was only related with increased risk of premature rupture of membranes (PROM) before 32 weeks (33.3 vs. 13.9%, p = 0.005), with no differences in GA at delivery and survival rate. DISCUSSION: In our cohort, the incidence of CMS after FLP was approximately 13%, with surgery before 20 weeks being the only risk factor identified. Although in our population CMS did not worsen perinatal outcome in terms of preterm delivery or survival, the preterm PROM rate was increased and this should be considered for the patients' management.

Experience of fetoscopic laser photocoagulation and cord transection for twin-reversed arterial perfusion sequence.

AIM: The purpose of this study was to evaluate the usefulness of fetoscopic laser photocoagulation of placental communicating vessels or umbilical cord for twin-reversed arterial perfusion (TRAP) sequence. MATERIAL AND METHODS: We report a retrospective case series of all cases of TRAP sequence identified from 2006 to 2014 at out institutions. Fetoscopic laser photocoagulation of placental arterioarterial and venovenous anastomoses was performed in diamniotic twins, and in cases of monoamniotic twins we performed laser photocoagulation and transection of the umbilical cord of the acardiac twin to prevent cord entanglement. Pregnancy and perinatal outcomes were estimated. RESULTS: Ten cases were included in the study. The median gestational age at procedure was 21.3 weeks (range, 16.7-27.3 weeks). All cases completed the procedure. Two cases were treated with laser photocoagulation and transection of the umbilical cord of the acardiac twin. No major immediate complications were noted. Preterm rupture of membranes occurred in four cases (40%). One case resulted in miscarriage. The other fetuses were delivered alive. Median gestational age at delivery was 35.4 weeks (range, 25.6-42.0 weeks). Median interval of treatment to delivery was 85 days (range, 43-153 days). Five out four infants were delivered preterm. The overall neonatal survival was 9/10. CONCLUSION: This case series demonstrated favorable outcome, and fetoscopic laser photocoagulation seems to be a useful treatment for TRAP sequence. In particular, transection of the umbilical cord is effective to prevent cord entanglement of monoamniotic twins.

Ratio of fetal anteroposterior to transverse cerebellar diameter for detection of the cerebellar hypoplasia in the second trimester and comparison with trisomy 18.

AIM: Cerebellar hypoplasia, particularly, trisomy 18, represents a chromosomal abnormality. However, morphological assessment of the fetal cerebellum is yet to be established. The purpose of this study was to produce reference values for the fetal transverse cerebellar diameter (TCD), anteroposterior cerebellar diameter (APCD) and the ratio of APCD to TCD (APCD/TCD ratio) in normal fetuses, compared with cases of trisomy 18. METHODS: This retrospective study included 266 normal singleton pregnancies resulting in term delivery at our institution from 2012-2013. Patients had received ultrasound examinations in the second trimester. TCD and APCD measurements were performed and then APCD/TCD ratio was calculated. Consequently, three cases of trisomy 18 were compared with reference values. RESULTS: Gestational age correlated with TCD (rs = 0.766, P < 0.0001) and APCD (rs = 0.61, P < 0.0001), but not with APCD/TCD ratio (rs = 0.070, P = 0.252). The median APCD/TCD ratio was 0.52 and the standard deviation was 0.05. In cases of trisomy 18, all TCD measurements were located within normal ranges. In contrast, both the APCD and APCD/ TCD ratio displayed lower values than that of normal fetuses. CONCLUSIONS: This study showed that not only TCD but also APCD correlated with gestational age, and APCD/TCD ratio indicated a fixed value (almost 0.5) in normal fetuses. Furthermore, APCD and APCD/TCD ratio were deemed useful indicators for cerebellar hypoplasia. In particular, the APCD/TCD ratio proved more convenient, without requiring individual evaluation of TCD and APCD.

The iPREFACE score is useful for predicting fetal acidemia: A retrospective cohort study of 113 patients who underwent emergency cesarean section for non-reassuring fetal status during labor.

