Anchoring device to prevent membrane detachment and preterm premature rupture of membranes after fetal intervention.

OBJECTIVE: Anchoring the fetal membrane to the uterine wall via a novel suture delivery system could reduce the risk of preterm premature rupture of membranes (PPROM) after fetoscopic surgery. This study assesses the feasibility of using a novel device designed for minimally invasive suturing to anchor fetal membranes to the uterine wall and to close surgical defects after fetoscopy. METHODS: We tested the suturing device both ex vivo and in vivo. In the ex vivo studies, 12-French trocar defects were created with a fetoscope in five specimens of human uterine tissue with fetal membranes attached. Specimens were examined for integrity of the anchoring stitch. For in vivo studies, trocar defects were created in the two uterine horns of three pregnant ewes, each carrying twins at ~79-90 days gestation. One trocar defect in each ewe was repaired using the suture device, and the other was left unrepaired as a control. The repair sites were examined for membrane anchoring integrity when the defect was created and at delivery. RESULTS: Fetal membranes were successfully anchored to the uterine myometrium using this device in all five trials performed ex vivo. The in vivo trials also revealed successful membrane anchoring compared with controls both at the time of device deployment and five-to-eight weeks after the procedure. CONCLUSIONS: We successfully anchored amniotic membranes to the underlying myometrium via suturing device both ex vivo and in vivo. Further studies are needed to evaluate the efficacy of the device and to determine whether it can successfully anchor fetal membranes percutaneously in human subjects. This article is protected by copyright. All rights reserved.

Effect of intra-amniotic fluid pressure from polyhydramnios on cervical length in patients with twin-twin transfusion syndrome undergoing fetoscopic laser surgery.

OBJECTIVES: To determine the relationship between intra-amniotic pressure and cervical length (CL) in patients with twin-twin transfusion syndrome (TTTS) undergoing fetoscopic laser photocoagulation (FLP), and to identify pre- or intraoperative factors associated with increased intra-amniotic pressure in this population. METHODS: This was a prospective cohort study of patients undergoing FLP for TTTS. Exclusion criteria were triplet or higher-order gestation and prior cervical cerclage, amnioreduction or FLP procedure. CL was assessed using preprocedure transvaginal ultrasound. Intra-amniotic pressure measurements were obtained on initial placement of the trocar into the amniotic cavity, using a direct hydrostatic pressure gauge. The relationship between intra-amniotic pressure and CL was assessed using multivariate linear regression analysis, including relevant preoperative and intraoperative variables. RESULTS: In total, 283 pregnancies met the inclusion criteria. Quintero stage of TTTS was I in 33 pregnancies, II in 88, III in 150 and IV in 12. Mean gestational age (GA) at FLP was 20.7 ± 3 weeks. Mean intra-amniotic pressure was 23.1 ± 9 mmHg. On unadjusted linear regression analysis, there was no significant association between intra-amniotic pressure and preoperative CL (P = 0.24) or GA at delivery (P = 0.22). On multivariate analysis, the factors associated significantly with intra-amniotic pressure were: number of prior term deliveries (P = 0.03), recipient maximum vertical pocket (P < 0.0001), Quintero stage IV (P = 0.01) and type of anesthesia (sedation vs general anesthesia; P = 0.01). CONCLUSION: In pregnancies with TTTS, intra-amniotic pressure is not associated with CL or GA at delivery. This novel finding suggests that cervical shortening in this population is not mechanically driven. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Preterm prelabor rupture of membranes after fetoscopic laser surgery for twin-twin transfusion syndrome.

OBJECTIVE: To assess the incidence, clinical course, risk factors and outcomes of preterm prelabor rupture of membranes (PPROM) after fetoscopic laser surgery (FLS) for twin-twin transfusion syndrome (TTTS). METHODS: This was a prospective observational cohort study of 154 consecutive cases of TTTS. PPROM was defined as rupture of membranes before 34 weeks' gestation. Procedure-to-PPROM and PPROM-to-delivery intervals were determined. Relevant preoperative and intraoperative variables were analyzed by univariate and multivariate logistic regression to determine their impact on PPROM after FLS. RESULTS: The incidence of PPROM was 39% (n = 60), occurring at a mean gestational age of 27.2 ± 4.6 weeks. Median procedure-to-PPROM interval was 46 (range, 1-105; interquartile range (IQR), 13-66) days and median PPROM-to-delivery interval was 1 (range, 0-93; IQR, 0-13) day. Mean gestational age at delivery in cases with PPROM was 29.0 ± 4.5 weeks compared with 32.6 ± 3.9 weeks in cases without PPROM (P < 0.0001). Insertion of a collagen plug was the only significant factor found on both univariate and multivariate analysis to be associated with an increased rate of PPROM (odds ratio, 3.1 (95% CI, 1.2-8.0); P = 0.006). There was no statistically significant difference in fetal (P = 0.07) or neonatal (P = 0.08) survival between those with and those without PPROM. CONCLUSIONS: PPROM after FLS increases prematurity by 3.6 weeks. The latency period after PPROM was 2 weeks; 50% of patients delivered within 24 h. No variable thought to be associated with PPROM after FLS was found to be significantly associated with this complication. Other etiologies and mechanisms for PPROM after FLS should be explored. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Preterm delivery after fetoscopic laser surgery for twin-twin transfusion syndrome: etiology and risk factors.

