Severity of haemolytic disease of the fetus and newborn in patients with a history of intrauterine transfusions in a previous pregnancy: A nationwide retrospective cohort study.

OBJECTIVE: Pregnant women who received at least one intrauterine transfusion (IUT) for haemolytic disease of the fetus and newborn (HDFN) in the preceding pregnancy are presumed to have a high likelihood of requiring IUTs again, often starting at an earlier gestational age. Our aim was to quantify these risks in a large national cohort. DESIGN: Retrospective cohort study of a nationwide Dutch database. SETTING: The Netherlands. POPULATION: All women treated in The Netherlands with IUTs for Rhesus D (RhD)- or Kell-mediated HDFN between 1999 and 2017 and their follow-up pregnancies were included. Pregnancies with an antigen-negative fetus were excluded. METHODS: Electronic patient files were searched for the number and gestational age of each IUT, and analysed using descriptive statistics and linear regression. MAIN OUTCOME MEASURES: Percentage of women requiring one or more IUTs again in the subsequent pregnancy, and gestational age at first IUT in both pregnancies. RESULTS: Of the 321 women in our study population, 21% (69) had a subsequent ongoing pregnancy at risk. IUTs were administered in 86% (59/69) of cases. In subsequent pregnancies, the median gestational age at first IUT was 3 weeks earlier (interquartile range -6.8 to 0.4) than in the preceding pregnancy. CONCLUSIONS: Our study shows that pregnant women with a history of IUTs in the previous pregnancy are highly likely to require IUTs again, and on average 3 weeks earlier. Clinicians need to be aware of these risks and ensure timely referral, and close surveillance from early pregnancy onwards. Additionally, for women with a history of IUT and their caregivers, this information is essential to enable adequate preconception counselling.

Fetal cardiovascular changes during open and fetoscopic in-utero spina bifida closure.

OBJECTIVE: Fetoscopic closure of spina bifida using heated and humidified carbon dioxide gas (hhCO2) has been associated with lower maternal morbidity compared with open closure. Fetal cardiovascular changes during these surgical interventions are poorly defined. Our objective was to compare fetal bradycardia (defined as fetal heart rate (FHR) < 110 bpm for 10 min) and changes in umbilical artery (UA) Doppler parameters during open vs fetoscopic closure. METHODS: This was a prospective cohort study of 22 open and 46 fetoscopic consecutive in-utero closures conducted between 2019 and 2023. Both cohorts had similar preoperative counseling and clinical management. FHR and UA Doppler velocimetry were obtained systematically during preoperative assessment, every 5 min during the intraoperative period, and during the postoperative assessment. FHR, UA pulsatility index (PI) and UA end-diastolic flow (EDF) were segmented into hourly periods during surgery, and the lowest values were averaged for analysis. Umbilical vein maximum velocity was measured in the fetoscopic cohort. At each timepoint at which FHR was recorded, maternal heart rate and systolic and diastolic blood pressure were measured. RESULTS: Fetal bradycardia occurred in 4/22 (18.2%) cases of open closure and 21/46 (45.7%) cases of fetoscopic closure (P = 0.03). FHR decreased gradually in both cohorts after administration of general anesthesia and decreased further during surgery. FHR was significantly lower during hour 2 of surgery in the fetoscopic-repair cohort compared with the open-repair cohort. The change in FHR from baseline in the final stage of fetal surgery was significantly more pronounced in the fetoscopic-repair cohort compared with the open-repair cohort (mean, -32.4 (95% CI, -35.7 to -29.1) bpm vs -23.5 (95% CI, -28.1 to -18.8) bpm; P = 0.002). Abnormal UA-EDF (defined as absent or reversed EDF) occurred in 3/22 (13.6%) cases in the open-repair cohort and 23/46 (50.0%) cases in the fetoscopic-repair cohort (P = 0.004). There were no differences in UA-EDF or UA-PI between closure techniques at the individual stages of assessment. CONCLUSIONS: We observed a decrease in FHR and abnormalities in UA Doppler parameters during both open and fetoscopic spina bifida closure. Fetal bradycardia was more prominent during fetoscopic closure following hhCO2 insufflation, but FHR recovered after cessation of hhCO2. Changes in FHR and UA Doppler parameters during in-utero spina bifida closure were transient, no cases required emergency delivery and no fetoscopic closure was converted to open closure. These observations should inform algorithms for the perioperative management of fetal bradycardia associated with in-utero spina bifida closure. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.

Elevated middle cerebral artery peak systolic velocity and risk of death in donor twin affected by twin-twin transfusion syndrome but not twin anemia-polycythemia sequence.

