Perinatal outcomes of fetoscopic selective laser photocoagulation for spontaneous twin-anemia polycythemia sequence.

OBJECTIVES: Antenatal management of monochorionic pregnancies complicated by twin anemia polycythemia sequence (TAPS) remains sub-optimally defined. Our objective was to evaluate the safety and efficacy of fetoscopic selective laser photocoagulation with respect to fetal and neonatal survival. METHODS: A case series is reported with patients referred to the Texas Children's Fetal Center for evaluation and management of suspected spontaneous TAPS without concomitant twin-to-twin syndrome from 2014 to 2023. All evaluations were performed by our team and patients with stage II-IV TAPS were offered expectant management, intrauterine transfusion, or laser therapy. Cases of post-laser TAPS were excluded from this study. Pregnancy and neonatal outcomes were obtained from electronic medical records. RESULTS: During a 10-year time period, 18 patients presented to our center for the management of TAPS. Thirteen patients had stage II-IV TAPS (13/18, 72%) and elected to proceed with laser photocoagulation. All procedures were completed, and "solomonization" was performed for 12/13. Normalization of middle cerebral artery Dopplers in both fetuses was noted after all cases. There was one intrauterine fetal death of the 26 viable fetuses after laser treatment, which was complicated by selective growth restriction. Most patients (12/13) were delivered by Cesarean section at a mean gestational age of 29 ± 3 weeks. Subsequently, there was one ex-donor neonatal death in an infant who had prenatal hydrops. Overall, 30-day postnatal survival was 24/26 fetuses (92.3%). CONCLUSIONS: In the setting of spontaneous TAPS, laser therapy is feasible and appears to be an effective approach with overall favorable perinatal outcomes.

Outcomes of fetal lower urinary tract obstruction based on timing of oligohydramnios onset.

OBJECTIVE: Fetal Lower Urinary Tract Obstruction (LUTO) is associated with oligohydramnios and significant fetal morbidity, resulting in poor lung development and perinatal death. However, oligohydramnios may develop at different gestational periods, and the impact of timing on fetal outcomes remains unknown. Our objective was to characterize the impact onset of oligohydramnios had on prenatal outcomes. METHODS: This study is a retrospective cohort study of all patients with a prenatal diagnosis of LUTO at our tertiary referral center from 2014 to 2023. All patients underwent detailed ultrasonography and interdisciplinary counseling and were subsequently delivered at our institution. Data were obtained from electronic medical records and complete extraction was required for final inclusion. RESULTS: During the study time period, 93 patients met inclusion criteria of which 68 (73.1%) developed oligohydramnios during their pregnancy. 63 (93%) of these pregnancies resulted in livebirths with 28 (41.1%) perinatal deaths. Onset of oligohydramnios was earlier in pregnancies with perinatal death (23 vs. 28 weeks, p = 0.004) and associated with pulmonary hypoplasia. CONCLUSIONS: Our data show the impact of oligohydramnios timing in pregnancy on pulmonary hypoplasia and ultimately perinatal death. This allows for detailed patient counseling on the impact oligohydramnios may have on pregnancies by the gestational age of onset.

Impact of Transfer of Maternal Care for Fetal Anomalies on Maternal Depression and Anxiety Screening: A Prospective Cohort at a Tertiary Care Center.

INTRODUCTION: Perinatal depression and anxiety are major causes of maternal morbidity, and are more common in high-risk pregnancies compared to low-risk pregnancies. This study used validated screening tools to assess the prevalence of depression and anxiety symptoms in pregnant patients who transferred their obstetric care to a specialized fetal center for fetal anomaly. METHODS: This is a prospective cohort of patients with a fetal anomaly prompting transfer of obstetric care to Texas Children's Hospital Fetal Center between January 2021 and February 2022. The primary outcome was a self-assessed Edinburgh Postnatal Depression Scale score of 13 or higher, either antepartum or postpartum ("ever-positive EPDS"). Secondary outcomes included self-assessed Perinatal Anxiety Screening Scale (PASS) scores of 21 or higher ("ever-positive PASS"), obstetric outcomes, and neonatal outcomes. A frequentist analysis was performed. RESULTS: Of 149 women who transferred to Texas Children's Hospital during the study period, 94 enrolled in this study. Twenty-six percent of women had an ever-positive EPDS; 20% of patients had an ever-positive PASS. Patients were more likely to have an ever-positive EPDS if they were single (46% compared to 20%, p = 0.025). Women who had an ever-positive EPDS were more likely to be referred to psychiatry (46% compared to 14%, p = 0.004) and psychotherapy (29% compared to 1%, p < 0.001). Surprisingly, patients were more likely to have an ever-positive PASS if they reported good social support (p = 0.03). Antepartum EPDS and PASS scores had no relationship with postpartum EPDS scores. CONCLUSION: Women who transfer care to a tertiary setting have positive EPDS scores at double the rate of the general population, but tend to experience this either antepartum or postpartum (not both). Fetal centers should be prepared to screen for mental health symptoms before and after delivery and provide appropriate referral or treatment.

