Morphometric Analysis of Spina Bifida after Fetal Repair Shows New Subtypes with Associated Outcomes.

Importance: The binary classification of spina bifida lesions as myelomeningocele (with sac) or myeloschisis (without sac) belies a spectrum of morphologies, which have not been correlated to clinical characteristics and outcomes. Objective: To characterize spina bifida lesion types and correlate them with preoperative presentation and postoperative outcomes. Design: Secondary analysis of images and videos obtained during fetoscopic spina bifida repair surgery from 2020-2023. Setting: Fetal surgery was performed at a quaternary care center. Participants: A prospective cohort of patients referred for fetal spina bifida underwent fetoscopic repair under an FDA-approved protocol. Of 60 lesions repaired, 57 had available images and were included in the analysis. Interventions or Exposures: We evaluated lesion morphology on high-resolution intraoperative images and videos to categorize lesions based on placode exposure and nerve root stretching. Main Outcomes and Measures: The reproducibility of the lesion classification was assessed via Kappa interrater agreement. Preoperative characteristics analyzed include ventricle size, tonsillar herniation level, lower extremities movement, and lesion dimensions. Outcomes included surgical time, need for patch for skin closure, gestational age at delivery, preterm premature rupture of membranes (PPROM), and neonatal cerebrospinal fluid (CSF) diversion. Results: We distinguished five lesion types that differ across a range of sac sizes, nerve root stretching, and placode exposure, with 93% agreement between examiners (p<0.001). Fetal characteristics at preoperative evaluation differed significantly by lesion type, including lesion volume (p<0.001), largest ventricle size (p=0.008), tonsillar herniation (p=0.005), and head circumference (p=0.03). Lesion level, talipes, and lower extremities movement did not differ by type. Surgical and perinatal outcomes differed by lesion type, including need for patch skin closure (p<0.001), gestational age at delivery (p=0.01), and NICU length of stay (p<0.001). PPROM, CSF leakage at birth, and CSF diversion in the NICU did not differ between lesion groups. Linear regression associated severity of ventriculomegaly with lesion type, but not with tonsillar herniation level. Conclusions and Relevance: There is a distinct phenotypic spectrum in open spina bifida with differential baseline presentation and outcomes. Severity of ventriculomegaly is associated with lesion type, rather than tonsillar herniation level. Our findings expand the classification of spina bifida to reveal a spectrum that warrants further study.

Mammalian target of rapamycin inhibitors: A new-possible approach for in-utero medication therapy.

The mammalian/mechanistic target of rapamycin (mTOR) is a protein kinase that plays a crucial role in regulating cellular growth, metabolism, and survival. Although there is no absolute contraindication for the use of mTOR inhibitors during pregnancy, the specific fetal effects remain unknown. Available data from the past 2 decades have examined the use of mTOR inhibitors during pregnancy in patients with solid organ transplantation, showing no clear link to fetal complications or structural abnormalities. Recently, a handful of case reports and series have described transplacental therapy of mTOR inhibitors to control symptomatic and complicated pathologies in the fetus. The effect of these agents includes a significant reduction in lesion size in the fetus and a reduced need for mechanical ventilation in neonates. In this context, we delve into the potential of mTOR inhibitors as in-utero therapy for fetal abnormalities, with a primary focus on lymphatic malformation (LM) and cardiac rhabdomyoma (CR). While preliminary reports underscore the efficacy of mTOR inhibitors for the treatment of fetal CR and fetal brain lesions associated with tuberous sclerosis complex, chylothorax, and LMs, additional investigation and clinical trials are essential to comprehensively assess the safety and efficacy of these medications.

Abnormal Shape and Size of the Cardiac Ventricles Are Associated with a Higher Risk of Neonatal Death in Fetuses with Isolated Left Congenital Diaphragmatic Hernia.