OBJECTIVES: To determine the association between elevated (> 1.5 multiples of the median (MoM)) middle cerebral artery (MCA) peak systolic velocity (PSV) and fetal demise of the donor twin in pregnancies complicated by twin-twin transfusion syndrome (TTTS) in the absence of twin anemia-polycythemia sequence (TAPS). Secondary objectives were to evaluate if donor or recipient MCA-PSV is associated with a risk for their corresponding fetal death, and to compare the proportion of donor fetuses with low MCA pulsatility index (PI) among donor twins with high MCA-PSV and those with normal MCA-PSV to evaluate the contribution of blood-flow redistribution to the fetal brain in donor twins with high MCA-PSV. METHODS: This prospective cohort study included TTTS cases that underwent laser surgery between 2011 and 2022 at a single center. TAPS cases were excluded from the study. Multivariable and Poisson regression analysis were performed to explore the association between isolated elevated donor MCA-PSV and fetal demise, adjusted for TTTS stage, selective fetal growth restriction (sFGR) and other confounders. RESULTS: Of 660 TTTS cases, donor MCA-PSV was not recorded in 48 (7.3%) cases. Of the remaining 612 patients, nine (1.5%) were lost to follow-up and 96 TAPS cases were excluded; thus, 507 cases were included in the study. High donor MCA-PSV was seen in 6.5% (33/507) of cases and was an independent risk factor for donor fetal demise (adjusted relative risk (aRR), 4.52 (95% CI, 2.72-7.50)), after adjusting for confounders. Regression analysis restricted to each Quintero TTTS stage demonstrated that high donor MCA-PSV was an independent risk factor for fetal demise of the donor in Quintero Stage II (aRR, 14.21 (95% CI, 1.09-186.2)) and Quintero Stage III (aRR, 3.41 (95% CI, 1.82-6.41)). Donor MCA-PSV in MoM was associated with fetal demise of the donor (area under the receiver-operating-characteristics curve (AUC), 0.69; P < 0.001), but recipient MCA-PSV in MoM was not associated with fetal demise of the recipient (AUC, 0.54; P = 0.44). A higher proportion of donor twins in the group with high MCA-PSV had a low MCA-PI compared to the group with normal MCA-PSV (33.3% vs 15.5%; P = 0.016). CONCLUSIONS: Elevated donor MCA-PSV without TAPS prior to laser surgery for TTTS is associated with a 4-fold increased risk for donor fetal demise, adjusted for sFGR, TTTS stage and other confounders. Doppler evaluation of donor MCA-PSV prior to laser surgery may help stratify TTTS staging to evaluate the risk of donor fetal demise. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.

Fetal and neonatal neuroimaging in twin-twin transfusion syndrome.

OBJECTIVES: To describe the types of brain injury and subsequent neurodevelopmental outcome in fetuses and neonates from pregnancies with twin-twin transfusion syndrome (TTTS). Additionally, to determine risk factors for brain injury and to review the use of neuroimaging modalities in these cases. METHODS: This was a retrospective cohort study of consecutive TTTS pregnancies treated with laser surgery in a single fetal therapy center between January 2010 and January 2020. The primary outcome was the incidence of brain injury, classified into predefined groups. Secondary outcomes included adverse outcome (perinatal mortality or neurodevelopmental impairment), risk factors for brain injury and the number of magnetic resonance imaging (MRI) scans. RESULTS: Cranial ultrasound was performed in all 466 TTTS pregnancies and in 685/749 (91%) liveborn neonates. MRI was performed in 3% of pregnancies and 4% of neonates. Brain injury was diagnosed in 16/935 (2%) fetuses and 37/685 (5%) neonates and all predefined injury groups were represented. Four fetal and four neonatal cases of cerebellar hemorrhage were detected. Among those with brain injury, perinatal mortality occurred in 11/16 (69%) fetuses and 8/37 (22%) neonates. Follow-up was available for 29/34 (85%) long-term survivors with brain injury and the mean age at follow-up was 46 months. Neurodevelopmental impairment was present in 9/29 (31%) survivors with brain injury. Adverse outcome occurred in 28/53 (53%) TTTS individuals with brain injury. The risk of brain injury was increased after recurrent TTTS/post-laser twin anemia-polycythemia sequence (TAPS) (odds ratio (OR), 3.095 (95% CI, 1.581-6.059); P = 0.001) and lower gestational age at birth (OR per 1-week decrease in gestational age, 1.381 (95% CI, 1.238-1.541); P < 0.001). CONCLUSIONS: Based on dedicated neurosonography and limited use of MRI, brain injury was diagnosed in 2% of fetuses and 5% of neonates with TTTS. Adverse outcome was seen in over half of cases with brain injury. Brain injury was related to recurrent TTTS/post-laser TAPS and a lower gestational age at birth. © 2024 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

The Conundrum of Mechanics Versus Genetics in Congenital Hydrocephalus and Its Implications for Fetal Therapy Approaches: A Scoping Review.