Laser therapy versus expectant management for selective fetal growth restriction in monochorionic twins: A systematic review.

Selective fetal growth restriction (sFGR) complicates 10%-26% of monochorionic twins. Treatment options include cord coagulation, expectant management, and fetoscopic laser photocoagulation. This review compared laser to expectant management for situations when cord coagulation is not an option. The MEDLINE, EMBASE, and Cochrane databases were queried for studies that compared laser to expectant management for sFGR. GRADE was used to assess quality prior to meta-analysis. A random-effects model was used to generate relative risks. Six studies were included, encompassing 299 pregnancies. One study was randomized and the remainder were retrospective cohorts. Laser is associated with more fetal deaths of the FGR twin compared to expectant management (risk ratio [RR] 2.5, 95% confidence interval [CI] 1.43-4.37, p = 0.001, I2 = 48%). Neonatal deaths and gestational age at delivery did not differ. Laser was associated with decreased abnormal neuroimaging in the AGA twin (RR 0.25, 95% CI 0.07-0.97, p = 0.05). Neurodevelopmental outcomes did not differ, although these data are limited. Laser causes more fetal deaths of the FGR twin without altering gestational age at delivery or rates of neonatal death. The literature is heterogeneous and the level of bias is high. Randomized trials that address laser for type II sFGR are needed and should include long-term neurological outcomes.

Solomon versus selective fetoscopic laser photocoagulation for twin-twin transfusion syndrome: A systematic review and meta-analysis.

This meta-analysis aims to compare the perinatal outcome of twin-twin transfusion syndrome (TTTS) pregnancies undergoing selective versus vascular equator (Solomon) fetoscopic laser photocoagulation (FLP). We performed a systematic search in PubMed and Web of Science from inception up to 25 July 2021. Studies comparing the Solomon and selective techniques of FLP for treatment of TTTS pregnancies were eligible. Random-effects or fixed-effect models were used to pool standardized mean differences (SMD) and log odds ratio. Seven studies with a total of 1664 TTTS pregnancies (n = 671 undergoing Solomon and n = 993 selective techniques) were included. As compared to the selective FLP, Solomon was associated with a lower risk of recurrent TTTS compared to the selective technique (Log odds ratio [OR]: -1.167; 95% credible interval [CrI]: -2.01, -0.33; p = 0.021; I2 : 67%). In addition, Solomon was significantly associated with a higher risk of placental abruption than the selective technique (Log [OR]: 1.44; 95% CrI: 0.45, 2.47; p = 0.012; I2 : 0.0%). Furthermore, a trend for the higher risk of preterm premature rupture of membranes was observed among those undergoing Solomon (Log [OR]: 0.581; 95% CrI: -0.43, 1.49; p = 0.131; I2 : 17%). As compared to selective FLP, the Solomon technique for TTTS pregnancies is associated with a significantly lower recurrence of TTTS; however, it significantly increases the risk of placental abruption.

Perinatal outcomes of twin-to-twin transfusion syndrome associated with evidence of twin anemia polycythemia using different standardized definitions.

OBJECTIVES: To evaluate the survival of twin-to-twin transfusion syndrome (TTTS) and concomitant twin anemia polycythemia sequence (TAPS) compared to TTTS without TAPS at the time of fetoscopic laser photocoagulation (FLP). METHODS: TTTS pregnancies undergoing FLP were divided to three groups including (i) traditional TAPS definition of middle cerebral artery (MCA) peak systolic velocity (PSV) < 1 multiple of the median (MoM) in recipient and > 1.5 MoM in the donor fetus, (ii) delta MCA-PSV > 0.5 MoM and (iii) delta MCA-PSV > 1.0 MoM. RESULTS: A total of 353 monochorionic twins underwent FLP for TTTS. Based on the traditional definition, 335 (94.9 %) had TTTS only and 18 (5.1 %) had TTTS + TAPS. There were 245 (69.4 %) TTTS only and 108 (30.6 %) TTTS + TAPS considering delta MCA-PSV > 0.5 MoM and 339 (96 %) TTTS only and 14 (4 %) TTTS + TAPS considering delta MCA-PSV > 1.0 MoM. No significant differences in survival were noted at birth or 30-days after delivery between TTTS and TTTS with TAPS patients using the traditional definition, delta > 0.5 MoM or delta > 1.0 MoM. CONCLUSION: The rate of neonatal survival at birth or at 30-days of life following FLP for TTTS only and TTTS with TAPS were not different based on any of the clinically used TAPS definitions.