BACKGROUND: The iPREFACE score may aid in predicting fetal acidemia and neonatal asphyxia in emergency cesarean and vaginal deliveries, which may improve labor management precision in the future. OBJECTIVE: This study aimed to assess the score use of the iPREFACE as an objective indicator of the need for rapid delivery in cases of repeated abnormal waveforms without concurrent indications for immediate medical intervention during labor. STUDY DESIGN: This retrospective cohort study was conducted among term (37+ 0 days to 41+6 days) singleton pregnant women who underwent emergency cesarean delivery owing to a nonreassuring fetal status. The integrated score index to predict fetal acidemia by intrapartum fetal heart rate monitoring-decision of emergency cesarean delivery score, calculated from a 30-minute cardiotocography waveform before the decision to perform emergency cesarean delivery, and the integrated score index to predict fetal acidemia by intrapartum fetal heart rate monitoring-removal of cardiotocography transducer score, calculated from a 30-minute cardiotocography waveform before cardiotocography transducer removal, were employed. The primary outcome was the assessment of the predictive ability of these scores for fetal acidemia, whereas the secondary outcomes were differences in umbilical artery blood gas findings and postnatal outcomes between the 2 groups, divided by the cutoff values of the integrated score index to predict fetal acidemia by intrapartum fetal heart rate monitoring-removal of cardiotocography score. RESULTS: The integrated score index to predict fetal acidemia by intrapartum fetal heart rate monitoring-decision of emergency cesarean delivery and integrated score index to predict fetal acidemia by intrapartum fetal heart rate monitoring-removal of cardiotocography transducer scores demonstrated the capability to predict an umbilical artery blood pH of <7.2. The integrated score index to predict fetal acidemia by intrapartum fetal heart rate monitoring-decision of emergency cesarean delivery and -removal of cardiotocography transducer score, with cutoff values of 37 and 46 points, respectively, exhibited an area under the receiver operating characteristic curve of 0.82 and 0.87, respectively. The integrated score index to predict fetal acidemia by intrapartum fetal heart rate monitoring-removal of cardiotocography transducer group with ≥46 points had higher incidence rates of an umbilical cord artery blood pH of <7.2, <7.1, and <7.0 and neonatal intensive care unit admissions for neonatal asphyxia. CONCLUSION: The integrated score index to predict fetal acidemia by intrapartum fetal heart rate monitoring, derived from cardiotocography during an emergency cesarean delivery, may enable clinicians to predict fetal acidemia in cases of nonreassuring fetal status. Improved prediction of fetal acidemia and facilitation of timely intervention hold promise for enhancing the outcomes of mothers and newborns during childbirth. Prospective studies are warranted to establish precise cutoff values and to validate the clinical application of these scores.

Association of amniotic fluid natriuretic peptide levels with ductus venosus Doppler flow in recipient twins with twin-to-twin transfusion syndrome : DV flow and NT-proBNP in TTTS recipient twins.

PURPOSE: This study examined the relationships between fetal quantitative Doppler parameters and amniotic fluid N-terminal prohormone brain natriuretic peptide (afNT-proBNP) levels as a biomarker of the increased cardiac load in recipient twins with twin-to-twin transfusion syndrome (TTTS). METHODS: This single-center, prospective study included all monochorionic diamniotic (MD) twin pregnancies that were diagnosed with TTTS and underwent fetoscopic laser surgery. Doppler flow was used to measure the pulsatility index (PI) of the umbilical artery (UA), ductus venosus (DV), and middle cerebral artery (MCA) of each recipient and donor twins. The afNT-proBNP levels of recipient twins were examined at the time of surgery. The Spearman or Pearson correlation coefficients were used to assess the relationships between afNT-proBNP levels and Doppler parameters. RESULTS: A total of 150 MD twin pregnancies were included. The afNT-proBNP levels of the recipient twins showed a stronger correlation with the DV-PI (r = 0.637; P < 0.001) of recipient twins than with the UA-PI and MCA-PI of recipient twins. The Doppler parameters of donor twins were scarcely correlated with the afNT-proBNP levels of the recipient twins. CONCLUSION: A positive correlation between the DV-PI and afNT-proBNP levels of recipient twins with TTTS was observed. The recipient twin with an increased DV-PI is expected to be under a high cardiac load; therefore, DV-PI is a useful parameter for assessing increased NT-proBNP levels consecutively and noninvasively. CLINICAL TRIAL REGISTRATION: This study was registered with Japanese Clinical Trial Registry "UMIN-CTR" ( http://www.umin.ac.jp/ctr/index-j.htm ; trial ID numbers UMIN000024486 and 000037702).

