Continuous Fetal Cardiac Monitoring during Fetoscopic Myelomeningocele Repair and Relationship to Spectral Doppler Changes.

INTRODUCTION: No evidence-based protocols exist for fetal cardiac monitoring during fetoscopic myelomeningocele (fMMC) repair and intraprocedural spectral Doppler data are limited. We determined the feasibility of continuous fetal echocardiography during fMMC repair and correlated Doppler changes with qualitative fetal cardiac function during each phase of fMMC repair. METHODS: Patients undergoing fMMC repair had continuous fetal echocardiography interpreted in real-time by pediatric cardiology. Fetal data included fetal heart rate (FHR), qualitative cardiac function, mitral and tricuspid valve inflow waveforms, and umbilical artery (UA), umbilical vein (UV), ductus arteriosus (DA), and ductus venosus (DV) Dopplers. RESULTS: UA abnormalities were noted in 14/25 patients, UV abnormalities were observed in 2 patients, and DV and DA abnormalities were each noted in 4 patients. Qualitative cardiac function was normal for all patients with the exception of one with isolated left ventricular dysfunction during myofascial flap creation, concurrent with an abnormal UA flow pattern. All abnormalities resolved by the first postoperative day. CONCLUSIONS: Continuous fetal echocardiography was feasible during all fMMC repairs. Spectral Doppler changes in the UA were common during fMMC procedures but qualitative cardiac dysfunction was rare. Abnormalities in the UV, DV, and DA Dopplers, FHR, and cardiac function were less common findings.

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.

Assessment of evidence underlying guidelines by the Society for Maternal-Fetal Medicine.

BACKGROUND: The Society for Maternal-Fetal Medicine, sometimes together with the American College of Obstetricians and Gynecologists, publishes guidelines utilizing the Grading of Recommendations, Assessment, Development, and Evaluation system to rate the quality of evidence and assign the strength of its recommendations. The strength of recommendations is determined by the quality of evidence and 3 other strength determinants that are defined in this system. OBJECTIVE: This study aimed to assess all recommendations by the Society for Maternal-Fetal Medicine assessed by the Grading of Recommendations, Assessment, Development, and Evaluation system, determine the quality of evidence supporting them, evaluate the relationship between quality of evidence and strength of recommendations, and determine the extent to which the other 3 strength determinants were employed to assign recommendation strength. STUDY DESIGN: All publications from the Society for Maternal-Fetal Medicine Publications and Guidelines website were reviewed, but only the ones with Grading of Recommendations, Assessment, Development, and Evaluation recommendations were analyzed. These were aggregated by their rating for quality of evidence and strength. Quality and strength were first compared across all recommendations. Subsequently, they were compared with stratification by recommendation topic and type (eg, interventions, counseling, screening, and diagnosis). References supporting each recommendation were also summarized by type (eg, randomized trial, retrospective study). The quality of evidence for each recommendation was then compared with the supporting reference types. Other characteristics that may contribute to strength were also evaluated. Finally, we compared recommendations authored jointly by the Society for Maternal-Fetal Medicine and the American College of Obstetricians and Gynecologists with those by the Society for Maternal-Fetal Medicine alone. RESULTS: The Society for Maternal-Fetal Medicine published 24 documents containing 235 recommendations assessed by the Grading of Recommendations, Assessment, Development, and Evaluation system. There were 35 (15%) recommendations supported by high-quality evidence; 34 (97%) were determined to be strong. Recommendations supported by moderate-quality (n=102) and low-quality (n=75) evidence were also rated as strong in 78% and 68% of cases, respectively. Recommendations were supported by randomized trials 8% of the time and references that summarize primary data (eg, meta-analyses, reviews, previous guidelines) 64% of the time. Recommendations with higher quality evidence ratings were more likely to be supported by references that summarize primary data (69% high-quality, 74% moderate-quality, 49% low-quality). Topics with recommendations authored jointly by the Society for Maternal-Fetal Medicine and the American College of Obstetricians and Gynecologists were supported by higher quality evidence than those by the Society for Maternal-Fetal Medicine alone (high quality, 26% vs 9%, respectively). CONCLUSION: Recommendations by the Society for Maternal-Fetal Medicine assessed by the Grading of Recommendations, Assessment, Development, and Evaluation system were supported by high-quality evidence in 15% of cases. This suggests that well-designed, high-quality clinical trials remain a priority in obstetrics. Strong recommendations were often made on the basis of Grading of Recommendations, Assessment, Development, and Evaluation strength determinants other than quality of evidence. Increased transparency of the Society for Maternal-Fetal Medicine's determination of strong recommendations based on strength determinants other than quality of the evidence may be useful to practicing clinicians.

