Randomized controlled trial of twin-twin transfusion syndrome laser surgery: the sequential trial.

BACKGROUND: Intraoperative blood transfer between twins during laser surgery for twin-twin transfusion syndrome can vary by surgical technique and has been proposed to explain differences in donor twin survival. OBJECTIVE: This trial compared donor twin survival with 2 laser techniques: the sequential technique, in which the arteriovenous communications from the volume-depleted donor to the volume-overloaded recipient are laser-occluded before those from recipient to donor, and the selective technique, in which the occlusion of the vascular communications is performed in no particular order. STUDY DESIGN: A single-center, open-label, randomized controlled trial was conducted in which twin-twin transfusion syndrome patients were randomized to sequential vs selective laser surgery. Nested within the trial, a second trial randomized patients with superficial anastomoses (arterioarterial and venovenous) to ablation of these connections first (before ablating the arteriovenous anastomoses) vs last. The primary outcome measure was donor twin survival at birth. RESULTS: A total of 642 patients were randomized. Overall donor twin survival was similar between the 2 groups (274 of 320 [85.6%] vs 271 of 322 [84.2%]; odds ratio, 1.12 [95% confidence interval, 0.73-1.73]; P=.605). Superficial anastomoses occurred in 177 of 642 cases (27.6%). Donor survival was lower in the superficial anastomosis group vs those with only arteriovenous communications (125 of 177 [70.6%] vs 420 of 465 [90.3%]; adjusted odds ratio, 0.33 [95% confidence interval, 0.20-0.54]; P<.001). In cases with superficial anastomoses, donor survival was independent of the timing of ablation or surgical technique. The postoperative mean middle cerebral artery peak systolic velocity was lower in the sequential vs selective group (1.00±0.30 vs 1.06±0.30 multiples of the median; P=.003). Post hoc analyses showed 2 factors that were associated with poor overall donor twin survival: the presence or absence of donor twin preoperative critical abnormal Doppler parameters and the presence or absence of arterioarterial anastomoses. Depending on these factors, 4 categories of patients resulted: (1) Category 1 (347 of 642 [54%]), no donor twin critical abnormal Doppler + no arterioarterial anastomoses: donor twin survival was 91.2% in the sequential and 93.8% in the selective groups; (2) Category 2 (143 of 642 [22%]), critical abnormal Doppler present + no arterioarterial anastomoses: donor survival was 89.9% vs 75.7%; (3) Category 3 (73 of 642 [11%]), no critical abnormal Doppler + arterioarterial anastomoses present: donor survival was 94.7% vs 74.3%; and (4) Category 4 (79 of 642 [12%]), critical abnormal Doppler present + arterioarterial anastomoses present: donor survival was 47.6% vs 64.9%. CONCLUSION: Donor twin survival did not differ between the sequential vs selective laser techniques and did not differ if superficial anastomoses were ablated first vs last. The donor twin's postoperative middle cerebral artery peak systolic velocity was improved with the sequential vs the selective approach. Post hoc analyses suggest that donor twin survival may be associated with the choice of laser technique according to high-risk factors. Further study is needed to determine whether using these categories to guide the choice of surgical technique will improve outcomes.

Percutaneous/mini-laparotomy fetoscopic repair of open spina bifida: a novel surgical technique.

Open spina bifida is the most common congenital anomaly of the central nervous system compatible with life. Prenatal repair of open spina bifida via open maternal-fetal surgery has been shown to improve postnatal neurologic outcomes, including reducing the need for ventriculoperitoneal shunting and improving lower neuromotor function. Fetoscopic repair of open spina bifida minimizes the maternal risks while providing similar neurosurgical outcomes to the fetus. The following 2 fetoscopic techniques are currently in use: (1) the laparotomy-assisted approach, and (2) the percutaneous approach. The laparotomy-assisted fetoscopic technique appears to be associated with a lesser risk of preterm birth than the percutaneous approach. However, the percutaneous approach avoids laparotomy and uterine exteriorization and is associated with lesser anesthesia risk and improved maternal postsurgical recovery. The purpose of this article was to describe our experience with a modified surgical approach, which we call percutaneous/mini-laparotomy fetoscopy, in which access to the uterus for one of the ports is done via a mini-laparotomy, whereas the other ports are inserted percutaneously. This technique draws on the benefits of both the laparotomy-assisted and the percutaneous techniques while minimizing their drawbacks. This surgical approach may prove invaluable in the prenatal repair of open spina bifida and other complex fetal surgical procedures.