Single fetal demise following fetoscopic ablation for twin-to-twin transfusion syndrome-cohort study, systematic review, and meta-analysis.

BACKGROUND: Several studies have assessed preoperative and operative factors associated with fetal demise after laser for TTTS, yet these findings are not completely conclusive. OBJECTIVE: This study aimed to identify risk factors for single fetal demise (recipient and donor twins) after fetoscopic laser photocoagulation for twin-to-twin transfusion syndrome. STUDY DESIGN: We searched PubMed, Scopus, and Web of Science systematically from the inception of the database to June 2020. We conducted a systemic review on studies investigating risk factors for fetal demise (donor and/or recipient) after fetoscopic laser photocoagulation in monochorionic pregnancies complicated with twin-to-twin transfusion syndrome. Initially, we investigated the cohort of women with twin-to-twin transfusion syndrome that underwent fetoscopic laser photocoagulation at our 2 high-volume fetal centers between 2012 and 2020 to identify risk factors for donor demise and recipient demise. Furthermore, we conducted a systematic review of the literature to better characterize these factors. Among studies that met the entry criteria, multiple preoperative and operative factors were tabulated. The random-effect model was used to pool the standardized mean differences or odds ratios and corresponding 95% confidence intervals. Heterogeneity was assessed using the I2 value. RESULTS: A total of 514 pregnancies with twin-to-twin transfusion syndrome managed with fetoscopic laser photocoagulation were included in the final analysis. Following the logistic regression, factors that remained significant for donor demise were selective fetal growth restriction (odds ratio, 1.9; 95% confidence interval, 1.3-2.8; P=.001) and umbilical artery blood flow with absent or reversed end-diastolic velocity of the donor (odds ratio, 2.06; 95% confidence interval, 1.2-3.4; P=.004). A significant factor associated with recipient demise was absent or reversed a-wave in the ductus venosus of the recipient (odds ratio, 1.74; 95% confidence interval, 1.07-3.13; P=.04). Data from 23 studies and our current cohort were included. A total of 4892 pregnancies with twin-to-twin transfusion syndrome managed with fetoscopic laser photocoagulation were analyzed for risk factors for donor demise, and 4594 pregnancies with twin-to-twin transfusion syndrome were analyzed for recipient demise. Among studies, the overall incidence rates ranged from 10.9% to 35.8% for donor demise and 7.3% to 24.5% for recipient demise. Significant risk factors for donor demise were intertwin estimated fetal weight discordance of >25% (odds ratio, 1.86; 95% confidence interval, 1.44-2.4; I2, 0.0%), selective fetal growth restriction (odds ratio, 1.78; 95% confidence interval, 1.4-2.27; I2, 0.0%), twin-to-twin transfusion syndrome stage III (odds ratio, 2.18; 95% confidence interval, 1.53-3.12; I2, 0.0%), umbilical artery blood flow with absent or reversed end-diastolic velocity of the donor (odds ratio, 2.31; 95% confidence interval, 1.9-2.8; I2, 23.7%), absent or reversed a-wave in the ductus venosus of the donor (odds ratio, 1.83; 95% confidence interval, 1.45-2.3; I2, 0.0%), and presence of arterioarterial anastomoses (odds ratio, 2.81; 95% confidence interval, 1.35-5.85; I2, 90.7%). Sequential selective coagulation was protective against donor demise (odds ratio, 0.31; 95% confidence interval, 0.16-0.58; I2, 0.0%). Significant risk factors for recipient demise were twin-to-twin transfusion syndrome stage IV (odds ratio, 2.18; 95% confidence interval, 1.01-4.6; I2, 16.5%), umbilical artery blood flow with absent or reversed end-diastolic velocity of the recipient (odds ratio, 2.68; 95% confidence interval, 1.91-3.74; I2, 0.0%), absent or reversed a-wave in the ductus venosus of the recipient (odds ratio, 2.37; 95% confidence interval, 1.55-3.64; I2, 60.2%), and middle cerebral artery peak systolic velocity of >1.5 multiple of the median (odds ratio, 3.06; 95% confidence interval, 1.36-6.88; I2, 0.0%). CONCLUSION: Abnormal blood flow patterns represented by abnormal Doppler studies and low fetal weight were associated with single fetal demise in women with twin-to-twin transfusion syndrome undergoing laser therapy. Although sequential selective coagulation was protective against donor demise, the presence of arterioarterial anastomoses was considerably associated with donor demise. This meta-analysis extensively investigated the association of a wide range of preoperative and operative factors with fetal demise. These findings may be important inpatient counseling, in further understanding the disease, and perhaps in improving surgical techniques.