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.

Cervical Length as a Predictor of Preterm Delivery in an Unselected Cohort of Women with Twin Pregnancies.

OBJECTIVE: To determine the risk of spontaneous preterm delivery (SPTD) associated with transvaginal cervical length (TVCL) in an unselected cohort. STUDY DESIGN: This is a retrospective study of serial TVCLs in unselected twin gestations. Receiver operator curves for SPTD were constructed from TVCLs at 18, 20, 22, and 24 weeks. Prediction thresholds were determined using a false discovery rate of 10%. The risk of SPTD was compared with previously published, prospective data from a meta-analysis. RESULTS: A total of 1,228 women were included. SPTD occurred prior to 35 weeks in 232 (18.9%), 126 (10.3%), and 24 (2.0%) women prior to 35, 32, and 28 weeks. TVCL was most predictive at 22 weeks (area under the curve = 0.67). TVCL thresholds for predicting SPTD prior to 35, 32, and 28 weeks were 3.1, 3.0, and 2.9 cm. Compared with a previous meta-analysis, the risk of SPTD < 34, 32, and 28 weeks was lower (positive likelihood ratio 9.0 vs. 5.4, 10.1 vs. 5.9, and 9.6 vs. 4.3). CONCLUSION: TVCL is modestly predictive of SPTD in twin gestations. Compared with previous prospective studies, this cohort has lower risk of SPTD at similar TVCLs.

Association between change in cervical length and spontaneous preterm birth in twin pregnancies.

BACKGROUND: There is a lack of consensus on the optimal transvaginal cervical length for determining risk for spontaneous preterm birth in twin pregnancies. Change in transvaginal cervical length over time may reflect early activation of the parturition process, as has been demonstrated in singleton pregnancies. The association between change in transvaginal cervical length and the risk for spontaneous preterm birth has not yet been described in the population of women with diamniotic twin pregnancies. OBJECTIVE: Our primary objective is to determine whether rate of change in transvaginal cervical length in the midtrimester is associated with spontaneous preterm birth in twin gestations. Our secondary objective is to describe parameters for identifying patients at increased risk for spontaneous preterm birth based on change in transvaginal cervical length over time. STUDY DESIGN: This is a retrospective cohort of serial transvaginal cervical length performed for twin pregnancies at a single institution from 2008 through 2015. Women with diamniotic twin pregnancies who had transvaginal cervical length measurements at 18 and 22 weeks' gestation and outcome data available were included. Logistic regression was used to determine the relationship between the rate of change in transvaginal cervical length and the risk for the primary outcome of spontaneous preterm birth <35 weeks as well as spontaneous preterm birth <32 weeks. RESULTS: In all, 527 subjects met inclusion criteria for this study. The average rate of change in transvaginal cervical length for patients with spontaneous preterm birth <35 weeks was -0.21 cm/wk (SD 0.27) vs -0.10 cm/wk (SD 0.24) for patients who delivered ≥35 weeks (P < .01). The rate of change in transvaginal cervical length was associated with spontaneous preterm birth <35 weeks when controlling for initial transvaginal cervical length and other important risk factors for spontaneous preterm birth. Results for spontaneous preterm birth <32 weeks were similar. This association remained significant when the rate of weekly change was treated as a dichotomous variable based on an apparent inflection point in the risk for spontaneous preterm birth: women with rapid change in transvaginal cervical length, ≥-0.2 cm/wk, had 3.45 times the odds of spontaneous preterm birth as those with less rapid change (95% confidence interval, 2.15-5.52) when controlling for initial transvaginal cervical length. CONCLUSION: Change in transvaginal cervical length in the midtrimester is associated with spontaneous preterm birth, and therefore protocols for serial transvaginal cervical length measurement can provide the clinician with information to identify at-risk patients. A decrease of ≥0.2 cm/wk of transvaginal cervical length identifies patients at increased risk for spontaneous preterm birth <35 weeks.