Optimal duration of cardiotocography assessment using the iPREFACE score to predict fetal acidemia.

Cardiotocography (CTG) applicability to improve fetal outcomes remains controversial. This study aimed to determine the clinically optimal CTG assessment duration using the integrated score index to predict fetal acidemia by intrapartum fetal heart rate monitoring (iPREFACE score). This single-center, retrospective observational study included 325 normal full-term singleton vaginal deliveries at the Toho University Omori Medical Center, from September 2018 to March 2019. The iPREFACE(10), iPREFACE(30), and iPREFACE(60) scores were calculated at 10, 30, and 60 min immediately before delivery. The primary outcome was fetal acidemia (umbilical artery blood pH < 7.2). The secondary outcome was the correlation between all iPREFACE scores and the umbilical artery blood pH, base excess (BE), and lactate values. Patients without accurate CTG findings or with failure of umbilical artery blood sampling immediately after birth were excluded, leaving 145 patients in the final analysis. Of these, 16, three, and two had umbilical artery blood pH of < 7.2, < 7.1, and < 7.0, respectively. All iPREFACE scores significantly correlated with umbilical artery blood pH, BE, and lactate values. iPREFACE(30) had the highest predictive capacity for fetal acidemia, suggesting that 30 min immediately before delivery may be a useful scoring time in clinical practice.

Tadalafil treatment for fetuses with early-onset growth restriction: a protocol for a multicentre, randomised, placebo-controlled, double-blind phase II trial (TADAFER IIb).

INTRODUCTION: TheTADAlafil treatment for Fetuses with early-onset growth Restriction: multicentrer, randomizsed, phase II trial (TADAFER II) study showed the possibility of prolonging the pregnancy period in cases of early-onset fetal growth restriction; however, it was an open-label study. To establish further evidence for the efficacy of tadalafil in this setting, we planned a multicentre, randomised, placebo-controlled, double-blind trial. METHODS AND ANALYSIS: This trial will be conducted in 180 fetuses with fetal growth restriction enrolled from medical centres in Japan; their mothers will be randomised into three groups: arm A, receiving two times per day placebo; arm B, receiving one time per day 20 mg tadalafil and one time per day placebo and arm C, receiving 20 mg two times per day tadalafil. The primary endpoint is the prolongation of gestational age at birth, defined as days from the first day of the protocol-defined treatment to birth. To minimise bias in terms of fetal baseline conditions and timing of delivery, a fetal indication for delivery as in TADAFER II will be established in this trial. The investigator will evaluate fetal baseline conditions at enrolment and decide the timing of delivery based on this indication. ETHICS AND DISSEMINATION: This study has been approved by Mie University Hospital Clinical Research Review Board on 22 July 2019 (S2018-007). Written informed consent will be obtained from all mothers before recruitment. Our findings will be widely disseminated through peer-reviewed publications. TRIAL REGISTRATION: jRCTs041190065.

Measurement of fetal automated fractional shortening using two-dimensional tracking in multiple centers.

PURPOSE: To establish a normal reference range for automated fractional shortening (Auto FS) in normal singleton fetuses measured at multiple centers. METHODS: This study was conducted from May 2017 to March 2019. It was undertaken on normal singleton fetuses. First, a four-chamber view of the fetal heart was recorded in the B-mode. Then, the region of interest was set on the edge of the ventricular septum and on the edge of the ventricular muscle at a point one-third away from the atrioventricular valve and toward the cardiac apex. Tracking was automatically performed. Values measured in the right ventricle were defined as R-Auto FS, and in the left ventricle as L-Auto FS. Furthermore, combined-Auto FS was defined as the measurement across both ventricles. RESULTS: A total of 442 normal fetuses were assessed. R-Auto FS decreased significantly with gestational age, and L-Auto FS showed a similar tendency (Spearman's correlation analysis: rs = - 0.415 and rs = - 0.252, respectively). Combined-Auto FS showed a similar decline as the gestational age increased (rs = - 0.451). CONCLUSION: In this study, we succeeded in defining a reference Auto FS value not only at one institution but also multiple centers. This study suggests that Auto FS can be used clinically and effectively.