Recent advances in gene therapy, particularly for single-gene disorders (SGDs), have led to significant progress in developing innovative precision medicine approaches that hold promise for treating conditions such as primary hydrocephalus (CH), which is characterized by increased cerebrospinal fluid (CSF) volumes and cerebral ventricular dilation as a result of impaired brain development, often due to genetic causes. CH is a significant contributor to childhood morbidity and mortality and a driver of healthcare costs. In many cases, prenatal ultrasound can readily identify ventriculomegaly as early as 14-20 weeks of gestation, with severe cases showing poor neurodevelopmental outcomes. Postnatal surgical approaches, such as ventriculoperitoneal shunts, do not address the underlying genetic causes, have high complication rates, and result in a marginal improvement of neurocognitive deficits. Prenatal somatic cell gene therapy (PSCGT) promises a novel approach to conditions such as CH by targeting genetic mutations in utero, potentially improving long-term outcomes. To better understand the pathophysiology, genetic basis, and molecular pathomechanisms of CH, we conducted a scoping review of the literature that identified over 160 published genes linked to CH. Mutations in L1CAM, TRIM71, MPDZ, and CCDC88C play a critical role in neural stem cell development, subventricular zone architecture, and the maintenance of the neural stem cell niche, driving the development of CH. Early prenatal interventions targeting these genes could curb the development of the expected CH phenotype, improve neurodevelopmental outcomes, and possibly limit the need for surgical approaches. However, further research is needed to establish robust genotype-phenotype correlations and develop safe and effective PSCGT strategies for CH.

Impact of cannula diameter on pregnancy outcomes after minimally invasive fetal laser surgery in the treatment of twin-to-twin transfusion syndrome: A systematic review and meta-analysis.

INTRODUCTION: Preterm prelabor rupture of membranes (PPROM) remains a major complication of fetal laser surgery in the treatment of twin-to-twin transfusion syndrome (TTTS). The aim of the study was to determine the impact of cannula size on pregnancy outcomes, with a particular focus on PPROM. MATERIAL AND METHODS: The protocol was developed and registered in the PROSPERO database under registration number CRD42022333630. The PubMed, Web of Science, and EMBASE databases were searched electronically on May 18, 2022, and updated on March 2, 2023, utilizing a combination of the relevant MeSH terms, keywords, and word variants for "TTTS" and "laser". Randomized controlled trials, prospective and retrospective cohorts, case-control studies, and case reports/series with more than five participants were considered eligible for inclusion. Studies reporting the cannula diameter and PPROM rate after laser surgery in the treatment of monochorionic pregnancies affected by TTTS between 16- and 26 weeks' gestation were included. Data was extracted independently, and when appropriate, a random-effects meta-analysis was undertaken to calculate pooled estimates and their confidence intervals. Heterogeneity in the effect estimates of the individual studies was calculated using the I2 statistic. The primary outcome was PPROM rate. Secondary outcomes were survival rate, preterm birth, and incomplete surgery. The quality of the included studies was assessed using a modified quality in prognosis study tool. RESULTS: We included a total of 22 studies, consisting of 3426 patients. Only one study was scored as low quality, seven as moderate quality, and the remaining 14 as high quality. The mean PPROM rate after laser surgery treating TTTS was 22.9%, ranging from 11.6% for 9 French (Fr) to 54.0% for 12 Fr. Subsequent meta-regression for the clinically relevant PPROM rate before 34 weeks of gestation, showed increased PPROM rates for increased cannula size (p-value 0.01). CONCLUSIONS: This systematic review confirmed PPROM as a frequent complication of fetal laser surgery, with a mean PPROM rate of 22.9%. A larger cannula diameter relates to a significant higher PPROM risk for PPROM before 34 weeks gestation. Hence, the ideal balance between optimal visualization requiring larger port diameters and shorter operation time and more complete procedures that benefit from larger diameters is crucial to reduce iatrogenic PPROM rates.

Advancement of 3D printing technology for the development of a training model in US-guided vesicoamniotic shunting for early LUTO therapy.

INTRODUCTION: Prenatal lower urinary tract obstruction (LUTO) is a rare and challenging condition with potential severe morbidity and mortality. Prenatal shunting methods, specifically vesicoamniotic shunting (VAS) and fetal cystoscopy, aim to manage this condition. However, comprehensive education and training are hindered by the rarity of LUTO. To address this gap, we present a low-cost 3D-printed ultrasound training model for VAS in LUTO fetuses. The aim of the study was to evaluate ultrasound and haptic fidelity of the model. MATERIAL AND METHODS: Ultrasound images of three LUTO fetuses at 12-14 weeks were utilized to create detailed 3D-printed models. Fusion360TM software generated stereo-lithography files, and the Formlabs Form3® printer, using Flexible 80A resin, produced the models. A simulation box mimicking uterine conditions and fetal anatomy was developed for testing. Ultrasound assessments determined model accuracy, and expert evaluations gauged fidelity for VAS placement. RESULTS: The 3D-printed model accurately replicated LUTO fetal anatomy, demonstrating structural integrity and realistic sonographic and haptic feedback during 20 punctures. Macroscopic visualization confirmed the model's durability and authenticity. DISCUSSION: This innovative 3D-printed model addresses the scarcity of LUTO cases and the lack of realistic training tools. Simulation models enhance skills, providing a controlled learning environment that bridges theoretical knowledge and clinical application, potentially improving patient outcomes. CONCLUSIONS: The 3D-printed training model for VAS in LUTO represents a significant advancement in surgical education, offering realistic anatomical simulation and tactile feedback. Future studies should assess its effectiveness in enhancing surgical skills and impacting patient outcomes in clinical practice.