Outcomes of Operative Vaginal Delivery during Trial of Labor after Cesarean Delivery.

Objective The objective of this study is to determine the maternal and neonatal morbidity associated with attempting operative vaginal delivery (OVD) compared with the alternative of a laboring repeat cesarean delivery (LRCD) in women attempting a trial of labor after cesarean delivery (TOLAC). Methods This is a secondary analysis of a multicenter prospective study designed to assess perinatal outcomes of OVD in women with a prior uterine scar. The study includes women who attempted TOLAC and reached +2 station with a fully dilated cervix. Composites on neonatal and maternal morbidity were compared between women in whom OVD was attempted and those who underwent LRCD by fitting multivariate logistic regression models. Results In total, 6,489 women attempting TOLAC reached 2+ station with a fully dilated cervix. Of these, 5,640 (86.9%) had a spontaneous vaginal delivery, 762 (11.7%) underwent attempted OVD, and 87 (1.3%) had an LRCD. Compared with attempting OVD, LRCD was associated with greater neonatal morbidity (odds ratio [OR]: 2.41; 95% confidence interval [CI]: 1.13-5.15) and less maternal morbidity (OR: 0.28; 95% CI: 0.14-0.55). Maternal morbidity of OVD is driven by perineal injury. Conclusion In laboring women with a previous uterine scar, attempting OVD is associated with greater maternal and less neonatal morbidity than LRCD.

A new paradigm for the role of smooth muscle cells in the human cervix.

BACKGROUND: Premature cervical remodeling resulting in spontaneous preterm birth may begin with premature failure or relaxation at the internal os (termed "funneling"). To date, we do not understand why the internal os fails or why funneling occurs in some cases of premature cervical remodeling. Although the human cervix is thought to be mostly collagen with minimal cellular content, cervical smooth muscle cells are present in the cervix and can cause cervical tissue contractility. OBJECTIVE: To understand why the internal os relaxes or why funneling occurs in some cases of premature cervical remodeling, we sought to evaluate cervical smooth muscle cell content and distribution throughout human cervix and correlate if cervical smooth muscle organization influences regional cervical tissue contractility. STUDY DESIGN: Using institutional review board-approved protocols, nonpregnant women <50 years old undergoing hysterectomy for benign indications were consented. Cervical tissue from the internal and external os were immunostained for smooth muscle cell markers (α-smooth muscle actin, smooth muscle protein 22 calponin) and contraction-associated proteins (connexin 43, cyclooxygenase-2, oxytocin receptor). To evaluate cervical smooth muscle cell morphology throughout the entire cervix, whole cervical slices were obtained from the internal os, midcervix, and external os and immunostained with smooth muscle actin. To correlate tissue structure with function, whole slices from the internal and external os were stimulated to contract with 1 µmol/L of oxytocin in organ baths. In separate samples, we tested if the cervix responds to a common tocolytic, nifedipine. Cervical slices from the internal os were treated with oxytocin alone or oxytocin + increasing doses of nifedipine to generate a dose response and half maximal inhibitory concentration. Student t test was used where appropriate. RESULTS: Cervical tissue was collected from 41 women. Immunohistochemistry showed cervical smooth muscle cells at the internal and external os expressed mature smooth muscle cell markers and contraction-associated proteins. The cervix exhibited a gradient of cervical smooth muscle cells. The area of the internal os contained 50-60% cervical smooth muscle cells that were circumferentially organized in the periphery of the stroma, which may resemble a sphincter-like pattern. The external os contained approximately 10% cervical smooth muscle cells that were randomly scattered in the tissue. In organ bath studies, oxytocin stimulated the internal os to contract with more than double the force of the external os (1341 ± 693 vs 523 ± 536 integrated grams × seconds, respectively, P = .009). Nifedipine significantly decreased cervical tissue muscle force compared to timed vehicle control (oxytocin alone) at doses of 10(-5) mol/L (vehicle 47% ± 15% vs oxytocin + nifedipine 24% ± 16%, P = .007), 10(-4) mol/L (vehicle 46% ± 16% vs oxytocin + nifedipine -4% ± 20%, P = .003), and 10(-3) mol/L (vehicle 42% ± 14% vs oxytocin + nifedipine -15% ± 18%, P = .0006). The half maximal inhibitory concentration for nifedipine was 1.35 × 10(-5) mol/L. CONCLUSION: Our findings suggest a new paradigm for cervical tissue morphology-one that includes the possibility of a specialized sphincter at the internal os. This new paradigm introduces novel avenues to further investigate potential mechanisms of normal and premature cervical remodeling.