INTRODUCTION: The objective of this study was to evaluate the association between fetal cardiac deformation analysis (CDA) and cardiac function with severe adverse perinatal outcomes in fetuses with isolated left congenital diaphragmatic hernia (CDH). METHODS: CDA in each ventricle (contractility, size, and shape), evaluated by speckle tracking and novel FetalHQ software, and markers of cardiac function (E/A ratios, pulmonary and aortic peak systolic velocities, and sigmoid annular valve diameters), were evaluated in fetuses with isolated left CDH. Two evaluations were performed: at referral (CDA and function) and within 3 weeks of delivery (CDA). Severe adverse neonatal outcomes were considered neonatal death (ND) or survival with CDH-associated pulmonary hypertension (CDH-PH). Differences and associations between CDA, cardiac function, and severe adverse outcomes were estimated. RESULTS: Fifty fetuses were included, and seventeen (34%) had severe adverse neonatal outcomes (11 ND and 6 survivors with CDH-PH). At first evaluation, the prevalence of a small left ventricle was 34% (17/50) with a higher prevalence among neonates presenting severe adverse outcomes (58.8 [10/17] vs. 21.2% [7/33]; p = 0.01; OR, 5.03 [1.4-19.1; p = 0.01]) and among those presenting with neonatal mortality (8/11 [72.7] vs. 9/39 [23.0%]; p = 0.03; OR, 8.9 [1.9-40.7; p = 0.005]). No differences in cardiac function or strain were noted between fetuses with or without severe adverse outcomes. Within 3 weeks of delivery, the prevalence of small left ventricle was higher (19/34; 55.8%) with a more globular shape (reduced transverse/longitudinal ratio). A globular right ventricle was significantly associated with ND or survival with CDH-PH (OR, 14.2 [1.5-138.3]; p = 0.02). CONCLUSION: Fetuses with isolated CDH at risk of perinatal death or survival with CDH-PH had a higher prevalence of a small left ventricle and abnormal shape of the right ventricle.

Fetoscopic laser photocoagulation versus expectant management for stage I twin-to-twin transfusion syndrome: A systematic review and meta-analysis.

To investigate the outcomes of asymptomatic stage I twin-to-twin transfusion syndrome (stage I TTTS) among patients treated with fetoscopic laser photocoagulation (FLP) versus expectant management. Databases such as PubMed, Web of Science and Scopus were systematically searched from inception up to March 1st, 2022. The primary outcome was at least one fetal survival at birth and secondary outcomes included gestational age at delivery, preterm premature rupture of membranes < 32 weeks, preterm birth < 32 weeks, and single and dual fetal survival. Five studies were included in the meta-analysis. There was no significant difference in terms of at least one survival (odds ratio (OR) = 1.40, 95%CI= (0.26, 7.43), P = 0.70), single survival (OR = 0.87, 95%CI= (0.51, 1.48), P = 0.60) and dual survival (OR = 1.63, 95%CI= (0.74, 3.62), P = 0.23) among FLP and expectant groups. Gestational age at delivery (mean difference = 1.19, 95%CI= (-0.25, 2.63), P = 0.10), the risk of PTB<32 weeks (OR = 0.88, 95%CI= (0.50, 1.54), P = 0.65), and pPROM<32 weeks (OR = 1.80, 95% CI= (0.41, 7.98), P = 0.44) were also comparable between the groups. Routine FLP of the placental anastomoses before 26 weeks of gestation is unlikely to be beneficial among asymptomatic stable stage I TTTS patients without cervical shortening as the procedure does not offer a survival advantage compared with expectant management.

Fetal metabolic adaptations to cardiovascular stress in twin-twin transfusion syndrome.

Monochorionic-diamniotic twin pregnancies are susceptible to unique complications arising from a single placenta shared by two fetuses. Twin-twin transfusion syndrome (TTTS) is a constellation of disturbances caused by unequal blood flow within the shared placenta giving rise to a major hemodynamic imbalance between the twins. Here, we applied TTTS as a model to uncover fetal metabolic adaptations to cardiovascular stress. We compared untargeted metabolomic analyses of amniotic fluid samples from severe TTTS cases vs. singleton controls. Amniotic fluid metabolites demonstrated alterations in fatty acid, glucose, and steroid hormone metabolism in TTTS. Among TTTS cases, unsupervised principal component analysis revealed two distinct clusters of disease defined by levels of glucose metabolites, amino acids, urea, and redox status. Our results suggest that the human fetal heart can adapt to hemodynamic stress by modulating its glucose metabolism and identify potential differences in the ability of individual fetuses to respond to cardiovascular stress.

Does Prediction of Neonatal Mortality by the Observed/Expected Lung-To-Head Ratio Change during Pregnancy in Fetuses with Left Congenital Diaphragmatic Hernia?