OBJECTIVE: Preterm delivery after fetoscopic laser surgery (FLS) for twin-twin transfusion syndrome (TTTS) is a major complication. The causative factors leading to preterm delivery continue to be elusive and a better understanding of the risk factors could reduce complications. The objective of this study was to determine the etiology of preterm delivery after FLS for TTTS and its associated risk factors. METHODS: This was a secondary analysis of a prospective study of 203 patients with TTTS who underwent FLS at a single center between September 2011 and December 2014. Preoperative, operative, postoperative, delivery and neonatal data were reviewed. Preterm delivery was categorized according to etiology into three groups: spontaneous (SPT), indicated (IND) and elective (ELC). Comparisons between groups were performed by ANOVA. Kaplan-Meier survival analysis was performed to compare the procedure-to-delivery interval between groups. To identify risk factors for preterm delivery, logistic regression, with calculation of relative risks (RR), was performed, with P < 0.05 considered statistically significant. RESULTS: Mean gestational age at time of FLS was 20.6 ± 2.4 weeks and mean gestational age at delivery was 30.9 ± 4.7 weeks. Iatrogenic preterm prelabor rupture of membranes (iPPROM) occurred in 39% of cases. SPT preterm delivery occurred in 97 (48%) patients, IND preterm delivery in 65 (32%) and ELC preterm delivery in 41 (20%). In the IND group, 30 (46%) patients delivered for fetal indications, 31 (48%) for maternal indications and four (6%) for combined fetal and maternal indications. The overall chorioamnionitis rate was 6.4%; of these, nine (9%) were in the SPT group and four (6%) were in the IND group, with no case occurring in the ELC group. There was a significant difference in procedure-to-delivery interval between groups (P < 0.0001). Using variables from the ELC group as a baseline, significant risk factors for SPT preterm delivery were iPPROM (RR, 16.2 (95% CI, 4.5-57.7)), preoperative cervical length (RR, 0.96 (95% CI, 0.92-0.998)) and number of anastomoses (RR, 1.14 (95% CI, 1.02-1.27)). Significant risk factors for IND preterm delivery were iPPROM (RR, 9.6 (95% CI, 2.6-35.0)) and number of ablated anastomoses (RR, 1.13 (95% CI, 1.02-1.30)). CONCLUSION: iPPROM and an increased number of ablated placental anastomoses were associated independently with SPT and IND preterm deliveries. A shorter preoperative cervical length was associated with SPT preterm delivery. Strategies to prevent iPPROM and for management of cervical length shortening are needed urgently in these pregnancies. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Cryopreserved human umbilical cord patch for in-utero spina bifida repair.

OBJECTIVE: To identify a patch system to repair surgically created spina bifida in a sheep model for its efficacy in healing the skin defect, protecting the underlying spinal cord and reducing the Chiari II malformation. METHODS: Spina bifida was created surgically in 16 fetuses from eight timed-pregnant sheep at gestational age of 75 days. Two fetuses did not survive the procedure. Repeat hysterotomy was performed at 95 days' gestation to cover the defect with either biocellulose film with underwater adhesive (BCF-adhesive) (n = 7) or human umbilical cord with suture (HUC-suture) (n = 7). Three fetuses without formation of the defect served as reference controls. The skin healing was examined by direct visualization after a planned Cesarean section at term, followed by histological analysis using hematoxylin and eosin and Masson's trichrome stains. Mid-sagittal sections of the fetal cranium and upper cervical spine were analyzed by a pediatric neuroradiologist who was blinded to the type of patch received. RESULTS: Three fetuses that received the BCF-adhesive and six fetuses that received the HUC-suture survived to term for final analysis. As a result of dislodgment of the BCF-adhesive, all spina bifida defects repaired using BCF-adhesive were not healed and showed exposed spinal cord with leakage of cerebrospinal fluid. In contrast, all spinal defects repaired by HUC-suture were healed with complete regrowth of epidermal, dermal and subdermal tissue components, with no exposed spinal cord. The maximal skin wound width was 21 ± 3.6 mm in the BCF-adhesive group but 3 ± 0.8 mm in the HUC-suture group (P < 0.001). The spinal cord area (P = 0.001) and the number of anterior horn cells (P = 0.03) was preserved to a greater degree in the HUC-suture group than in the BCF-adhesive group, whilst psammoma bodies, signifying neuronal degeneration, were only observed in the BCF-adhesive group. Anatomic changes, indicative of Chiari II malformation, were seen in all three fetuses of the BCF-adhesive group but in none of the HUC-suture group (P < 0.01). CONCLUSION: Cryopreserved umbilical cord graft is a promising regenerative patch for intrauterine repair of spina bifida.