Incidence, pathophysiology, and clinical manifestations of antiphospholipid syndrome.

Antiphospholipid syndrome (APLS) is a complex systemic disease with a wide variety of clinical manifestations. In the obstetric population, recurrent early pregnancy loss, fetal loss, and thrombosis are hallmarks of the disease. Patients with APLS have developed one or more pathogenic auto-antibodies directed against plasma and cell surface proteins. These antibodies are characterized by their affinity for anionic phospholipids. Interactions between APLS antibodies and their protein targets influence a wide variety of biological systems and signaling pathways, including monocytes, platelets, the complement system, and endothelial cells. While much research is currently directed at understanding the mechanisms involved in this autoimmune disease, the key clinical presentation is the hypercoagulable state resulting in thrombosis occurring in essentially any arterial or venous location, as well as numerous obstetrical complications. Treatment of APLS is generally directed at preventing thrombosis and poor pregnancy outcomes by ameliorating the hypercoagulable state.

The novel endocrine disruptor tolylfluanid impairs insulin signaling in primary rodent and human adipocytes through a reduction in insulin receptor substrate-1 levels.

Emerging data suggest that environmental endocrine disrupting chemicals may contribute to the pathophysiology of obesity and diabetes. In a prior work, the phenylsulfamide fungicide tolylfluanid (TF) was shown to augment adipocyte differentiation, yet its effects on mature adipocyte metabolism remain unknown. Because of the central role of adipose tissue in global energy regulation, the present study tested the hypothesis that TF modulates insulin action in primary rodent and human adipocytes. Alterations in insulin signaling in primary mammalian adipocytes were determined by the phosphorylation of Akt, a critical insulin signaling intermediate. Treatment of primary murine adipose tissue in vitro with 100nM TF for 48h markedly attenuated acute insulin-stimulated Akt phosphorylation in a strain- and species-independent fashion. Perigonadal, perirenal, and mesenteric fat were all sensitive to TF-induced insulin resistance. A similar TF-induced reduction in insulin-stimulated Akt phosphorylation was observed in primary human subcutaneous adipose tissue. TF treatment led to a potent and specific reduction in insulin receptor substrate-1 (IRS-1) mRNA and protein levels, a key upstream mediator of insulin's diverse metabolic effects. In contrast, insulin receptor-ß, phosphatidylinositol 3-kinase, and Akt expression were unchanged, indicating a specific abrogation of insulin signaling. Additionally, TF-treated adipocytes exhibited altered endocrine function with a reduction in both basal and insulin-stimulated leptin secretion. These studies demonstrate that TF induces cellular insulin resistance in primary murine and human adipocytes through a reduction of IRS-1 expression and protein stability, raising concern about the potential for this fungicide to disrupt metabolism and thereby contribute to the pathogenesis of diabetes.