Disinfection performance using a UV/persulfate system: effects derived from different aqueous matrices.

The development of advanced photochemical processes has experienced the emergence of a promising alternative for water disinfection, different from traditional methods. The applicability has primarily been investigated in drinking and wastewater; however, new challenges related to microbiological control in marine waters necessitate evaluating the applicability of this process in such water matrices. In this study, the efficacy of persulfate (PDS) activated with UV-light against E. faecalis has been tested on the bench scale. Firstly, optimization of the different PDS concentrations (1-10 mM) and exposure times (0-5 min) was performed in distilled water. 1 mM of PDS was selected as the best dosage within the range tested. Secondly, in order to evaluate the effects of different inorganic compounds usually found in natural waters, the efficiency of the UV/PDS system was tested in three different matrices: mineral water, saltwater, and marine saltwater. Finally, different bacteria were evaluated in consortium (E. coli + E. faecalis), suggesting the same inactivation level independently on the bacterial groups and structures. The results suggest that PDS is an attractive alternative to other photochemical processes currently in use for seawater treatment and this application deserved further research.

Risks of Preterm Premature Rupture of Membranes and Preterm Birth Post Fetoscopy Based on Location of Trocar Insertion Site.

OBJECTIVE: The objective of this study was to assess whether the location of the trocar insertion site for laser treatment of twin-twin transfusion syndrome was associated with preterm-premature rupture of membranes (PPROM) and preterm birth (PTB). STUDY DESIGN: In this study trocar location was documented in the operating room. Lower uterine segment (LUS) location was defined as any insertion <10 cm vertically from the pubic symphysis. Lateral location was defined as ≥5 cm horizontally from the midline. Patient characteristics were tested against three outcomes: PPROM ≤ 21 days postoperative, PTB < 28 weeks, and PTB < 32 weeks. For each outcome, multiple logistic models were fitted to examine the effect of trocar location, controlling for potential risk factors. RESULTS: A total of 743 patients were studied. Patients with LUS location were twice as likely as those with a more superior location to have PPROM ≤ 21 days (OR = 2.33, 1.12-4.83, p = 0.0236). Patients with both a LUS and Lateral location were over six times more likely to have PPROM ≤ 21 days (OR = 6.66, 2.36-18.78, p = 0.0003). Trocar insertion site was not associated with PTB. CONCLUSION: We found that trocar insertion in the LUS, particularly the lateral LUS, was associated with an increased risk of PPROM.

Risk factors for fetomaternal bleeding after laser therapy for twin-twin transfusion syndrome.

OBJECTIVE: To quantify and assess potential risk factors for transplacental passage of fetal red blood cells (RBCs) into the maternal circulation (fetomaternal bleeding, FMB) after laser surgery for twin-twin transfusion syndrome (TTTS). STUDY DESIGN: A retrospective study of Rhesus-D negative patients that underwent laser surgery for TTTS. Patients with and without postoperative detectable fetal RBCs on Kleihauer-Betke (KB) testing were compared to determine risk factors for FMB. Patients were further sub-classified into those with a FMB < 20% and ≥20% of estimated fetoplacental blood volume. RESULTS: Of 60 studied patients, 26/60 (43%) had a positive postoperative KB test. The median fetal:adult RBC ratio was 0.00125, estimated to be a FMB volume of 6.25 mL. There were 17/26 (65%) of patients with FMB < 20% and 9/26 (35%) patients with ≥20% of the fetoplacental blood volume. Stage III-Recipient and III-Recipient/Donor patients were more likely to have a positive KB test (14/21 [66.7%] vs 12/39 [30.8%], OR = 4.50 [1.27-16.54], P = 0.0162). No other risk factors for FMB were apparent. CONCLUSIONS: Fetomaternal bleed appears to be a common finding after laser surgery for TTTS. TTTS Stage, particularly stage III-Recipient and III-Recipient/Donor, appears to be a risk factor for FMB.

Endoscopic surgery for the antenatal treatment of myelomeningocele: the CECAM trial.