Cryopreserved human amniotic membrane and a bioinspired underwater adhesive to seal and promote healing of iatrogenic fetal membrane defect sites.

INTRODUCTION: We investigated the ability of cryopreserved human amniotic membrane (hAM) scaffold sealed with an underwater adhesive, bio-inspired by marine sandcastle worms to promote healing of iatrogenic fetal membrane defects in a pregnant swine model. METHODS: Twelve Yucatan miniature pigs underwent laparotomy under general anesthesia at 70 days gestation (term = 114 days). The gestational sacs were assigned to uninstrumented (n = 24) and instrumented with 12 Fr trocar, which was further randomized into four different arms-no hAM patch, (n = 22), hAM patch secured with suture (n = 16), hAM patch with no suture (n = 14), and hAM patch secured with adhesive (n = 9). The animals were euthanized 20 days after the procedure. Gross and histological examination of the entry site was performed for fetal membrane healing. RESULTS: There were no differences in fetal survival, amniotic fluid levels, or dye-leakage from the amniotic cavity between the groups. The fetal membranes spontaneously healed in instrumented sacs without hAM patches. In sacs with hAM patches secured with sutures, the patch was incorporated into the swine fetal membranes. In sacs with hAM patches without sutures, 100% of the patches were displaced from the defect site, whereas in sacs with hAM patches secured with adhesive 55% of the patches remained in place and showed complete healing (p = 0.04). DISCUSSION: In contrast to humans, swine fetal membranes heal spontaneously after an iatrogenic injury and thus not an adequate model. hAM patches became incorporated into the defect site by cellular ingrowth from the fetal membranes. The bioinspired adhesive adhered the hAM patches within the defect site.

Cervical length in prediction of preterm birth after laser surgery for twin-twin transfusion syndrome.

OBJECTIVES: To determine the risk factors for spontaneous preterm delivery (PTD) or preterm prelabor rupture of membranes (PPROM) at < 34 weeks' gestation after fetoscopic laser surgery for twin-twin transfusion syndrome and to identify the optimal threshold for preoperative cervical length (CL) that indicates a high risk for spontaneous PTD. METHODS: This was a secondary analysis of data prospectively collected from 449 patients at three fetal centers. CL measurements were obtained by preoperative transvaginal ultrasound, at a gestational age of 16-26 weeks. The risk factors associated with spontaneous PTD before 34 weeks' gestation were determined using multivariable logistic regression analysis. We excluded patients with dual fetal demise and those with maternal or fetal indications for delivery without PPROM (n = 63). The optimal threshold for cervical length to predict spontaneous PTD before 34 weeks was determined using a receiver-operating characteristics (ROC) curve and Youden index. Additionally, the CL threshold for spontaneous PTD at 2-week intervals between 24 and 34 weeks was determined. RESULTS: Spontaneous PTD before 34 weeks occurred in 206 (53.4%) of the included patients. Only the preoperative CL was significantly associated with spontaneous PTD. The preoperative CL was normally distributed with a mean of 37.6 ± 10.3 mm (range, 5-66 mm). Maternal age and parity were positively associated, and gestational age at procedure and anterior placenta were negatively associated, with CL on multivariable linear regression analysis. The area under the ROC curve for predicting spontaneous PTD with CL measurements was 0.61 (P = 0.02) and the optimal threshold was 28 mm with a Youden index of 0.19 (sensitivity and specificity of 92% and 27%, respectively). A CL measurement of < 28 mm increased the risk of spontaneous PTD for all gestational age thresholds. CONCLUSIONS: Spontaneous PTD at < 34 weeks' gestation is associated with a preoperative CL of < 28 mm. Preventive strategies should focus on this high-risk group.