Hepatic arterial buffer response: activation in donor fetuses and the effect of laser ablation of intertwin anastomosis.

OBJECTIVES: Hepatic arterial buffer response (HABR) is an important defence mechanism for maintaining liver blood flow. It is suspected that HABR is active in monochorionic diamniotic twins (MCDA) with twin-to-twin transfusion syndrome (TTTS) where donor compensates a setting of volume depletion and the recipient an overload. The present study investigates whether in TTTS, HABR is active in donor and/or recipient individually and try to determine if the activation of HABR is a direct response to TTTS. METHODS: Hepatic artery (HA) peak systolic velocity (PSV) was measured in normal MCDA fetuses and TTTS. Correlation with relevant fetal Dopplers and characteristics were determined. Z-scores for HA-PSV (HAV-Z) were calculated and its association with TTTS in donors and recipients were determined as well as changes in HAV-Z after laser treatment. RESULTS: In this study 118 MCDA were included, 61.9 % normal and 38.1 % TTTS. Of the TTTS 22 required laser treatment. A total of 382 scans were performed in normal group and 155 in TTTS. Our data demonstrates that in donors HAV-Z was 2.4 Z-scores higher compared to normal fetuses (ß=2.429 95 % CI 1.887, 2.971; p<0.001) and after laser treatment HAV-Z reduced (ß=-1.829 95 % CI -2.593, -1.064; p<0.001). There was no significant difference between recipients and normal (ß=-0.092 95 % CI -0.633, 0.449; p=0.738). CONCLUSIONS: HABR is active in TTTS, promoting an increased hepatic blood flow in donors. The activation is direct response to TTTS as shown by the reduction in HAV-Z after laser. This finding provides important insights into the pathophysiology of TTTS.

Prenatal Management and Perinatal Outcome in a Large Series of Hydrops Fetalis.

INTRODUCTION: Nonimmune hydrops fetalis (NIHF) is the most frequent etiology of hydrops fetalis (HF), accounting for around 95% of cases. It associates high perinatal mortality and morbidity rates. The aim of the study was, first, to investigate etiology, prenatal management, and perinatal outcome in a large single-center series of HF; second, to identify prenatal prognostic factors with impact on perinatal outcome. MATERIALS AND METHODS: Observational retrospective study of 80 HF diagnosed or referred to a single tertiary center between 2012 and 2021. Clinical characteristics, etiology, prenatal management, and perinatal outcome were recorded. Adverse perinatal outcome was defined as intrauterine fetal death (IUFD), early neonatal death (first 7 days of life) and late neonatal death (between 7 and 28 days). RESULTS: Seventy-six of the 80 cases (95%) were NIHF, main etiology being genetic disorders (28/76; 36.8%). A total of 26 women (32.5%) opted for termination of pregnancy, all of them in the NIHF group. IUFD occurred in 24 of 54 patients (44.4%) who decided to continue the pregnancy. Intrauterine treatment was performed in 29 cases (53.7%). There were 30 newborns (55.6%). Adverse perinatal outcome rate was 53.7% (29/54), significantly higher in those diagnosed <20 weeks of gestation (82.4% < 20 weeks vs. 40.5% ≥ 20 weeks; p = 0.004). Survival rate was higher when fetal therapy was performed compared to the expectantly managed group (58.6% vs. 32%; p = 0.05). Intrauterine blood transfusion and thoraco-amniotic shunt were the procedures that achieved the highest survival rates (88.9% and 100%, respectively, p = 0.003). CONCLUSION: NIHF represented 95% of HF with genetic disorders as the main etiology. Most of them were diagnosed before 20 weeks of gestation, with worse prognosis than cases detected later in gestation. Rates of TOP, IUFD, and early neonatal death were higher in NIHF. Intrauterine therapy, when indicated, improved the perinatal outcome.

Comparison of Serial Amnioinfusion Strategies for Isolated Early-Onset Fetal Renal Anhydramnios.