INTRODUCTION: The aim of this study was to evaluate prediction of neonatal mortality in fetuses with isolated left congenital diaphragmatic hernia (CDH) when the observed/expected lung-to-head ratio (O/E LHR) was estimated at two different gestational time points during pregnancy. METHODS: Forty-four (44) fetuses with isolated left CDH were included. O/E LHR was estimated at the time of referral (first scan) and before delivery (last scan). The main outcome was neonatal death due to respiratory complications. RESULTS: There were 10/44 (22.7%) perinatal deaths. The areas under (AU) the ROC curves were: first scan, 0.76, best O/E LHR cut-off 35.5% with 76% sensitivity and 70% specificity; last scan, AU-ROC 0.79, best O/E LHR cut-off 35.2%, with 79.0% sensitivity and 80% specificity. Considering an O/E LHR cut-off ≤35% to define high-risk fetuses at any examination, prediction for perinatal mortality showed: 80% sensitivity, 73.5% specificity, 47.1% positive and 92.6% negative predictive values, and 3.02 (95% CI 1.59-5.73) positive and 0.27 (95% CI 0.08-0.96) negative likelihood ratios. Prediction was similar in the two evaluations as 16/21 (76.2%) of fetuses considered at risk had an O/E LHR ≤35% in the two examinations; in the remaining 5 cases, two were identified only in the first and three only in the last scan. CONCLUSION: The O/E LHR is a good predictor of perinatal death in fetuses with left isolated CDH. Approximately 80% of fetuses at risk of perinatal death can be identified with an O/E LHR ≤35%, and 90% of them will have similar O/E LHR values at the first and at the last ultrasound examinations prior to delivery. In general, 88.6% of all CDH fetuses have a similar severity classification based on the O/E LHR at the first diagnostic ultrasound or at the ultrasound examination prior to delivery.

Quincke versus Diamond-Tip Needles for Entry in Placental Laser Surgery for Twin-to-Twin Transfusion Syndrome.

INTRODUCTION: Chorioamniotic membrane separation (CAS), preterm prelabor rupture of membranes (PPROM), and preterm delivery (PTD) remain as major complications of fetoscopic laser photocoagulation (FLP) for twin-to-twin transfusion syndrome (TTTS). We sought to examine whether use of Quincke-tip needles for initial entry during FLP reduces the risk of these complications. METHODS: This is a secondary analysis of prospectively collected data from patients that had FLP for TTTS at a single tertiary care center (2011-2021). We excluded patients for whom direct trocar entry was used. Patients for whom a Quincke-tip needle was used were compared to those for whom a diamond-tip needle was used during Seldinger entry. Demographics, ultrasound findings and operative characteristics were compared between groups. Postoperative outcomes and complications (including CAS, PPROM, and PTD) were also compared. Multivariate logistic regression models were fit to assess independent risk factors for complications. RESULTS: 386 patients met inclusion criteria; Quincke-tip needles were used in 81 (21.0%) cases, while diamond-tip needles were used in 305 (79.0%). Rates of CAS (11.1 vs. 9.5%, p = 0.67) and PPROM (44.4 vs. 41.0%, p = 0.57) were similar between groups. Patients in the Quincke-tip group delivered 1.5 weeks earlier than those in the diamond-tip group (30.5 vs. 32.0 weeks, p = 0.01). However, these patients were more likely to be delivered for maternal (35.9 vs. 19.0%) and fetal (23.1 vs. 15.3%) indications (p < 0.01). In multivariate analysis, needle type was not identified as an independent risk factor for PPROM. However, Quincke-tip needle use was associated with PTD less than 32 weeks (aOR 1.74, 95% CI: 1.02-2.97, p = 0.043). CONCLUSION: Membrane complications following FLP were not associated with the needle type used for entry. Earlier delivery in the Quincke-tip group was likely attributable to higher rates of delivery for maternal and fetal indications, and not membrane complications. The needle chosen for entry is likely best determined by operator preference.

The significance of hindbrain herniation reversal following prenatal repair of neural tube defects.

OBJECTIVE: The aim of this study was to determine whether reversal of hindbrain herniation (HBH) on MRI following prenatal repair of neural tube defects (NTDs) is associated with reduced rates of ventriculoperitoneal (VP) shunt placement or endoscopic third ventriculostomy (ETV) within the 1st year of life. METHODS: This is a secondary analysis of prospectively collected data from all patients who had prenatal open repair of a fetal NTD at a single tertiary care center between 2012 and 2020. Patients were offered surgery according to inclusion criteria from the Management of Myelomeningocele Study (MOMS). Patients were excluded if they were lost to follow-up, did not undergo postnatal MRI, or underwent postnatal MRI without a report assessing hindbrain status. Patients with HBH reversal were compared with those without HBH reversal. The primary outcome assessed was surgical CSF diversion (i.e., VP shunt or ETV) within the first 12 months of life. Secondary outcomes included CSF leakage, repair dehiscence, CSF diversion prior to discharge from the neonatal intensive care unit (NICU), and composite neonatal morbidity. Demographic, prenatal sonographic, and operative characteristics as well as outcomes were assessed using standard univariate statistical methods. Multivariate logistic regression models were fit to assess for independent contributions to the primary and secondary outcomes. RESULTS: Following exclusions, 78 patients were available for analysis. Of these patients, 38 (48.7%) had HBH reversal and 40 (51.3%) had persistent HBH on postnatal MRI. Baseline demographic and preoperative ultrasound characteristics were similar between groups. The primary outcome of CSF diversion within the 1st year of life was similar between the two groups (42.1% vs 57.5%, p = 0.17). All secondary outcomes were also similar between groups. Patients who had occurrence of the primary outcome had greater presurgical lateral ventricle width than those who did not (16.1 vs 12.1 mm, p = 0.02) when HBH was reversed, but not when HBH was persistent (12.5 vs 10.7 mm, p = 0.49). In multivariate analysis, presurgical lateral ventricle width was associated with increased rates of CSF diversion before 12 months of life (adjusted OR 1.18, 95% CI 1.03-1.35) and CSF diversion prior to NICU discharge (adjusted OR 1.18, 95% CI 1.02-1.37). CONCLUSIONS: HBH reversal was not associated with decreased rates of CSF diversion in this cohort. Predictive accuracy of the anticipated benefits of prenatal NTD repair may not be augmented by the observation of HBH reversal on MRI.