BACKGROUND: A recent randomized clinical trial named Management of Myelomeningocele Study (MOMS trial) showed that prenatal correction of open spina bifida (OSB) via open fetal surgery was associated with improved infant neurological outcomes relative to postnatal repair, but at the expense of increased maternal morbidity. OBJECTIVE: We sought to report the final results of our phase I trial (Cirurgia Endoscópica para Correção Antenatal da Meningomielocele [CECAM]) on the feasibility, safety, potential benefits, and side effects of the fetoscopic treatment of OSB using our unique surgical technique. STUDY DESIGN: Ten consecutive pregnancies with lumbosacral OSB were enrolled in the study. Surgeries were performed percutaneously under general anesthesia with 3 ports and partial carbon dioxide insufflation. After appropriate surgical positioning of the fetus, the neuroplacode was released with scissors and the skin was undermined to place a biocellulose patch over the lesion. The skin was closed over the patch using a single running stitch. Preoperative, postoperative, and postnatal magnetic resonance imaging were performed to assess hindbrain herniation. Neurodevelopmental evaluation was performed before discharge and at 3, 6, and 12 months. All cases were delivered by cesarean delivery, at which time the uterus was assessed for evidence of thinning or dehiscence. RESULTS: The median gestational age at the time of surgery was 27 weeks (range 25-28 weeks). Endoscopic repair was completed in 8 of 10 fetuses. Two cases were unsuccessful due to loss of uterine access. The mean gestational age at birth was 32.4 weeks with a mean latency of 5.6 weeks between surgery and delivery (range 2-8 weeks). There was 1 fetal and 1 neonatal demise, and 1 unsuccessful case underwent postnatal repair. Of the 7 infants available for analysis, complete reversal of hindbrain herniation occurred in 6 of 7 babies. Three babies required ventriculoperitoneal shunting or third ventriculostomy. Functional motor level was the same or better than the anatomical level in 6 of 7 cases. There was no significant maternal morbidity and no evidence of myometrial thinning or dehiscence. However, surgeries were complicated by premature rupture of membrane and prematurity. CONCLUSION: Our study suggests that the antenatal treatment of OSB using a fetoscopic approach and our unique surgical technique can result in a watertight seal, reversal of the hindbrain herniation, and better than expected motor function. Our technique differs substantially from the classic repair of OSB used in prior open fetal surgery and fetoscopic studies, in which the dura mater is dissected and the defect is closed in multiple layers. Instead, we use a biocellulose patch placed over the lesion and simple closure of the skin. As such, our technique is an alternative to the current paradigms in the antenatal treatment of OSB. Our clinical outcomes are in line with the results of our extensive prior animal work. Maternal benefits of our approach and technique include minimal morbidity and no myometrial legacy. Current limitations of the approach include potential loss of access, premature rupture of membranes, and attendant prematurity. Phase II trials are needed to prevent these complications and to further assess the risks and benefits of our distinct surgical approach and technique.

Twin-to-Twin Transfusion Syndrome: Definition, Staging, and Ultrasound Assessment.

OBJECTIVE: The purpose of this article is to review the definition of twin-to-twin transfusion syndrome (TTTS) and the sonographic diagnostic assessment of these cases prior to therapy. MATERIALS AND METHODS: The article addresses the terminology used to refer to the condition and describes the systematic ultrasound assessment of the condition, including the ultrasound diagnosis, the staging of the disease, cervical assessment and pre-operative mapping. RESULTS: From an etymologic and medical point of view, the term 'fetofetal transfusion' is more appropriate than 'TTTS'. However, as the latter, and its attendant acronym TTTS, have been widely adopted in the English language, it is impractical to change at this point. TTTS is defined sonographically in the combined presence of a maximum vertical pocket (MVP) of 8 cm or greater in one sac and 2 cm or less in the other sac, regardless of the gestational age at diagnosis. Staging of the condition using the Quintero staging system is practical, reproducible, and accepted. Transvaginal cervical length assessment should be an integral part of the ultrasound evaluation. Pre-operative mapping to anticipate the location of the placental vascular anastomoses and avoid injuring the dividing membrane is also discussed. CONCLUSIONS: The term 'TTTS' can continue to be used in the English medical literature. The condition can be diagnosed and assessed following a systematic ultrasound methodology. The use of such ultrasound methodology breaks the examination into a distinct set of components, assuring a comprehensive examination and proper communication among caregivers.