INTRODUCTION: The optimal protocol for serial amnioinfusions to maintain amniotic fluid in pregnancies with early-onset fetal renal anhydramnios before 22 weeks is not known. We compared the performance of two different approaches. METHODS: A secondary analysis was conducted of serial amnioinfusions performed by a single center during the external pilot and feasibility phases of the Renal Anhydramnios Fetal Therapy (RAFT) trial. During the external pilot, higher amnioinfusion volumes were given less frequently; in the feasibility study, smaller volume amnioinfusions were administered more frequently. Procedural details, complications, and obstetric outcomes were compared between the two groups using Pearson's χ2 or Fisher's exact tests for categorical variables and Student's t tests or Wilcoxon rank-sum tests for continuous variables. The adjusted association between procedural details and chorioamniotic separation was obtained through a multivariate repeated measure logistic regression model. RESULTS: Eleven participants underwent 159 amnioinfusions (external pilot: 3 patients, 21 amnioinfusions; feasibility: 8 patients, 138 amnioinfusions). External pilot participants had fewer amnioinfusions (7 vs. 19.5 in the feasibility group, p = 0.04), larger amnioinfusion volume (750 vs. 500 mL, p < 0.01), and longer interval between amnioinfusions (6 [4-7] vs. 4 [3-5] days, p < 0.01). In the external pilot, chorioamniotic separation was more common (28.6% vs. 5.8%, p < 0.01), preterm prelabor rupture of membranes (PPROM) occurred sooner after amnioinfusion initiation (28 ± 21.5 vs. 75.6 ± 24.1 days, p = 0.03), and duration of maintained amniotic fluid between first and last amnioinfusion was shorter (38 ± 17.3 vs. 71 ± 19 days, p = 0.03), compared to the feasibility group. While delivery gestational age was similar (35.1 ± 1.7 vs. 33.8 ± 1.5 weeks, p = 0.21), feasibility participants maintained amniotic fluid longer. CONCLUSION: Small volume serial amnioinfusions performed more frequently maintain normal amniotic fluid volume longer because of delayed occurrence of PPROM.

Immunomodulation for early-onset haemolytic disease of the fetus/newborn: Can we delay the need for intrauterine transfusions?

When cases of severe fetal anaemia due to maternal red-cell alloimmunization present in the early second trimester, standard treatment with intrauterine transfusion often results in fetal loss. The report by Vlachodimitropoulou et al. offers new insight into the use of maternal intravenous immune globulin to delay the need for intrauterine transfusion. Performing these procedures at a later gestational age increases the likelihood of technical success and subsequent perinatal survival. Commentary on: Vlachodimitropoulou et al. Intravenous immune globulin in the management of severe early onset of red cell alloimmunization. Br J Haematol 2023; 200:97-103.

Hematogenous Routing of Exogenous Messenger RNA Delivered Into the Amniotic Fluid.

INTRODUCTION: Therapies based on exogenous messenger RNA (mRNA) administration have emerged as a powerful novel strategy for the actual or potential treatment of an assortment of diseases, including congenital surgical pathologies. We sought to determine whether the minimally invasive transamniotic route could be an alternative for prenatal mRNA delivery. METHODS: Pregnant Sprague-Dawley dams underwent laparotomy followed by volume-matched intra-amniotic injections in all their fetuses (n = 120) of either a suspension of a custom firefly luciferase mRNA encapsulated by a lipid- and synthetic cationic polymer-based composite, or of a suspension of the same encapsulation components without mRNA, on gestational day 17 (E17; term = E21-22). On E18, E19, E20, and E21, samples from 14 fetal anatomical sites and maternal serum were procured for the screening of mRNA incorporation by host cells by measurement of luciferase activity via microplate luminometry. Statistical analysis was by Mann-Whitney U-test, including Bonferroni-adjustment. RESULTS: Overall survival was 87.5% (105/120). Controlled by the encapsulating composite without mRNA, luciferase activity was detected in the animals that received encapsulated mRNA in the following fetal annexes: amniotic fluid, amnion, chorion, umbilical cord, and placenta (P = 0.033 to <0.001), as well as in the following fetal sites: liver, stomach, intestines, and lungs (P = 0.043-0.002). CONCLUSIONS: Packaged exogenous mRNA can be incorporated by the fetus at least at select anatomical sites after simple intra-amniotic administration in a rodent model. The pattern and chronology of mRNA incorporation are compatible with transplacental hematogenous routing, as well as with fetal swallowing/aspiration. Further study of transamniotic mRNA administration is warranted.

Management of large placental chorioangioma: two-port laser approach for fetal intervention.