Cryopreserved human umbilical cord as a meningeal patch during in utero spina bifida repair in a modified ovine model.

OBJECTIVE: Despite in utero spina bifida (SB) repair, more than two-thirds of patients with SB are unable to ambulate independently, and 1 in 4 children need surgery for tethered cord by school age. The objective of this study was to test the cryopreserved human umbilical cord (HUC) as an antiscarring material to reduce tethering and improve function in a modified in utero SB repair model. METHODS: An SB defect (L2-6 levels) without myelotomy was created in fetuses of timed-pregnant ewes at gestational day (GD) 75. On GD 96, the fetal defect was exposed, and the arachnoid layer was removed to disrupt the barrier and expose the spinal cord to simulate human in utero SB repair. The fetuses were randomly assigned to two groups according to the method used to cover the spinal cord: the conventional repair (CR) group, for which myofascial closure was used (n = 7), and the HUC meningeal patch group, for which HUC was used as a meningeal patch (n = 6), followed by primary skin closure. The lambs were delivered at GD 140. Blinded clinical assessment of spinal cord function was performed using the Texas Spinal Cord Injury Scale (TSCIS). Histology of the spine was performed for quantitative assessment of spinal cord tethering, inflammatory markers, and arachnoid layer regeneration. RESULTS: The TSCIS scores were significantly lower in the CR than the HUC meningeal patch group (p = 0.0015) and the controls (p = 0.0018). The loss of spinal cord function in the CR group was mainly due to ataxia and loss of proprioception (p = 0.01 and 0.005 vs control and HUC, respectively). The histology at the repair site showed higher rates of spinal cord tethering in the CR lambs than the HUC lambs at all levels of the repair site (p = 0.01 and 0.02 vs control and HUC, respectively). In the CR with tethering compared with the HUC repair, there was a lower arachnoid layer covering at the repair site (p = 0.001). There was greater astrocyte activation in the posterior column in the CR than in the HUC repair group (p = 0.01). CONCLUSIONS: In a modified ovine SB model, the HUC as a meningeal patch allows regeneration of the arachnoid layer, prevents spinal cord tethering, and improves spinal cord function after in utero SB repair.

Fetal Repair of Neural Tube Defects.

Myelomeningocele is the most common congenital neurologic defect, and the only nonlethal disease addressed by fetal surgery. A randomized control trial has established amelioration of the Arnold-Chiari II malformation, reduced ventriculoperitoneal shunt rate, and improvement in distal neurologic function in patients that receive in utero repair. Long-term follow-up of these school-age children demonstrates the persistence of these effects. The use of stem cells in fetal repair is being investigated to further improve distal motor function.

Current Status of the Workforce and Training at Fetal Therapy Centers in North America.

INTRODUCTION: We sought to characterize the current workforce and training for fetal intervention procedures at fetal centers in North America. METHODS: An anonymous electronic survey was developed to query the 34 centers in the North American Fetal Treatment Network regarding the demographics and training of their faculty. Telephone surveys were conducted with directors of known fetal intervention fellowships. RESULTS: More than 50% of maternal-fetal medicine (MFM) faculty at fetal centers were female; more than two-thirds of pediatric surgical faculty were male. Most of the training of faculty was undertaken by visiting more experienced centers or having new faculty work with more experienced ones at the same center. Current fetal intervention fellowships appear to achieve levels of competency for intrauterine transfusions and laser therapy for twin-twin transfusion syndrome. Two-thirds of centers stated that they would be able to offer a position to an MFM who completed a formal fellowship in fetal intervention. CONCLUSION: A collaborative effort should be undertaken to establish formal fellowships in fetal medicine and intervention.

Leaving the Placenta In Situ in Placenta Accreta Spectrum Disorders: A Single-Center Case Series.