Fetal reduction of triplet pregnancies to twins vs singletons: a meta-analysis of survival and pregnancy outcome.

OBJECTIVE: This systematic review and meta-analysis aimed to compare the fetal survival rate and perinatal outcomes of triplet pregnancies after selective reduction to twin pregnancies vs singleton pregnancies. DATA SOURCES: PubMed, Web of Science, Scopus, and Embase were systematically searched from the inception of the databases to January 16, 2022. STUDY ELIGIBILITY CRITERIA: Studies comparing the survival and perinatal outcomes between reduction to twin pregnancies and reduction to singleton pregnancies were included. The primary outcomes were fetal survival, defined as a live birth at >24 weeks of gestation. The secondary outcomes were gestational age at birth, preterm birth at <32 and <34 weeks of gestation, early pregnancy loss (<24 weeks of gestation), low birthweight, and rate of neonatal demise (up to 28 days after birth). METHODS: The random-effect model was used to pool the mean differences or odds ratios and the corresponding 95% confidence intervals. To provide a range of expected effects if a new study was conducted, 95% prediction intervals were calculated for outcomes presented in >3 studies. RESULTS: Of note, 10 studies with 2543 triplet pregnancies undergoing fetal reduction, of which 2035 reduced to twin pregnancies and 508 reduced to singleton pregnancies, met the inclusion criteria. Reduction to twin pregnancies had a lower rate of fetal survival (odds ratio, 0.61; 95% confidence interval, 0.40-0.92; P=.02; 95% prediction interval, 0.36-1.03) and comparable rates of early pregnancy loss (odds ratio, 0.89; 95% confidence interval, 0.58-1.38; P=.61; 95% prediction interval, 0.54-1.48) and neonatal demise (odds ratio, 0.57; 95% confidence interval, 0.09-3.50; P=.55) than reduction to singleton pregnancies. Reduction to twin pregnancies had a significantly lower gestation age at birth (weeks) (mean difference, -2.20; 95% confidence interval, -2.80 to -1.61; P<.001; 95% prediction interval, -4.27 to -0.14) than reduction to singleton pregnancies. Furthermore, reduction to twin pregnancies was associated with lower birthweight and greater risk of preterm birth at <32 and <34 weeks of gestation. CONCLUSION: Triplet pregnancies reduced to twin pregnancies had a lower fetal survival rate of all remaining fetuses, lower gestational age at birth, higher risk of preterm birth, and lower birthweight than triplet pregnancies reduced to singleton pregnancies; reduction to twin pregnancies vs reduction to singleton pregnancies showed no substantial difference for the rates of early pregnancy loss and neonatal death.

Perinatal characteristics and early childhood follow up after ex-utero intrapartum treatment for head and neck teratomas by prenatal diagnosis.

BACKGROUND: Ex utero intrapartum treatment (EXIT) is utilized for safe delivery when a baby has a compromised airway. The purpose of this retrospective study was to examine the indications and outcomes of 11 children presenting with airway occluding oropharyngeal and cervical teratomas. METHODS: Study of all children with an airway occluding teratoma delivered via EXIT (2001-2018) in our unit. Primary outcomes included survival and tracheostomy at discharge. Data are reported using descriptive statistics as median (range) and rate (%). RESULTS: We performed 45 EXIT procedure performed between January 2001 and April 2018. Of these, eleven were for cervical and/or upper airway teratoma. Ten (91%) cases had associated polyhydramnios, two (18%) developed nonimmune hydrops, and eight (72%) delivered preterm. Six (45.5%) were performed as an emergency. Estimated blood loss was 1000 ml (500, 1000). The neonatal mortality rate was 18% (2/11) and 33% (3/9) of the survivors were discharged with a tracheostomy. CONCLUSION: EXIT is a reasonable option for delivery of babies with an occlusive upper airway mass. Neonatal survival depends on individualized factors but may be as high as 82% in those with teratoma.

Umbilical Artery Doppler Patterns and Right Ventricular Outflow Abnormalities in Twin-Twin Transfusion Syndrome.