OBJECTIVES: There is a paucity of literature providing evidence-based guidelines for the management of large placental chorioangioma (≥ 4 cm in diameter). The objectives of this study were to compare outcomes between patients managed expectantly and those undergoing in-utero intervention and to describe the different in-utero techniques used for cessation of blood flow to the tumor and the associated outcome. METHODS: This was a retrospective cohort study of 34 patients referred for the management of large placental chorioangioma in a single center between January 2011 and December 2022, who were managed expectantly or underwent in-utero intervention. In-utero intervention was performed when the fetus developed any signs of impending compromise, including high combined cardiac output (CCO), worsening polyhydramnios or abnormal fetal Doppler velocimetry findings. Interventions included radiofrequency ablation (RFA), interstitial laser ablation (ILA) and single-port or two-port fetoscopic laser photocoagulation (FLP). Treatment selection was dependent on the proximity of the tumor to the umbilical cord insertion (UCI) and placental location. The two-port technique was performed in patients with a chorioangioma with large feeding vessels (≥ 3 mm) located in the posterior placenta, in which one port was used for occlusion using bipolar forceps and the other port was used for laser photocoagulation of the feeding vessels downstream. The single-port technique was used for chorioangioma with small feeding vessels (< 3 mm) located in the posterior placenta. ILA or RFA was performed in cases with an anterior placenta. Supportive treatments, including amnioreduction and intrauterine transfusion (IUT), were performed for worsening polyhydramnios and suspected fetal anemia based on middle cerebral artery Doppler flow studies, respectively. Comparative statistical analysis between cases undergoing expectant management vs in-utero intervention was performed. Descriptive details were provided for patients who underwent in-utero intervention. RESULTS: Thirty-four cases of large chorioangioma were evaluated, of which 25 (73.5%) were managed expectantly and nine (26.5%) underwent intervention. The frequency of polyhydramnios was significantly higher in the intervention group compared with the expectant-management group (66.7% vs 8.0%, P < 0.001). The live-birth rate among expectantly managed cases with large chorioangioma was significantly higher compared with that in cases that underwent in-utero intervention (96.0% vs 62.5%, P = 0.01). In the intervention group, preoperative CCO was elevated in all cases with available information and preoperative hydrops was present in 33.3% (3/9) of cases. One patient experienced fetal demise following IUT prior to planned FLP. Among the remaining eight patients, four underwent two-port FLP, two underwent single-port FLP, one underwent ILA and one underwent both ILA and RFA. All three cases in which hydrops was present at the time of intervention resulted in fetal demise. CONCLUSIONS: In-utero interventions aimed at cessation of blood flow in the feeding vessels are a therapeutic option for the management of cases with large chorioangioma. The two-port percutaneous technique appears to improve the efficiency of FLP when a large chorioangioma with large feeding vessels is located in the posterior placenta. We propose that in-utero interventions for large chorioangioma should be initiated prior to the development of fetal hydrops. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Presurgery motor level assessment for prediction of motor level at birth in fetuses undergoing prenatal repair of open spina bifida: time to abandon anatomical level in counseling.

OBJECTIVES: First, to investigate the correlation between prenatal presurgery anatomical and motor levels of the lesion with motor level at birth in cases undergoing prenatal repair of open spina bifida and, second, to identify factors leading to a loss of two or more motor levels between the presurgery and postnatal assessments. METHODS: This was an observational study of singleton pregnancies undergoing prenatal repair of open spina bifida, conducted between March 2011 and May 2022. All fetuses underwent an ultrasound assessment at 20-24 weeks of gestation to determine the motor and anatomical levels of the lesion before surgery. The anatomical level of the lesion was defined as the highest open posterior vertebral arch. The motor level was determined by systematic observation of the lower limb movements and was defined as the most distal active muscle present. Prenatal repair was performed at 23-26 weeks. At birth, motor level was assessed by a rehabilitation specialist by physical examination. Cases of intrauterine death or termination of pregnancy and those delivered at other sites were excluded from the neonatal assessment. The agreement between presurgery motor level and motor level at birth, and between presurgery anatomical level and motor level at birth, was assessed using the weighted kappa index (wκ). Logistic regression analysis was used to assess factors leading to a loss of two or more motor levels between the presurgery and postnatal assessments. RESULTS: Presurgery motor and anatomical levels were assessed in 61 fetuses at a median gestational age of 22.7 (interquartile range (IQR), 21.6-24.4) weeks. Prenatal repair was performed at a median gestational age of 24.6 (IQR, 23.7-25.7) weeks. Motor level at birth was assessed in 52 neonates after exclusion of nine fetuses due to loss to follow-up or fetal loss. There was moderate agreement between presurgery motor level and motor level at birth (wκ = 0.42; 95% CI, 0.21-0.63), with a median difference of 0 (IQR, -2 to 9) levels. Factors leading to a loss of two or more motor levels between the presurgery ultrasound assessment and postnatal examination were higher presurgery anatomical level (odds ratio (OR), 0.59 (95% CI, 0.35-0.98); P = 0.04) and larger difference between the anatomical and motor levels before surgery (OR, 1.85 (95% CI, 1.12-3.06); P = 0.017). None of the other ultrasound, surgery-related or neonatal variables assessed was associated significantly with a loss of two or more motor levels. There was slight agreement between the presurgery anatomical level of the lesion and motor level at birth (wκ = 0.07; 95% CI, -0.02 to 0.15). CONCLUSIONS: There is moderate agreement between fetal motor level of the lesion before prenatal repair of open spina bifida and motor level at birth, as opposed to only slight agreement between presurgery anatomical level and motor level at birth. A loss of two or more motor levels between the presurgery and postnatal assessments is associated with a higher presurgery anatomical level and with a larger difference between the presurgery anatomical and motor levels. Consequently, motor level, rather than the anatomical level, should be used for prenatal counseling. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Do FETO CDH survivors need the same follow-up program as non-FETO patients?