OBJECTIVE: The most common treatment for placenta accreta spectrum (PAS) disorders is planned primary cesarean hysterectomy. However, other management strategies may improve outcomes and/or allow fertility preservation. The objective of this study was to describe the course and outcomes of patients with PAS managed by leaving the placenta in situ. STUDY DESIGN: This is a series of 11 patients with PAS managed by leaving the placenta in situ at a single academic center in the United States from 2015 to 2022. The approach described involves delivery of the fetus via cesarean, no attempt at placental removal, closure of the hysterotomy, prophylactic intravenous antibiotics for up to 1 week, and close outpatient follow-up until the uterus is empty. RESULTS: The uterus was successfully preserved in six (55%), minimally invasive hysterectomy was performed in four (36%), and abdominal hysterectomy was performed in 1 (9%). During cesarean delivery, the median estimated blood loss was 650mL (range: 200-1,000mL). The majority of patients had no vaginal discharge for several weeks after delivery, followed by brown or bloody discharge, and intermittent mild-to-moderate cramping. The median time to resolution of PAS was 18 weeks in patients with successful uterine preservation (range: 5-25 weeks). Indications for hysterectomy included hemorrhage (n=1), coagulopathy (n=1), endomyometritis (n=2), and pain (n=1), and these occurred at a median of 5 weeks postpartum (range: 1-25 weeks). Four patients had subsequent pregnancies of whom three were live births at or near term and one was a spontaneous abortion at 19 weeks. CONCLUSION: Leaving the placenta in situ may be an appropriate management strategy for some carefully selected and counseled patients with PAS. KEY POINTS: · Overall, 55% had uterine preservation (6/11).. · Minimally invasive approach in 80% of hysterectomies (4/5).. · Of patients, 67% with uterine preservation had subsequent pregnancies (4/6)..

Human M1 macrophages express unique innate immune response genes after mycobacterial infection to defend against tuberculosis.

Mycobacterium tuberculosis (Mtb) is responsible for approximately 1.5 million deaths each year. Though 10% of patients develop tuberculosis (TB) after infection, 90% of these infections are latent. Further, mice are nearly uniformly susceptible to Mtb but their M1-polarized macrophages (M1-MΦs) can inhibit Mtb in vitro, suggesting that M1-MΦs may be able to regulate anti-TB immunity. We sought to determine whether human MΦ heterogeneity contributes to TB immunity. Here we show that IFN-γ-programmed M1-MΦs degrade Mtb through increased expression of innate immunity regulatory genes (Inregs). In contrast, IL-4-programmed M2-polarized MΦs (M2-MΦs) are permissive for Mtb proliferation and exhibit reduced Inregs expression. M1-MΦs and M2-MΦs express pro- and anti-inflammatory cytokine-chemokines, respectively, and M1-MΦs show nitric oxide and autophagy-dependent degradation of Mtb, leading to increased antigen presentation to T cells through an ATG-RAB7-cathepsin pathway. Despite Mtb infection, M1-MΦs show increased histone acetylation at the ATG5 promoter and pro-autophagy phenotypes, while increased histone deacetylases lead to decreased autophagy in M2-MΦs. Finally, Mtb-infected neonatal macaques express human Inregs in their lymph nodes and macrophages, suggesting that M1 and M2 phenotypes can mediate immunity to TB in both humans and macaques. We conclude that human MФ subsets show unique patterns of gene expression that enable differential control of TB after infection. These genes could serve as targets for diagnosis and immunotherapy of TB.

The Delphi definition for selective fetal growth restriction may not improve detection of pathologic growth discordance in monochorionic twins.