Laser Treatment of Twin-to-Twin Transfusion Syndrome.

OBJECTIVE: Laser ablation of all placental vascular anastomoses is the optimal treatment for twin-twin transfusion syndrome (TTTS). However, two important controversies are apparent in the literature: (a) a gap between concept and performance, and (b) controversy regarding whether all the anastomoses can be identified endoscopically and whether blind lasering of healthy placenta is justified. The purpose of this article is: (a) to address the potential source of the gap between concept and performance by analyzing the fundamental steps needed to successfully accomplish the surgery, and (b) to discuss the resulting competency benchmarks reported with the different surgical techniques. MATERIALS AND METHODS: Laser surgery for TTTS can be broken down into two fundamental steps: (1) endoscopic identification of the placental vascular anastomoses, (2) laser ablation of the anastomoses. The two steps are not synonymous: (a) regarding the endoscopic identification of the anastomoses, the non-selective technique is based upon lasering all vessels crossing the dividing membrane, whether anastomotic or not. The selective technique identifies and lasers only placental vascular anastomoses. The Solomon technique is based on the theory that not all anastomoses are endoscopically visible and thus involves lasering healthy areas of the placenta between lasered anastomoses, (b) regarding the actual laser ablation of the anastomoses, successful completion of the surgery (i.e., lasering all the anastomoses) can be measured by the rate of persistent or reverse TTTS (PRTTTS) and how often a selective technique can be achieved. Articles representing the different techniques are discussed. RESULTS: The non-selective technique is associated with the lowest double survival rate (35%), compared with 60-75% of the Solomon or the Quintero selective techniques. The Solomon technique is associated with a 20% rate of residual patent placental vascular anastomoses, compared to 3.5-5% for the selective technique (p < .05). Both the Solomon and the selective technique are associated with a 1% risk of PRTTTS. Adequate placental assessment is highest with the selective technique (99%) compared with the Solomon (80%) or the 'standard' (60%) techniques (p < .05). A surgical performance index is proposed. CONCLUSION: The Quintero selective technique was associated with the highest rate of successful ablation and lowest rate of PRTTTS. The Solomon technique represents a historical backward movement in the identification of placental vascular anastomoses and is associated with higher rate of residual patent vascular communications. The reported outcomes of the Quintero selective technique do not lend support to the existence of invisible anastomoses or justify lasering healthy placental tissue.

Decreased Total Placental Mass Found in Twin-Twin Transfusion Syndrome Gestations with Selective Growth Restriction.

INTRODUCTION: We examined placental weight characteristics associated with donor selective intrauterine growth restriction (SIUGR) among patients with twin-twin transfusion syndrome (TTTS) who underwent laser surgery. MATERIALS AND METHODS: Fresh placental specimens were studied. Pregnancies with higher-order multiples, fetal demise, or disrupted or nonsubmitted placental specimens were excluded. Placental characteristics prospectively collected included total placental weight, individual placental weight, and placental share. Data were compared between pregnancies with SIUGR (TTTS + SIUGR group) and those without SIUGR (TTTS-only group). RESULTS: Of 369 consecutive patients who underwent laser surgery for TTTS, 155 (42%) met inclusion criteria: 91 with TTTS + SIUGR and 64 with TTTS-only. Compared to the TTTS-only group, patients in the TTTS + SIUGR group had a lower total placental weight (608 ± 163 vs. 687 ± 224 g, p = 0.012), with a lower donor individual placental weight (237 ± 91 vs. 291 ± 124 g, p = 0.002), but no apparent difference in the individual placental weight of recipient twins (371 ± 109 vs. 396 ± 133 g, p = 0.211). Donor placental share was smaller in those pregnancies affected by SIUGR (38.7 ± 9.6 vs. 42.3 ± 9.8%, p = 0.029). DISCUSSION: TTTS patients with SIUGR had a lower total placental weight and a lower donor individual placental weight compared to those without SIUGR. These findings suggest that differences in donor individual placental weights for SIUGR gestations may not solely be related to differences in placental share.

Selective Reduction Using Intravascular Potassium Chloride Injection after Laser Surgery for Twin-Twin Transfusion Syndrome.