Congenital diaphragmatic hernia (CDH) survivors are at risk of developing significant chronic health conditions and disabilities. The main purpose of this study was to compare the outcomes of CDH infants at 2 years of age (2y) according to whether the infants had undergone fetoscopic tracheal occlusion (FETO) during the prenatal period and characterize the relationship between morbidity at 2y and perinatal characteristics. Retrospective cohort single center study. Eleven years of clinical follow-up data (from 2006 to 2017) were collected. Prenatal and neonatal factors as well as growth, respiratory, and neurological evaluations at 2y were analyzed. One hundred and fourteen CDH survivors were evaluated. Failure to thrive (FTT) was present in 24.6% of patients, gastroesophageal reflux disease (GERD) in 22.8%, 28.9% developed respiratory problems, and 22% had neurodevelopment disabilities. Prematurity and birth weight < 2500 g were related to FTT and respiratory morbidity. Time to reach full enteral nutrition and prenatal severity markers seemed to influence all outcomes, but FETO therapy itself only had an effect on respiratory morbidity. Some variables related to postnatal severity (ECMO, patch closure, days on mechanic ventilation, and vasodilator treatment) were associated with almost all outcomes.  Conclusion: CDH patients have specific morbidities at 2y, most of them related to lung hypoplasia severity. Only respiratory problems were related to FETO therapy itself. The implementation of a specific multidisciplinary follow-up program for CDH patients is essential to provide them the best standard of care, but, more severe patients, regardless of whether they received prenatal therapy, need a more intensive follow-up. What is Known: • Antenatal fetoscopic endoluminal tracheal occlusion (FETO) increases survival in more severe congenital diaphragmatic hernia patients. • Congenital diaphragmatic hernia survivors are at risk of developing significant chronic health conditions and disabilities. Very limited data are available about the follow-up in patients with congenital diaphragmatic hernia and FETO therapy. What is New: • CDH patients have specific morbidities at 2 years of age, most of them related to lung hypoplasia severity. • FETO patients present more respiratory problems at 2 years of age but they don't have an increased incidence of other morbidities. More severe patients, regardless of whether they received prenatal therapy, need a more intensive follow-up.

Expectant management for umbilical artery thrombosis in monochorionic diamniotic twin pregnancies: a case report.

BACKGROUND: Thrombosis of one of the umbilical arteries is a rare complication of pregnancy and is associated with adverse pregnancy outcomes, including stillbirth and intrauterine growth restriction. Although extremely rare, umbilical artery thrombosis (UAT) in monochorionic diamniotic twins is difficult to diagnose prenatally and manage. UAT has a poor prognosis and is associated with an increased perinatal mortality rate. In most previous cases, emergency cesarean section was performed or intrauterine fetal death occurred at the time of UAT diagnosis. CASE PRESENTATION: Herein, we report an extremely rare case of sequential UAT in monochorionic diamniotic twins diagnosed via ultrasound at 29+ 5 weeks of gestation in a 34-year-old woman. Following expectant management with intensive monitoring for 16 days, two healthy infants were delivered through an emergency cesarean section. UAT in both fetuses was confirmed by pathological examination. The mother and twins described in this case underwent long-term follow-up and are currently in good health without any complications. CONCLUSIONS: Based on our experience, we suggest that expectant management should be undertaken as long as the mother and infants are stable on ultrasonographic scans and are closely monitored. When UAT is suspected, we believe that the best delivery time should be determined by considering complaints of unusual fetal movements, non-stress test evidence, gestational age, amniotic fluid volume, and blood flow in the umbilical artery, middle cerebral artery, and ductus venosus. Obstetricians should ensure that the patients and their families are clearly informed about all potential risks of expectant management for UAT.

Hemolytic disease of the fetus and newborn: systematic literature review of the antenatal landscape.

BACKGROUND: Prevention of pregnancy-related alloimmunization and the management of hemolytic disease of the fetus and newborn (HDFN) has significantly improved over the past decades. Considering improvements in HDFN care, the objectives of this systematic literature review were to assess the prenatal treatment landscape and outcomes of Rh(D)- and K-mediated HDFN in mothers and fetuses, to identify the burden of disease, to identify evidence gaps in the literature, and to provide recommendations for future research. METHODS: We performed a systematic search on MEDLINE, EMBASE and clinicaltrials.gov. Observational studies, trials, modelling studies, systematic reviews of cohort studies, and case reports and series of women and/or their fetus with HDFN caused by Rhesus (Rh)D or Kell alloimmunization. Extracted data included prevalence; treatment patterns; clinical outcomes; treatment efficacy; and mortality. RESULTS: We identified 2,541 articles. After excluding 2,482 articles and adding 1 article from screening systematic reviews, 60 articles were selected. Most abstracted data were from case reports and case series. Prevalence was 0.047% and 0.006% for Rh(D)- and K-mediated HDFN, respectively. Most commonly reported antenatal treatment was intrauterine transfusion (IUT; median frequency [interquartile range]: 13.0% [7.2-66.0]). Average gestational age at first IUT ranged between 25 and 27 weeks. weeks. This timing is early and carries risks, which were observed in outcomes associated with IUTs. The rate of hydrops fetalis among pregnancies with Rh(D)-mediated HDFN treated with IUT was 14.8% (range, 0-50%) and 39.2% in K-mediated HDFN. Overall mean ± SD fetal mortality rate that was found to be 19.8%±29.4% across 19 studies. Mean gestational age at birth ranged between 34 and 36 weeks. CONCLUSION: These findings corroborate the rareness of HDFN and frequently needed intrauterine transfusion with inherent risks, and most births occur at a late preterm gestational age. We identified several evidence gaps providing opportunities for future studies.