BACKGROUND: A consensus definition of selective fetal growth restriction in monochorionic diamniotic twins was recently proposed following a Delphi procedure involving an international panel of experts. The new definition augments the traditional definition with additional sonographic criteria. OBJECTIVE: We sought to determine whether the augmentations of the "Delphi definition" identified additional morbidity and mortality compared with a traditional definition. Furthermore, we sought to determine the benefit of each definition in identifying pathologic growth restriction relative to uncomplicated monochorionic diamniotic twins. STUDY DESIGN: This was a retrospective analysis of unselected monochorionic diamniotic twins that underwent fortnightly ultrasound surveillance at a single center between 2011 and 2020. Patients with concomitant twin-to-twin transfusion syndrome, twin anemia polycythemia sequence, or twin reversed arterial perfusion sequence at the time of diagnosis of selective fetal growth restriction were excluded. The diagnosis of selective fetal growth restriction using the Delphi definition required either an estimated fetal weight of <3rd percentile or presence of 2 of 4 observations in the smaller twin: (1) estimated fetal weight of <10th percentile, (2) estimated fetal weight discordance of >25% compared with the larger twin, (3) abdominal circumference of <10th percentile, (4) umbilical artery pulsatility index of >95th percentile. Diagnosis using the traditional definition required an estimated fetal weight of <10th percentile and an estimated fetal weight discordance of >25%. To determine the efficacy of the augmentations in the Delphi definition, 3 groups were compared: group I, uncomplicated monochorionic diamniotic twins; group II, twins with selective fetal growth restriction using the traditional definition (and therefore the Delphi definition); and group III, twins with selective fetal growth restriction solely using the Delphi definition. Demographic characteristics, subsequent development of twin-to-twin transfusion syndrome or twin anemia polycythemia sequence, pregnancy outcomes, and neonatal outcomes were compared. RESULTS: There were 325 patients with monochorionic diamniotic twins that met inclusion criteria. Of these, 213 (66%; group I) were uncomplicated, 37 (11%; group II) met the traditional definition for selective fetal growth restriction, and 112 (35%) met the Delphi definition for selective fetal growth restriction with 75 (67%) meeting solely the Delphi definition (group III). Demographic characteristics were similar between groups. Patients in group II delivered earlier than uncomplicated twins (32.1 vs 35.7 weeks of gestation; P<.01) and patients in group III (32.1 vs 35.6 weeks of gestation; P<.01). Furthermore, they were more likely to have critical umbilical artery Doppler abnormalities (38% vs 4%; P<.01) and be delivered for deteriorating fetal status (30% vs 5%; P<.01) than those in group III. Overall, survival was lower in group II than groups I and III (89% vs 96% and 100%, respectively; P=.04). Moreover, composite neonatal morbidity and mortality were greater in group II (30%) than either group I (6%; P<.01) or group III (9%; P<.01). The rates of composite neonatal morbidity and mortality were similar between groups I and III (P=.28). CONCLUSION: The addition of abdominal circumference and umbilical artery pulsatility index thresholds and isolated estimated fetal weight of <3%, as proposed by the Delphi definition, increased the diagnosis of selective fetal growth restriction; however, there was no added benefit in the identification of growth discordant pregnancies at risk of adverse outcomes. Prospective analysis of monochorionic diamniotic twins is required to contextualize these findings.

Planned versus Unplanned Delivery for Placenta Accreta Spectrum.

OBJECTIVE: Women with placenta accreta spectrum (PAS) having an unplanned delivery may have worse outcome compared with women with a planned delivery. The primary objective of this study was to compare severe maternal morbidity among women with PAS who had a planned scheduled delivery versus an unplanned delivery. Secondary objective was to compare neonatal outcomes. STUDY DESIGN: Retrospective cohort study at two tertiary centers (January 2009 to June 2019) of all women who underwent a hysterectomy with a histologic proven PAS. Primary outcome was severe maternal morbidity which defined as any of the following: transfusion of ≥4 RBC units or ureter/bowel injury. Neonatal outcome was a composite neonatal morbidity defined as any of the following: Apgar score's < 5 at 5 minutes, mechanical ventilation, or respiratory distress syndrome. Maternal demographic, clinical, and sonographic characteristics were compared between the two groups (planned vs. unplanned). Descriptive statistics were used as appropriate, and a statistical significance was established if p-value was < 0.05. RESULTS: Of 109 women who underwent cesarean hysterectomy for PAS, 41 (37.6%) had an unplanned delivery. There was no significant difference in the number of previous cesarean deliveries or ultrasound findings between the two groups. Women with an unplanned delivery were more likely to bleed during pregnancy than those that had a planned delivery (p = 0.04). Women with unplanned delivery had lower gestational age at delivery (30.3 vs. 33.8 weeks, p = 0.001) had a 75% higher rate of the primary outcome (63 vs. 36%, p = 0.007) and had a higher rate of intensive care unit admissions (39 vs. 17.7%, p = 0.01) compared with women with a planned delivery. The neonatal morbidity did not differ between the two groups. CONCLUSION: Since unplanned cesarean hysterectomy among women with PAS occurs in 40% and is associated with significantly higher morbidity, interventions are needed to mitigate the rate of adverse outcomes. KEY POINTS: · Only 60% of women with PAS reached planned delivery at 34 weeks.. · PAS unplanned delivery is associated with high morbidity.. · Some women with PAS may need a scheduled earlier delivery..

Allografts for Skin Closure during In Utero Spina Bifida Repair in a Sheep Model.