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.

Twin reverse arterial perfusion: Timing of intervention.

Twin reverse arterial perfusion (TRAP) sequence is a severe anomaly in monochorionic twins where one twin has profound corporeal underdevelopment and acardia. The normal "pump" co-twin provides blood flow to the acardiac twin through placental anastomoses which may lead to cardiac failure and pump twin demise as well as preterm delivery from severe polyhydramnios. Treatments include radiofrequency ablation, bipolar cord coagulation, and intrafetal laser with each aimed at occluding blood flow to the acardiac twin. However, none of these modalities has proven superior in terms of either pump twin survival or minimization of complications, including preterm premature rupture of membranes, preterm birth, or unexpected co-twin demise. The optimal timing of treatment is also unknown, without clear indications for intervention versus expectant management. Very early treatment of TRAP (i.e., <16 weeks) has been proposed to reduce first-trimester demise; however, this approach remains experimental. Further investigation is required to determine the best treatment and timing of intervention for TRAP.

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.

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.

Placental Growth Factor and the Risk of Adverse Neonatal and Maternal Outcomes.

OBJECTIVE: To evaluate whether abnormal plasma placental growth factor (PlGF) level is associated with adverse neonatal and maternal outcomes. METHODS: This was a secondary analysis of the Preeclampsia Triage by Rapid Assay Trial (PETRA), a prospective, multicenter, observational study that enrolled women with suspected preeclampsia. Our analysis included women age 18-45 years with a singleton pregnancy between 20 and 41 weeks of gestation. Plasma collected at enrollment was used for PlGF measurement. Abnormal PlGF was defined as low (100 pg/mL or less) or very low (less than 12 pg/mL). The primary outcomes were composite adverse neonatal and maternal outcomes. We used multivariable Poisson regression models to examine the association between PlGF and outcomes. RESULTS: Of 1,112 women who met the inclusion criteria, plasma PlGF was low in 742 (67%) and very low in 353 (32%). In the cohort, the overall rates of the composite adverse neonatal and maternal outcomes were 6.4% and 4.8%, respectively. Compared with normal PlGF (more than 100 pg/mL), low PlGF was significantly associated with an increased risk of the composite neonatal outcome (9.2% vs 0.8%; adjusted relative risk [aRR] 17.2, 95% CI 5.2-56.3), and the composite maternal outcome (6.2% vs 1.9%; aRR 3.6, 95% CI 1.7-8.0). Very low PlGF was also significantly associated with both neonatal and maternal outcomes. The sensitivity and specificity of low PlGF were 95.8% and 35.3%, respectively, for the composite neonatal outcome, and 86.8% and 34.3% for the composite maternal outcome. Although the positive predictive values were low (9.2% and 6.2%, respectively), the negative predictive value of low PlGF for neonatal and maternal outcomes was 99.2% and 98.1%, respectively. CONCLUSION: Among women being evaluated for preeclampsia, those with abnormal PlGF are significantly more likely to experience adverse neonatal and maternal outcomes. These outcomes occur infrequently when the PlGF is normal. These findings suggest that PlGF may be useful for risk stratification of women with suspected preeclampsia. FUNDING SOURCE: No funding was received for this study. The original PETRA study was supported by funding from Alere.

Middle Cerebral Artery Doppler Velocimetry for the Diagnosis of Twin Anemia Polycythemia Sequence: A Systematic Review.