Single fetal demise in monochorionic twins: How to predict cerebral injury in the survivor co-twin?

INTRODUCTION: The aims of the study were to evaluate perinatal outcome in monochorionic (MC) twins complicated with single intrauterine fetal death, spontaneously vs after fetal therapy, and to assess antenatal events that increase the risk of cerebral injury. MATERIAL AND METHODS: Historical cohort study of MC pregnancies with single intrauterine fetal death diagnosed or referred to a tertiary referral hospital (2012-2020). Adverse perinatal outcome included termination of pregnancy, perinatal death, abnormal fetal or neonatal neuroimaging and abnormal neurological development. RESULTS: A total of 68 MC pregnancies with single intrauterine fetal death after 14 weeks of gestation were included. Sixty-five (95.6%) occurred in complicated MC pregnancies (twin to twin transfusion syndrome: 35/68 [51.5%]; discordant malformation: 13/68 [19.1%], selective intrauterine growth restriction: 10/68 [14.7%], twin reversed arterial perfusion sequence: 5/68 [7.3%] and cord entanglement in monoamniotic twins: 2/68 [2.94%]). In 52 cases (76.5%) single intrauterine fetal demise occurred after fetal therapy and in 16 (23.5%) occurred spontaneously. Cerebral damage included 14/68 cases (20.6%): 6/68 cases (8.82%) were prenatal lesions and 8/68 cases (11.8%) were postnatal. Risk of cerebral damage tended to be higher in the spontaneous death group (6/16, 37.5%) compared to the therapy-group (8/52, 15.38%) (p = 0.07). The risk increased with gestational age at intrauterine death (OR 1.21, 95% CI: 1.04-1.41, p = 0.014) and was higher in those surviving co-twins who developed anemia (OR 9.27, 95% CI: 1.50-57.12, p = 0.016). Pregnancies complicated with selective intrauterine growth restriction tended to be at higher risk for neurological damage (OR 2.85, 95% CI: 0.68-11.85, p = 0.15). Preterm birth rate (<37 weeks of pregnancy) was 61.7% (37/60). Seven of eight postnatal cerebral lesions (87.5%) were related to extreme prematurity. Overall perinatal survival rate was 88.3% (57/68) and 7% (4/57) of children had an abnormal neurological outcome. CONCLUSIONS: Risk of cerebral damage in single intrauterine fetal death is especially high when it occurs spontaneously. Gestational age at single intrauterine fetal death, selective intrauterine growth restriction and anemia of the surviving co-twin are the main predictors for prenatal lesions and might be useful in parent counseling. Abnormal postnatal neurological outcome is closely related to extreme prematurity.

Successful prenatal treatment with continuous chronic maternal hyperoxygenation therapy in hypoplastic left heart in two pregnancies: Case report.

Maternal hyperoxygenation (MH) has been studied as a diagnostic tool to evaluate pulmonary vasculature and as a treatment option to improve the growth of fetal left heart in fetuses with left-sided cardiac defects. Chronic maternal hyperoxygenation (CMH) therapy leads to an improvement in fetal pulmonary blood flow resulting in an enhanced venous return to the left heart with increased gestational age. With this manipulation it is anticipated to augment blood flow directed remodeling of the left heart structures and to improve left heart growth spanning from the mitral valve to the aortic isthmus. However, there are concerns about CMH therapy with regard to fetal complications with growth restriction and fetal brain development. Now, with two successful cases we try to discuss this fetal treatment option and related concerns.

Fetal surgery using fetoscopic endoluminal tracheal occlusion for severe congenital diaphragmatic hernia: a single-center experience.

PURPOSE: To provide a comprehensive report of the experience gained in the prenatal treatment of congenital diaphragmatic hernia (CDH) using fetoscopic endoluminal tracheal occlusion (FETO) following its implementation at a newly established specialized fetal medicine center. METHODS: Mothers of fetuses with severe CDH were offered prenatal treatment by FETO. RESULTS: Between 2018 and 2021, 16 cases of severe CDH underwent FETO. The median gestational age (GA) at balloon insertion was 28.4 weeks (IQR 27.8-28.6). The median GA at delivery was 37 weeks (IQR 34.4-37.8). The survival rate was 8/16 cases (50%). None of the survivors required home oxygen therapy at 6 months of age. Comparison between the survivors and deceased showed that survivors had balloon insertion 1 week earlier (27.8 vs. 28.4 weeks, p = 0.007), a higher amniotic fluid level change between pre- to post-FETO (3.4 vs 1.3, p = 0.024), a higher O/E LHR change between pre- to post-FETO (50.8 vs. 37.5, p = 0.047), and a GA at delivery that was 2 weeks later (37.6 vs. 35.4 weeks, p = 0.032). CONCLUSIONS: The survival rate at 6 months of age in cases of severe CDH treated with FETO in our center was 50%. Our new fetal medicine center matches the performance of other leading international centers.