OBJECTIVES: Use of off-label tissue graft materials, such as acellular dermal matrix (ADM), for in utero repair of severe spina bifida (SB), where primary skin layer closure is not possible, is associated with poor neurological outcomes. The cryopreserved human umbilical cord (HUC) patch has regenerative, anti-inflammatory, and anti-scarring properties, and provides watertight SB repair. We tested the hypothesis that the HUC is a superior skin patch to ADM for reducing inflammation at the repair site and preserving spinal cord function. METHODS: In timed-pregnant ewes with twins, on gestational day (GD) 75, spina bifida was created without a myelotomy (functional model). On GD 95, repair was performed using HUC vs. ADM patches (randomly assigned) by suturing them to the skin edges. Additionally, full thickness skin closure as a primary skin closure (PSC) served as a positive control. Delivery was performed on GD 140, followed by blinded to treatment neurological assessments of the lambs using the Texas Spinal Cord Injury Scale (TSCIS) for gait, proprioception, and nociception. Lambs without spina bifida were used as controls (CTL). Ex vivo magnetic resonance imaging of spines at the repair site were performed, followed by quantitative pathological assessments. Histological assessments (blinded) included Masson's trichrome, and immunofluorescence for myeloperoxidase (MPO; neutrophils) and for reactive astrocytes (inflammation) by co-staining vimentin and GFAP. RESULTS: The combined hind limbs' TSCIS was significantly higher in the HUC group than in ADM and PSC groups, p = 0.007. Both ADM and PSC groups exhibited loss of proprioception and mild to moderate ataxia compared to controls. MRI showed increased pathological findings in the PSC group when compared to the HUC group, p = 0.045. Histologically, the meningeal layer was thickened (inflammation) by 2-3 fold in ADM and PSC groups when compared to HUC and CTL groups, p = 0.01. There was lower MPO positive cells in the HUC group than in the ADM group, p = 0.018. Posterior column astrocyte activation was increased in ADM and PSC lambs compared to HUC lambs, p = 0.03. CONCLUSION: The HUC as a skin patch for in utero spina bifida repair preserves spinal cord function by reducing underlying inflammation when compared to ADM.

Risk Factors and Outcomes Following Septostomy during Fetoscopic Surgery for Twin-to-Twin Transfusion Syndrome.

Fetoscopic laser photocoagulation (FLP) of placental anastomoses is the preferred treatment for twin-to-twin transfusion syndrome (TTTS). Iatrogenic septostomy (IOS) during FLP is associated with increased risk of neonatal morbidity and mortality. We sought to identify risk factors for IOS and quantify the resultant outcomes. This is a secondary analysis of prospectively collected cases of TTTS in monochorionic diamniotic twins following FLP at a single center. Pre-operative ultrasound characteristics and operative technique (i.e., cannula size, total energy used) were compared between cases with vs. without IOS. Pregnancy and neonatal outcomes were also compared. Of 475 patients that had FLP, 33 (7%) were complicated by IOS. There was no association between operative technique and IOS. IOS was more common with later diagnosis, but less likely when selective fetal growth restriction (sFGR) was present. Survival was similar between groups (76% vs. 76% dual survivors, p = 0.95); however, IOS was associated with earlier delivery (29.7 vs. 32.0 wks, p < 0.01) and greater composite neonatal morbidity (25% vs. 8% in both twins, p = 0.02). Risks of IOS at greater gestational ages without sFGR may be related to a larger collapsed intervening membrane area and the resulting increased risk of puncture on entry.

Predicting fetal and neonatal demise after fetoscopy for twin-twin transfusion syndrome using recursive partitioning.

OBJECTIVE: Donor demise after laser surgery for twin-twin transfusion syndrome (TTTS) is well-characterized, but recipient demise is not, nor is neonatal death. This study aims to characterize factors associated with recipient death, donor death, and dual twin death after laser, both before and after birth. METHODS: This is a prospective cohort study of monochorionic twin pairs who underwent laser ablation for TTTS. Risk factors for fetal and neonatal death of both twins were identified using univariable analysis and recursive partitioning, a novel statistical method to quantify contributions of each factor to outcomes. RESULTS: In 413 twin pairs, death of both twins occurred in 9.2% (38/413), donor death in 12.1% (50/413), and recipient death in 2.4% (10/413). Recursive partitioning showed that gestational age at delivery predicts dual twin death (below 23.7 weeks, likely [p < 0.001], above 28.3 weeks, unlikely [p = 0.004]). Abnormal umbilical artery Doppler and weight discordance predict donor demise (p < 0.001 and p = 0.033, respectively). Cervical length under 16 mm predicts neonatal death of both twins (p < 0.001). CONCLUSIONS: Parents can gain individualized information about the survival of each fetus based on variables available from preoperative and delivery variables. Short cervix and premature delivery cause significant mortality in TTTS.

Low Transverse versus Midline Abdominal Skin Incisions for in utero Spina Bifida Repair.