Twin anemia polycythemia sequence (TAPS) is a rare complication of monochorionic diamniotic (MCDA) twins. Middle cerebral artery peak systolic velocity (MCA-PSV) measurements are used to screen for TAPS while fetal or neonatal hemoglobin levels are required for definitive diagnosis. We sought to perform a systematic review of the efficacy of MCA-PSV in diagnosing TAPS. Search criteria were developed using relevant terms to query the Pubmed, Embase, and SCOPUS electronic databases. Publications reporting diagnostic characteristics of MCA-PSV measurements (i.e., sensitivity, specificity or receiver operator curves) were included. Each article was assessed for bias using the Quality Assessment of Diagnostic Accuracy Studies II (QUADAS II) tool. Results were assessed for uniformity to determine whether meta-analysis was feasible. Data were presented in tabular form. Among publications, five met the inclusion criteria. QUADAS II analysis revealed that four of the publications were highly likely to have bias in multiple areas. Meta-analysis was precluded by non-uniformity between definitions of TAPS by MCA-PSV and neonatal or fetal hemoglobin levels. High-quality prospective studies with consistent definitions and ultrasound surveillance protocols are still required to determine the efficacy of MCA-PSV in diagnosing TAPS. Other ultrasound findings (e.g., placenta echogenicity discordance) may augment Doppler studies.

Compliance with mechanical venous thromboproembolism prophylaxis after cesarean delivery.

OBJECTIVE: Universal perioperative mechanical thromboprophylaxis is recommended for patients undergoing cesarean delivery because of increased risk for venous thromboembolism (VTE) associated with this mode of delivery. While research supports clinical benefits from this approach, other specialties have demonstrated suboptimal compliance with prophylaxis device use. The objective of this study was to review patient compliance with sequential compression devices (SCDs). METHODS: This cross-sectional observational study utilized data from a prospective quality assurance analysis to evaluate demographic, medical and obstetrical factors associated with postoperative SCD compliance after cesarean delivery. Observations were performed before 7 a.m. on the first postoperative day, a time point when patients were unlikely to be fully ambulatory and would most benefit from device use. The reason for failure was documented in cases where the device was not being properly used. RESULTS: Two hundred and ninety-three patients underwent cesarean delivery, had SCD compliance assessed and were included in the analysis. Twenty one percent of patients (n=60) were non-compliant with SCD use. Reasons for noncompliance included patient discomfort, machine malfunction and incorrect device use. Patients who were non-compliant had similar risk factors for thromboembolism compared to women who were compliant. CONCLUSION: Although SCD's are effective in preventing thromboembolism, device use was suboptimal in this cohort of post-cesarean patients. These findings are similar to those from other fields. For institutions that rely primarily on mechanical thromboprophylaxis for obstetric patients, quality assurance and auditing of use may be necessary to ensure patients are receiving adequate prophylaxis. For post-cesarean patients with additional VTE risk factors, pharmacologic prophylaxis may be beneficial.

Glucocorticoid receptor ChIP-sequencing of subcutaneous fat reveals modulation of inflammatory pathways.

OBJECTIVE: To identify glucocorticoid receptor (GR)-associated chromatin sequences and target genes in primary human abdominal subcutaneous fat. METHODS: GR chromatin immunoprecipitation (ChIP)-sequencing (seq) methodology in subcutaneous human adipocytes treated ex vivo with dexamethasone (dex) was optimized to identify genome-wide dex-dependent GR-binding regions (GBRs). Gene expression analyses were performed in parallel ± dex treatment. RESULTS: Fat was obtained from four female surgical patients without obesity with a median age of 50.5 years. ChIP-seq analysis revealed 219 dex-associated GBRs. Of these, 136 GBRs were located within 100 kb of the transcriptional start site and associated with 123 genes. Combining these data with dex-induced gene expression, 70 of the 123 putative direct target genes were significantly up- or downregulated following 4 hours of dex treatment. Gene expression analysis demonstrated that the top 10 pathways reflected regulation of cellular metabolism and inflammation. DEPTOR, an inhibitor of mTOR, was identified as a potential direct GR target gene. CONCLUSIONS: This is the first report of genome-wide GR ChIP-seq and gene expression analysis in human fat. The results implicate regulation of key GR target genes that are involved in dampening inflammation and promoting cellular metabolism.