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.

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.

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)..

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..

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.

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.

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.

Pregnancy outcomes associated with chorioamnion membrane separation severity following fetoscopic laser surgery for twin-twin transfusion syndrome.

OBJECTIVE: We tested the hypothesis that increasing severity of chorioamnion membrane separation (CAS) after fetoscopic laser surgery (FLS) for twin-twin transfusion syndrome (TTTS) is associated with worse pregnancy outcomes. METHODS: Prospective cohort of patients undergoing FLS for TTTS between 2011 and 2018. CAS was defined as separation of fetal membranes from the uterine wall on post-operative ultrasound. Patient groups were defined: Group 1: No CAS; Group 2: CAS lower than 50th centile; Group 3: CAS upper than 50th centile or complete CAS. Comparative analysis was performed. RESULTS: Of 387 patients meeting inclusion criteria, 29 (7.5%) had CAS (median 9.8 mm [4.9-30.8 mm]). Group 1 patients were more likely to undergo FLS at later gestational age, had increased recipient maximum vertical pocket, and higher amnioreduction volume than Group 3. Group 3 had higher rates of preterm premature rupture of membrane, delivered earlier and were more likely to terminate than Group 1. Group 2 had fewer neonatal survivors than Group 1. Survival analysis for gestational age at delivery and Cox proportional hazards model indicated increased risk for early delivery in Groups 2 and 3 compared with Group 1. CONCLUSIONS: Patients with CAS ≥9.8 mm or complete CAS after FLS for TTTS had worse obstetric and neonatal outcomes.

Prenatal and Postnatal Imaging Findings After Fetal Repair of Spinal Dysraphisms Using Cryopreserved Human Umbilical Cord Patch: A Case Series of 4 Patients.

We describe a case series of imaging findings of 4 patients who underwent spinal dysraphisms repair in utero with novel patch material, cryopreserved human umbilical cord, in our institution. In our study, the prenatal and postnatal magnetic resonance imaging and ultrasound are reviewed and showed cord tethering and syrinx progression in all cases. Our report is the first description of magnetic resonance imaging and ultrasound findings in the context of using this novel patch in severe cases of spinal dysraphisms.

Fortnightly surveillance of monochorionic diamniotic twins for twin to twin transfusion syndrome: Compliance and effectiveness.

OBJECTIVES: To determine the compliance and effectiveness of fortnightly ultrasound surveillance for detection of twin-twin transfusion syndrome (TTTS) in monochorionic diamniotic (MCDA) twin gestations. METHODS: This is a retrospective study of ultrasound surveillance of MCDA twins for TTTS. Our surveillance protocol requires fortnightly ultrasounds starting at 16 weeks of gestational age (GA) continuing until delivery. Compliance was assessed by determining the GA of surveillance initiation and time between ultrasounds. GA and Quintero Stage at diagnosis were evaluated to determine whether TTTS was detected prior to advanced disease (Quintero Stage III +) or fetal demise. RESULTS: Of 442 women, 264 (59.7%) initiated surveillance after 16 weeks; follow-up ultrasounds were late in 17.4% of cases. TTTS was diagnosed in 43 (9.7%) women at a median GA of 19.7 [17.4, 23.9] weeks. Of 25/43 (58.1%) cases diagnosed during protocol compliance, 12 had advanced disease and two had fetal demise. A similar proportion of diagnoses (n = 18), made while non-compliant, exhibited advanced disease (11/18, 61.1%, P = .40). Thirteen diagnoses occurred during periods of increased ultrasound frequency due to abnormalities (ie, fluid/estimated fetal weight discrepancies or Doppler abnormalities). CONCLUSIONS: In this population, fortnightly ultrasound compliance was suboptimal. Advanced disease and fetal demise occurred during protocol compliance.

Steroid Hormone Levels in Recipient Amniotic Fluid in Twin-Twin Transfusion Syndrome and Their Association with Preterm Delivery.