OBJECTIVE: The 2 types of maternal skin incisions for in utero spina bifida repair are low transverse (LT) incision perceived to be cosmetic benefit and midline longitudinal (ML) incision, typically associated with a reduction in surgical time and lower blood loss. Our objective was to compare short- and long-term outcomes associated with these 2 types of skin incisions following in utero spina bifida repair. METHODS: Prospective observational cohort of 72 patients undergoing fetal spina bifida repair at a single institution between September 2011 and August 2018. The decision for the type of incision was at the discretion of the surgeons. The primary outcome was total operative time. Secondary outcomes included an analog scale of wound pain score on postoperative day 3, duration of postoperative stay, and postoperative wound complications within the first 4 weeks. The Patient Scar Assessment Questionnaire, a validated questionnaire, was obtained for all patients (≥6 months from delivery) using 4 categories (appearance, consciousness, satisfaction with appearance and with symptoms), with higher scores reflecting a poorer perception of the scar. RESULTS: There were 43 women (59.7%) in the LT group and 29 (40.3%) in the ML group. In all patients, the same incision was used during cesarean delivery. The total operative time was higher in the LT group by 33 min (p < 0.001), primarily due to abdominal wall incision time (open and closure). No significant differences were found between the groups in pain score, length of postoperative stay, or the rate of wound complications. Fifty-three patients (73.6%) responded to the questionnaire, 36/43 from the LT group and 17/29 from the ML group. There was no difference in the scores of appearance, consciousness, and satisfaction with appearance and symptoms between the groups. CONCLUSION: ML incisions shorten operative times without altering long-term incision-related satisfaction when compared to LT incisions.

Spontaneous twin anemia polycythemia sequence: diagnosis, management, and outcome in an international cohort of 249 cases.

BACKGROUND: Twin anemia polycythemia sequence is a chronic form of unbalanced fetofetal transfusion through minuscule placental anastomoses in monochorionic twins, leading to anemia in the donor and polycythemia in the recipient. Owing to the low incidence of twin anemia polycythemia sequence, data on diagnosis, management, and outcome are limited. OBJECTIVE: This study aimed to investigate the diagnosis, management, and outcome in a large international cohort of spontaneous twin anemia polycythemia sequence. STUDY DESIGN: Data from the international twin anemia polycythemia sequence registry, retrospectively collected between 2014 and 2019, were used for this study. A total of 17 fetal therapy centers contributed to the data collection. The primary outcomes were perinatal mortality and severe neonatal morbidity. Secondary outcomes included a risk factor analysis for perinatal mortality and severe neonatal morbidity. RESULTS: A total of 249 cases of spontaneous twin anemia polycythemia sequence were included in this study, 219 (88%) of which were diagnosed antenatally and 30 (12%) postnatally. Twin anemia polycythemia sequence was diagnosed antenatally at a median gestational age of 23.7 weeks (interquartile range, 9.7-28.8; range, 15.1-35.3). Antenatal management included laser surgery in 39% (86 of 219), expectant management in 23% (51 of 219), delivery in 16% (34 of 219), intrauterine transfusion (with partial exchange transfusion) in 12% (26 of 219), selective feticide in 8% (18 of 219), and termination of pregnancy in 1% (3 of 219) of cases. Perinatal mortality rate was 15% (72 of 493) for the total group, 22% (54 of 243) for donors, and 7% (18 of 242) for recipients (P<.001). Severe neonatal morbidity occurred in 33% (141 of 432) of twins with twin anemia polycythemia sequence and was similar for donors (32%; 63 of 196) and recipients (33%; 75 of 228) (P=.628). Independent risk factors for spontaneous perinatal mortality were donor status (odds ratio, 3.8; 95% confidence interval, 1.9-7.5; P<.001), antenatal twin anemia polycythemia sequence stage (odds ratio, 6.3; 95% confidence interval, 1.4-27.8; P=.016 [stage 2]; odds ratio, 9.6; 95% confidence interval, 2.1-45.5; P=.005 [stage 3]; odds ratio, 20.9; 95% confidence interval, 3.0-146.4; P=.002 [stage 4]), and gestational age at birth (odds ratio, 0.8; 95% confidence interval, 0.7-0.9; P=.001). Independent risk factors for severe neonatal morbidity were antenatal twin anemia polycythemia sequence stage 4 (odds ratio, 7.9; 95% confidence interval, 1.4-43.3; P=.018) and gestational age at birth (odds ratio, 1.7; 95% confidence interval, 1.5-2.1, P<.001). CONCLUSION: Spontaneous twin anemia polycythemia sequence can develop at any time in pregnancy from the beginning of the second trimester to the end of the third trimester. Management for twin anemia polycythemia sequence varies considerably, with laser surgery being the most frequent intervention. Perinatal mortality and severe neonatal morbidity were high, the former especially so in the donor twins.