Selective reduction (SR) via intravascular potassium chloride (KCl) injection is contraindicated in monochorionic twins due to the presence of placental vascular communications, which may serve as a conduit for inter-twin passage of KCl or allow exsanguination of the living twin into the demised twin. After successful selective laser photocoagulation of communicating vessels (SLPCV) for twin-twin transfusion syndrome (TTTS), the twins' circulatory systems are rendered independent. Theoretically, intravascular KCl injection into one twin after successful SLPCV should not result in passage of the feticidal agent nor cause hemodynamic alterations in the co-twin. We describe 3 cases of 1,069 patients (0.3%) that underwent SLPCV for TTTS between 2003 and 2013 and subsequent SR. SLPCV was successfully completed at 180, 226, and 230 weeks' gestational age for Quintero stages III, IV, and III TTTS, respectively. SR via intravascular KCl injection was later performed at maternal request due to the risk of neurological compromise in one twin at 226, 254, and 236 weeks' gestational age. All co-twins survived after SR, and no neurological sequelae were suspected after birth. Further study is necessary before SR can be routinely considered after laser surgery for TTTS.

Abnormal umbilical artery Doppler findings in the recipient twin before laser surgery for twin-twin transfusion syndrome.

OBJECTIVES: In twin-twin transfusion syndrome (TTTS), persistent absent or reversed end-diastolic flow in the umbilical artery is a rare finding in the recipient twin, and the clinical implications of this finding are not well characterized. We sought to study the clinical importance of abnormal umbilical artery Doppler waveforms in recipient twins and determine the perinatal survival of these twins after laser surgery. METHODS: A retrospective study of patients with TTTS treated with laser surgery between 2006 and 2012 was conducted. Recipient twins with absent or reversed umbilical artery end-diastolic flow on preoperative sonography were identified, and clinical and perinatal outcomes were compared to the remaining cohort. Statistical analyses were performed with Fisher exact and χ(2) tests. RESULTS: Of 369 consecutive TTTS cases, 14 (3.8%) had absent or reversed umbilical artery end-diastolic flow in the recipient twin. The rate of hydrops was higher in this group compared to those without absent or reversed flow (35.7% [5 of 14] versus 10.1% [36 of 355]; P = .0125). The rate of recipient twin growth restriction was also higher in the absent or reversed flow group (28.6% [4 of 14] versus 3.9% [14 of 355]; P = .0029). There was an increased rate of recipient fetal demise within 24 hours after surgery in those with absent or reversed flow (21.4% [3 of 14] versus 2.5% [9 of 355]; P = .0078), although there was no statistical difference in 30-day survival between the groups (78.6% [11 of 14] versus 89.9% [319 of 355]; P = .1751). CONCLUSIONS: Doppler findings of absent or reversed umbilical artery end-diastolic flow are rare in recipient twins. Although immediate post-laser surgery survival is relatively decreased in this group, overall perinatal survival rates appear to be favorable.

Pre-Operative Twin Anemia/Polycythemia in the Setting of Twin-Twin Transfusion Syndrome (TTTS).

INTRODUCTION: Twin-twin transfusion syndrome (TTTS) and twin anemia-polycythemia sequence (TAPS) are classified as distinct clinical disorders associated with unbalanced blood flow through placental vascular communications. Typically, TAPS placentas demonstrate few <1 mm arteriovenous (AV) communications, and at fetoscopy the twins are visibly pale and plethoric. MATERIALS AND METHODS: In a cohort of TTTS patients who underwent laser surgery, those with preoperative findings suggestive of anemia/polycythemia (AP) were compared to those with TTTS alone. AP was defined as middle cerebral artery peak systolic velocity in one twin >1.5 multiples of the median (MoM), and <1.0 MoM in the other. RESULTS: Of 369 TTTS patients, 9 (2.4%) met criteria for preoperative AP. The mean number (±SD) of AV communications in the TTTS + AP group was 5.6 ± 5.7, compared with 8.8 ± 4.8 in the TTTS-alone group (p = 0.013). Five TTTS + AP patients (56%) had a few thin AV communications (mean 2.8 ± 1.6); all 5 had visibly pale and plethoric twins. The remaining 4 (44%) had large or numerous anastomoses (mean 10.5 ± 6.8); none had fetal skin color discordance. DISCUSSION: Preoperative AP affected 2% of TTTS patients. Of these, approximately half had placental and skin color findings typically reported with isolated TAPS.