OBJECTIVES: To evaluate the association of abnormal Doppler velocimetric patterns in the umbilical arteries (UAs) and right ventricular outflow tract abnormalities (RVOTAs) in twin- twin transfusion syndrome (TTTS) cases. METHODS: This retrospective study involved women who had laser surgery for TTTS between January 2012 and May 2018 at a single institution. The prevalence of an RVOTA in either twin was compared among TTTS cases in which both twins had positive end-diastolic flow (EDF) in the UA and those in which either twin had intermittent or persistent absent/reversed UA EDF. Nonparametric tests were used for comparisons. Logistic regression was performed to identify variables associated with an RVOTA in either twin, adjusted for moderate or severe tricuspid regurgitation, right ventricular hypertrophy, right ventricular systolic or diastolic dysfunction, the Quintero stage, and other confounders. P < .05 was considered significant. RESULTS: A total of 126 consecutive TTTS cases were included. Right ventricular outflow tract abnormalities were seen in 8.7% (11of 126) of cases, all in recipient twins. Significant differences in the rate of RVOTAs in the recipient twin were seen between TTTS cases with intermittent absent/reversed UA EDF and those with positive UA EDF (26.9% [7 of 26] versus 3.7% [3 of 82]; P = .002]. However, no significant differences were noted among the other study groups. Intermittent absent/reversed UA EDF was associated with a significantly increased risk for an RVOTA (adjusted odds ratio, 20.6 [95% confidence interval, 3.1-138]; P = .002) after adjusting for confounders. CONCLUSIONS: Intermittent changes in vascular impedance to UA flow may contribute to the pathogenesis of acquired right-sided cardiac lesions in the recipient twin affected with TTTS.

Intrauterine Transfusion Complicated by Umbilical Artery Thrombosis.

BACKGROUND: Fetal anemia results from several conditions; however intrauterine transfusion (IUT) remains the treatment for severe cases. The complications of this procedure are rare and yet can result in preterm delivery or fetal death. CASE: 31 y/o G3P2002 with Rh alloimmunization underwent IUT from 19 to 35 weeks. Umbilical artery thrombosis was noted after her 5th IUT. Further transfusions were performed without any complications and she delivered a full term male infant with APGARS of 8 and 9 at 1 and 5 minutes, respectively. CONCLUSION: The complication of umbilical artery thrombosis is unusual and the optimal management is unclear. We report such a case and propose that the presence of Hyrtl's anastomosis near the placental cord insertion may explain the reassuring fetal status throughout the pregnancy.

Exploring the Pharmacokinetic Profile of Remifentanil in Mid-Trimester Gestations Undergoing Fetal Intervention Procedures.

Background: Indications for surgery during pregnancy have increased. Specifically fetal interventions have increased from conditions that were considered lethal like twin-twin transfusion syndrome and severe fetal anemia to non-lethal conditions like myelomeningocele. The optimal anesthetic agent for in utero surgery is yet to be determined. Success of the procedure is often dictated by the efficacy of the anesthetic to immobilize the fetus without over-sedating mom. Remifentanil is used as preferred agent due to its short half-life however pharmacokinetics in pregnancy is unknown. Objective: To determine the pharmacokinetic parameters of remifentanil in a mid-trimester pregnant patient population undergoing fetal intervention. Study Design: A validated liquid chromatography assay with ultraviolet absorbance was employed to estimate maternal serum remifentanil levels. Blood samples were obtained at baseline and at selected time points: 5, 15, 30, 45, 60 min after the beginning of the remifentanil infusion and at 15, 30, and 60 min post end of infusion. Results: Ten pregnant patients were enrolled in the study however only eight patients had sampling obtained at all time points. The mean gestational age was 22.2 (±2.7) weeks, maternal age was 27.8 (±5.1) years and body mass index was 29.6 (±6.3). After receiving a continuous infusion of remifentanil, mean total dose was 975.3 µg, Cmin was 2.0 ng/mL and Cmax was 8.4 ng/mL. A two-compartment model best described the plasma remifentanil data. Mean pharmacokinetic parameters were: volume of distribution (Vdc) = 124.6 L (16.2-530.8 L), maternal remifentanil total clearance (Clt) = 170.7 L/h (17.7-486.9 L/h), and half-life (t½) = 0.6 h (0.2-0.9 h). The maternal remifentanil area under the curve (AUC) ranged from 2.7 to 21.7 µg/L*h. The mean alpha-acidic glycoprotein was 124.8 mg/dL (81.3-149.8). Conclusion: The pharmacokinetic profile of remifentanil in pregnant women is similar to previously reported general population profiles. This data did provide potential rationale for the clinical observations why when remifentanil is dosed based on non-pregnant guidelines, it did not uniformly provide adequate fetal immobilization as per anecdotal perception of operating fetal surgeons. These findings are important for the development of further clinical studies to optimize dosing for surgery during pregnancy including the estimation of placental transfer and total fetal exposure.