Risk factors associated with preterm delivery after fetoscopic laser ablation for twin-twin transfusion syndrome.

OBJECTIVE: Despite improved perinatal survival following fetoscopic laser ablation (FLA) for twin-twin transfusion syndrome (TTTS), prematurity remains an important contributor to perinatal mortality and morbidity. The objective of the study was to identify risk factors for complicated preterm delivery after FLA. METHODS: Retrospective cohort study of prospectively collected data on maternal/fetal demographics and pre-operative, operative and postoperative variables of 459 patients treated with FLA in three USA fetal centers. Multivariate linear regression was performed to identify significant risk factors associated with preterm delivery, which were cross-validated using the k-fold method. Multivariate logistic regression was performed to identify risk factors for early compared with late preterm delivery based on median gestational age at delivery of 32 weeks. RESULTS: There were significant differences in case selection and outcomes between the centers. After controlling for the center of surgery, multivariate analysis indicated that a lower maternal age at procedure, a history of previous prematurity, shortened cervical length, use of amnioinfusion, a cannula diameter of 12 French (Fr), lack of a collagen plug placement and iatrogenic preterm premature rupture of membranes (iPPROM) were significantly associated with a lower gestational age at delivery. CONCLUSIONS: Specific fetal/maternal and operative variables are associated with preterm delivery after FLA for the treatment of TTTS. Further studies to modify some of these variables may decrease the perinatal morbidity after laser therapy.

Absorbable gelatin plug does not prevent iatrogenic preterm premature rupture of membranes after fetoscopic laser surgery for twin-twin transfusion syndrome.

OBJECTIVE: Despite fetoscopic laser ablation (FLA) having emerged as an effective treatment for twin-twin transfusion syndrome (TTTS), major postintervention challenges, such as iatrogenic preterm premature rupture of membranes (iPPROM), remain. A chorioamniotic plug (CAP) made of absorbable gelatin sponge has been used to seal the trocar entry site in the chorioamniotic layers to promote healing and prevent iPPROM, yet the results have been equivocal. Our objective was to test the hypothesis that, following FLA for TTTS, iPPROM may be prevented by placement of an absorbable gelatin CAP. METHODS: A retrospective cohort study was performed on prospectively collected data from 134 consecutive patients who underwent FLA for TTTS. The decision for CAP placement was at the discretion of the physician. Preoperative, operative and postoperative variables were collected and analyzed. The primary outcome was the incidence of iPPROM, and the secondary outcomes were procedure-to-delivery interval and gestational age at delivery. Comparative statistical analysis was performed as appropriate. RESULTS: A CAP was placed in 72 (54%) of 134 patients. Factors significantly associated with CAP placement were higher gravidity (P = 0.03), anterior placentation (P = 0.04), general endotracheal intubation (P = 0.02) and a cannula diameter of 12-Fr (P = 0.003). There were no differences between CAP and no-CAP groups in the rate of iPPROM (39% vs 34%, respectively; P = 0.42) or in the procedure-to-delivery interval (65.3 ± 34.7 days vs 58.2 ± 30.8 days, respectively; P = 0.21). The gestational age at delivery was later in the CAP group compared with the no-CAP group (30.7 ± 4.5 weeks vs 28.9 ± 3.9 weeks, respectively; P = 0.02). CONCLUSIONS: CAP did not reduce the overall risk for iPPROM and did not increase the procedure-to-delivery interval. Further research is needed to identify other methods to prevent iPPROM and prolong pregnancy after laser therapy.

Changes in soil quality and below-ground carbon storage with conversion of traditional agricultural crop lands to bioenergy crop production.

Berm-isolated (0.5 ha) plots have been used since 1995 to quantify changes in soil and water quality with conversion from agricultural to bioenergy crops. Soil quality improvements, including increases in soil carbon storage, have occurred on sites planted to woody or herbaceous species, and no-till corn compared with tilled corn or cotton. Initial increases in soil carbon occurred within the upper 10 cm of the soil profile. Soil carbon on plantings of switchgrass, no-till corn, and sweetgum with a cover crop between the rows increased over the first 3 years. Soil carbon decreased by 6% on the sweetgum plantings without a cover crop and remained lower through the fifth growing season. Overall, the greatest increases in below ground carbon storage have occurred primarily within the upper 40 cm. Former land use, growth characteristics, management practices, and soil characteristics appear to be the primary factors determining the timing, depth. and extent of changes in soil carbon storage for bioenergy and no-till crops.