De novo ACTG2 mutations cause congenital distended bladder, microcolon, and intestinal hypoperistalsis.

Megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS) is characterized by prenatal-onset distended urinary bladder with functional intestinal obstruction, requiring extensive surgical intervention for survival. While it is believed to be an autosomal recessive disorder, most cases are sporadic. Through whole-exome sequencing in a child with MMIHS, we identified a de novo mutation, p.R178L, in the gene encoding the smooth muscle gamma-2 actin, ACTG2. We subsequently detected another de novo ACTG2 mutation, p.R178C, in an additional child with MMIHS. Actg2 transcripts were primarily found in murine urinary bladder and intestinal tissues. Structural analysis and functional experiments suggested that both ACTG2 mutants interfere with proper polymerization of ACTG2 into thin filaments, leading to impaired contractility of the smooth muscle. In conclusion, our study suggests a pathogenic mechanism for MMIHS by identifying causative ACTG2 mutations.

Fetal surgery in complicated monoamniotic pregnancies: case series and systematic review of the literature.

OBJECTIVE: This study aimed to analyze perinatal outcome in monoamniotic (MA) pregnancies that underwent antenatal surgical interventions for fetal complications. METHODS: Review of all MA pregnancies treated with antenatal surgical interventions in three fetal treatment centers between 2000 and 2013. Indications were twin-twin transfusion syndrome, twin reversed arterial perfusion sequence, discordant anomalies, or elective reduction. We analyzed associations between indication, type of intervention, perinatal survival, and gestational age (GA) at birth and compared our results with a systematic review of the literature. RESULTS: Fifty-eight MA pregnancies were included. Median GA at treatment was 18.0 weeks (range: 13.1-33.0). Procedures included cord coagulation plus transection (n = 42), cord coagulation without transection (n = 7), laser coagulation of placental anastomoses (n = 7), and one case each with interstitial laser and radiofrequency ablation. Median GA at birth was 34 weeks (range 16.0-41.0), and 75% (53/71) of fetuses intended to survive indeed survived. Literature review included 20 articles, reporting on a total of 45 cases of surgically treated MA pregnancies, showing similar outcome results. CONCLUSION: We present the largest series concerning surgical interventions in complicated MA pregnancies. Despite being rare in experienced hands, a 75% survival is achieved. Collaboration between centers, data sharing, and benchmarking may further improve outcome.

Sequential laser surgery for twin-twin transfusion syndrome.

Treatment of twin-twin transfusion syndrome (TTTS) via the sequential selective laser photocoagulation of communicating vessels (SQLPCV) technique involves lasering the arteriovenous communications from the donor twin to the recipient twin first, followed by the arteriovenous communications from the recipient twin to the donor. Occluding the vascular communications in this particular order may result in transient intraoperative net transfusion to the donor twin and facilitate hemodynamic equilibrium, particularly to the volume depleted donor twin. Preliminary evidence suggests that the SQLPCV technique may result in improved perinatal outcomes compared with the standard selective (SLPCV) laser surgical approach. In this article, we describe the pathophysiological basis for this surgical approach, delineate the surgical technique, review the literature, and elaborate on the outstanding questions of the SQLPCV treatment of TTTS.

Vertical distribution and risk assessment of pharmaceuticals and other micropollutants in southern North Sea coastal waters.

Pharmaceutical compounds are micropollutants of emerging concern, as well as other classes of chemicals such as UV filters and artificial sweeteners. They enter marine environments via wastewater treatment plants, aquaculture runoff, hospital effluents, and shipping activities. While many studies have investigated the presence and distribution of these pollutants in numerous coastal areas, our study is the first to focus on their occurrence, spatial distribution, and vertical distribution in the sea surface microlayer (SML) and the near-surface layer of marine environments. We analyzed 62 pharmaceutical compounds, one UV filter, and six artificial sweeteners from the SML to the corresponding underlying water (0 cm, 20 cm, 50 cm, 100 cm, and 150 cm) at four stations in the southern North Sea. One station is the enclosed Jade Bay, one is the Weser estuary at Bremerhaven, and the other two stations (NS_7 and NS_8) are in the open German Bight. Jade Bay receives pollutants from surrounding wastewater treatment plants, while the Weser estuary receives pollutants from cities like Bremerhaven, which has dense populations and industrial activities. Concentrations of pharmaceutical compounds were higher in the upper water layers (from the SML to 20 cm). Eleven pharmaceutical compounds (caffeine, carbamazepine, gemfibrozil, ibuprofen, metoprolol, salicylic acid, clarithromycin, novobiocin, clindamycin, trimethoprim, and tylosin) were detected in >95 % of our samples. One UV filter (benzophenone-4) was found in 83 % and three artificial sweeteners (acesulfame, saccharin, and sucralose) in 100 % of all our samples. All artificial sweeteners posed high risks to the freshwater invertebrate Daphnia magna. Understanding the spatial and vertical distribution of pharmaceuticals and other micropollutants in marine environments may be essential in assessing their dispersal and detection in other aquatic environments.