OBJECTIVE: Preterm delivery following fetoscopic laser surgery (FLS) of twin-twin transfusion syndrome (TTTS) is associated with severe perinatal morbidity and mortality. The role of steroid hormones in amniotic fluid (AF) after FLS remains unknown. STUDY DESIGN: A prospective cohort study of consecutive case series of FLS for TTTS was performed from April 2012 to February 2017. Cases were divided into early (≤27 weeks) spontaneous preterm delivery (ED) and late delivery (LD; ≥34 weeks) following FLS and compared. AF supernatants were assessed for protein, estradiol, progesterone and cortisol levels (using the ELISA kit), and normalized to total protein levels to adjust for dilution. RESULTS: A total of 294 consecutive cases of FLS for TTTS in monochorionic-diamniotic twins were performed during the study period. AF was available in 44 ED patients and 50 LD patients. On logistic regression, ED was associated with higher normalized progesterone levels (odds ratio [OR]: 1.25; 95% confidence interval [CI]: 1.12-1.41), lower normalized cortisol (OR: 0.78; 95% CI: 0.64-0.96), and higher estradiol levels (OR: 1.3; 95% CI: 1.03-1.63). CONCLUSION: Elevated AF normalized progesterone and estradiol, and lower normalized cortisol levels were associated with ED. This novel finding requires further exploration to establish the molecular mechanism operational in pregnancies complicated by TTTS to potentially prevent early preterm birth after fetal surgery.

Fractional Limb Volume in Spina Bifida Fetuses as an Assessment Tool for Postnatal Ambulation.

BACKGROUND: Prenatal fractional limb volume (FLV) can be used to assess muscle atrophy in fetuses with myelomeningocele. OBJECTIVE: We hypothesize that FLV in fetal myelomeningocele (fMMC) repair is different from postnatal repair (PNR). Assessing intrauterine muscle development can predict ambulation. METHODS: A prospective observational study was performed from July 2012 to April 2016. Demographics, clinical outcomes, and FLV of the fetal thigh were assessed by ultrasound. Ambulation videos were collected from patients over 30 months of age. FLV was compared between the fMMC and PNR groups and between ambulators and non-ambulators. Two-sample t test, ANOVA, Spearman's rho correlation, and Bland-Altman plots were used for analysis. A p value <0.05 was used for statistical significance. RESULTS: Fifty-nine patients were included, 24 had fMMC and 35 had PNR. Videos were obtained in 47 cases (73%). There was no difference in baseline demographics between the groups. There was no significant change in the fMMC group between the FLV at initial presentation and the repeat at 34 weeks gestation (54.5 ± 28.2 and 62.2% ± 16.4; p = 0.6). In contrast, the FLV in the PNR decreased between the initial evaluation and the repeat at 34 weeks (54.1 ± 27.7 to 35.8 ± 34.1%; p = 0.04). FLV at 34 weeks gestation was higher in the fMMC group as compared to the PNR group (62.2 ± 16.4 vs. 35.8 ± 34.1%; p = 0.02). There was no difference in FLV between ambulators and non-ambulators either at initial evaluation (p = 0.8) or at 34 weeks gestation (p = 0.6). CONCLUSION: Lower FLV in the PNR group compared to fMMC may suggest in utero muscle atrophy. No correlation was seen between FLV and subsequent ambulation; however, future larger studies may be needed.

Distance Traveled to a Fetal Center and Pregnancy Outcomes in Twin-Twin Transfusion Syndrome.

BACKGROUND: Fetoscopic laser photocoagulation (FLP) is the definitive treatment for twin-twin transfusion syndrome (TTTS). Due to variability in geographic proximity to high-volume fetal centers, many patients travel great distances to receive experienced care. We sought to determine whether distance traveled (DT) is associated with gestational age (GA) at delivery and neonatal survival. METHODS: A prospective cohort study of patients within the continental United States referred to our center between September 23, 2011 and July 25, 2018 undergoing planned FLP for TTTS (n = 393; GA 20.6 ± 2.5 weeks; stage I: n = 50; stage II: n = 118; stage III: n = 208; stage IV: n = 17) was performed. The great-circle distance to our center was calculated using patients' home zip codes. DT was stratified into groups containing equal patient numbers and pregnancy outcomes assessed. RESULTS: A total of 393 patients met the inclusion criteria. The threshold distance from our center was <250 miles (n = 181), 250-499 miles (n= 119), and ≥500 miles (n = 93). There was no significant difference between any of the preoperative variables among the three groups, with the exception of race and rural status. Furthermore, there was no significant association between DT and GA at delivery (p = 0.34), time interval from procedure to delivery (p = 0.37), and the number of neonatal survivors (p= 0.21). Preterm premature rupture of membranes (PPROM) at <34 weeks was highest (47.9%, p = 0.04) in the group traveling 250-499 miles. CONCLUSION: To our knowledge, this is the largest study to show that in TTTS, DT is not associated with GA at delivery, time interval from procedure to delivery, or neonatal survival. Although PPROM at <34 weeks was higher in the group traveling 250-499 miles, there was no significant difference in GA at delivery. While patients with advanced disease may choose to seek treatment based on proximity, traveling long distances does not adversely affect pregnancy outcomes.