Fetoscopic demonstration of feto-fetal hemorrhage before actual demise of a monochorionic twin, successful antenatal treatment, and narrative review of the literature.

Feto-fetal hemorrhage (FFH) through placental vascular anastomoses is believed to be responsible for the death or damage of a "second twin" after the demise of a "first twin (co-twin)" in monochorionic twin pregnancies. However, the timing of FFH has been difficult to determine. The resulting anemia in the surviving twin can be suspected by the finding of an elevated middle cerebral artery peak-systolic velocity (MCA-PSV), but this elevation may lag for at least 4 h after the demise of the first twin. Knowledge of the timing of FFH may have important clinical implications, as it may dictate if and when attempts to prevent death or damage to the second twin by delivery or intrauterine fetal transfusion would be warranted. We present a case that supports the notion that FFH occurs before the actual demise of the first twin. A review of the literature was also conducted.

Clinical assessment of the fetal right Quantitative Lung Index.

OBJECTIVES: We have previously described gestational-age-independent sonographic indices to assess fetal lung size in the right and left lungs: The Quantitative Lung Index for the right lung (QLI-R) and for the left lung (QLI-L), respectively. The purpose of this study was to evaluate the clinical cutoff point of the QLI-R to predict pulmonary hypoplasia and neonatal death. MATERIALS AND METHODS: Retrospective assessment of the QLI-R in patients with left-sided congenital diaphragmatic hernia (CDH-L) and other fetal conditions at risk for fetal pulmonary hypoplasia. Cross-section and longitudinal assessment of the behavior of the QLI-R in untreated and treated patients. ROC curve analysis to determine the optimal cutoff point of the QLI-R in predicting neonatal death. RESULTS: One hundred eighteen patients with CDH-L and other fetal conditions at risk for pulmonary hypoplasia had QLI-R measurements done. Seventeen patients were excluded for various reasons. Eleven patients with conditions other than CDH-L but at risk for pulmonary hypoplasia were used for intraclass coefficient measurements of the QLI-R. Ninety patients had CDH-L, of which 78 did not undergo antenatal intervention and in which the cutoff point for pulmonary hypoplasia and neonatal demise was assessed. Stent tracheal occlusion was performed in the remaining 12 patients with CDH-L, in which the behavior of the QLI after surgery was assessed. Analysis of the ICC showed an overall intra-rater reliability of 0.985 (Cronbach's Alpha-based). There was no correlation between gestational age and QLI-R (-0.73, Pearson correlation, p = .72). Twenty-six of the 78 patients (33%) with CDH-L managed expectantly had a neonatal demise. A QLI-R equal to or less than 0.45 was significantly predictive of neonatal demise (area under the curve 0.64, p = .046, sensitivity 77%). Nine of the 12 patients (75%) that underwent tracheal occlusion had neonatal survival. Of these, 10 had serial assessments of the QLI-R after surgery. An increase in the QLI-R of 0.11 was associated with a tendency for neonatal survival (p = .056). CONCLUSION: Our study confirms that the QLI-R is a gestational-age-independent measurement of fetal lung size, with a high degree of reproducibility. In a population of expectantly managed CDH-L patients, a cutoff value of the QLI-R of 0.45 or lower is predictive of neonatal death from pulmonary hypoplasia. The QLI-R can be used to monitor fetal lung growth after tracheal occlusion, and an increase in the QLI-R is suggestive of neonatal survival. Further prospective studies are needed to confirm these findings and to explore the use of the QLI in other populations at risk for pulmonary hypoplasia and consequent neonatal demise.