Neonatal Outcomes and Maternal Characteristics in Monochorionic Diamniotic Twin Pregnancies: Uncomplicated versus Twin-to-Twin Transfusion Syndrome Survivors after Fetoscopic Laser Surgery.

Preterm birth remains a major complication of fetal laser surgery (FLS) due to twin-to-twin transfusion syndrome (TTTS). OBJECTIVES: We tested the hypothesis that neonatal outcomes in fetuses born at >24 weeks are worse in TTTS survivors compared to uncomplicated monochorionic diamniotic (MCDA) twins. METHODS: 196 patients with TTTS treated with laser therapy and 91 uncomplicated MCDA gestations were compared. Neonatal outcomes included respiratory distress syndrome (RDS), transient tachypnea of the newborn (TTN), bronchopulmonary dysplasia, intraventricular hemorrhage, necrotizing enterocolitis, and neonatal death. Risk factors assessed were TTTS, maternal age, maternal body mass index, race, premature prolonged rupture of membranes, stage of TTTS, parity, and gestational age (GA) at delivery. RESULTS: GA at delivery was lower in the TTTS group (31.0 ± 4.6 vs. 33.5 ± 2.4 weeks, p < 0.001). RDS and TTN occurred at higher rates in the TTTS than in the uncomplicated MCDA group. After multivariate logistic regression, the only factor significantly associated with the composite adverse outcome was GA at delivery (OR 0.61; 95% CI: 0.58-0.7). CONCLUSION: TTTS twins treated with FLS are deliver 2.5 weeks earlier than uncomplicated MCDA twins. Respiratory complications were significantly higher in TTTS twins and were mainly the consequence of the early GA at delivery.

The utilization of prenatal microarray: A survey of current genetic counseling practices and barriers.

OBJECTIVE: We evaluated what prenatal genetic counselor's (GCs) practices, attitudes, and barriers are in regards to prenatal microarray since the publication of the American College of Obstetricians and Gynecologists (ACOG) and the Society for Maternal-Fetal Medicine (SMFM) guidelines for microarray use. METHODS: This was a survey-based cross-sectional study of English-speaking, board certified or eligible GCs who currently practice prenatal genetic counseling. RESULTS: Of 192 respondents, 183 (95%) have incorporated chromosome microarray (CMA) into clinical practice, with 64% believing that the benefits of CMA outweigh the harms and 52% agreeing that CMA should be offered to all women regardless of indication. Those who reported being experts/comfortable in their knowledge of CMA (85%) and familiar with current clinical guidelines (86%) were significantly more likely to offer CMA to patients undergoing invasive testing and patients with fetal anomalies. Patient-specific concerns were the largest reported barrier (51%) when GCs do not offer CMA to patients. CONCLUSION: Our study demonstrates GCs follow guidelines for CMA use when specific indications are involved, but further guidelines are needed regarding CMA use for other routine indications where utility of CMA is not clearly understood. On this basis, ACOG and SMFM should continue revising their guidelines as more information comes to light regarding utility of prenatal CMA for all indications, and organizations like the National Society of Genetic Counselors (NSGC) should consider publishing guidelines on prenatal CMA that are specialized to the GCs sphere of practice.

Early Administration of Magnesium Sulfate during Open Fetal Myelomeningocele Repair Reduces the Dose of Inhalational Anesthesia.

INTRODUCTION: Optimal uterine relaxation is achieved through higher minimum alveolar concentration (MAC) of inhalational anesthetics, increasing risks to mother and fetus. Our objective was to determine if earlier administration of magnesium sulfate would reduce the requirement of inhalational anesthetics in fetal myelomeningocele repair. MATERIALS AND METHODS: Prospective observational study of fetal myelomeningocele repair was performed from September 2011 to August 2017. Groups compared were: (1) magnesium sulfate at uterine closure; (2) magnesium sulfate at maternal skin incision. Maternal demographics, anesthetic agents, intraoperative complications, and pregnancy outcomes were reviewed. A Student t test was used for analysis. RESULTS: There were 30 cases in group 1 and 21 cases in group 2. There was no difference in gestational age at intervention (24.92 ± 0.62 vs. 25.22 ± 0.47 weeks, p = 0.07) or at delivery (34.83 ± 2.77 vs. 33.98 ± 3.83 weeks, p = 0.38) between groups 1 and 2, respectively. The maximum MAC of sevoflurane was significantly lower in group 2 (1.84 ± 0.25 vs. 1.05 ± 0.28, p < 0.0001). There was no difference in the average dose of phenylephrine used. DISCUSSION: Magnesium sulfate infusion initiated earlier in open fetal surgery reduces the total anesthetic exposure to the fetus.