Roopali Donepudi

Does anemia-polycythemia complicating twin-twin transfusion syndrome affect outcome after fetoscopic laser surgery?

Twin anemia–polycythemia sequence (TAPS) can occur as a unique disease or as a complication of twin–twin transfusion syndrome (TTTS). Middle cerebral artery (MCA) Doppler studies are not currently part of the routine evaluation of monochorionic twins since they are not used in the Quintero staging system. As such, the true incidence of TAPS is unknown. We aimed to compare the characteristics and outcomes of twin pregnancies with TTTS complicated by spontaneous anemia–polycythemia vs those with TTTS alone.

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.

Recipient umbilical artery elongation (redundancy) in twin-twin transfusion syndrome

BACKGROUND: Chronic hypertension in adults causes arterial lengthening in major arteries, but the effects of early fetal hypertension on the twin‐twin transfusion syndrome recipients vascular architecture remains unknown. OBJECTIVE: We hypothesize that arterial cord redundancy is related to recipient hypertension and subsequent heart failure. Our objectives were to: (1) establish a 3‐dimensional color Doppler ultrasound method of measuring umbilical arterial length relative to its corresponding venous segment in the umbilical cord using artery vein angle; (2) compare recipient artery vein angle to gestational age‐matched controls; and (3) test the association of artery vein angle with recipient heart failure. STUDY DESIGN: We compared 3 groups prospectively: twin‐twin transfusion syndrome pregnancies undergoing fetoscopic laser surgery (preoperatively) and 2 groups of gestational age‐matched controls: uncomplicated monochorionic‐diamniotic twin pregnancies and healthy singletons. Using a 3‐dimensional color‐Doppler volume image of 5 cm of cord near the placental insertion, we traced the umbilical artery and vein producing umbilical artery:vein length, (artery vein index) and measured the artery vein angle between umbilical artery and vein. Correlation of artery vein angle to twin‐twin transfusion syndrome stage, maximum vertical pocket, umbilical arterial indices, ductus venosus Doppler, and brain natriuretic peptide were performed. We used pulsed‐wave and tissue Doppler to measure tissue Doppler velocities and indexed cardiac output and correlated these with artery vein angle. Comparative statistics, including multivariable linear regression, examined the relationship between umbilical arterial Doppler indices and artery vein angle. RESULTS: Artery vein angle and artery vein index correlated significantly (R2, 0.86; P < .0001), hence, artery vein angle was used for analysis. Mean artery vein angle was 33.1 ± 31.5 degrees in recipients (n = 44), 9.5 ± 6 degrees in monochorionic‐diamniotic (n = 11; 22 fetuses), and 8.9 ± 8.3 degrees in singleton controls (n = 16) (P < .001). An artery vein angle ≥26 degrees (>95th percentile for controls) was measured in 52% recipients. Artery vein angle was higher in twin‐twin transfusion syndrome stage 3R vs 1 (P = .001). Artery vein angle increased with increasing umbilical arterial pulsatility index (P < .001), and decreased with increasing resistance index (P = .02) after adjusting for gestational age. Interrater agreements to categorize abnormal artery vein angle values was 95% (P < .001). Abnormal ductus venosus Doppler and elevated recipient amniotic fluid N‐terminal pro‐brain natriuretic peptide/protein levels correlated significantly with artery vein angle. Abnormal artery vein angles were associated with decreased indexed cardiac output, lower tissue Doppler velocities, higher right‐sided Tei indices, and severe tricuspid regurgitation. CONCLUSION: Umbilical arterial lengthening occurs in 52% of recipients and is associated with abnormal Doppler flows, low systolic tissue Doppler velocities, reduced cardiac output, and elevated markers of cardiac failure. This may reflect chronicity and severity of hypertension in the recipient fetus. Further research is needed to explore the mechanisms of elongation and long‐term implications.

OC18.07: Reduced ventricular strain initiates cardiovascular compromise in monochorionic pregnancies

Objectives: Review outcome following interventional and expectant management of MCDA twin pregnancies complicated with selective intrauterine growth restriction (sIUGR) and absent or reverse end-diastolic flow (AREDF) in the umbilical arteries. Methods: All cases of sIUGR defined as abdominal circumference (AC) <5th centile and AREDF before 26+6 weeks, between 2011 and 2017. Management options included selective fetoscopic laser coagulation (SFLC) of inter-twin anatomoses, cord coagulation (CC), or expectant management (EM). Discordance in EFW and positive a-wave on the ductus venosus (DV) at diagnosis were considered as potential predictors for perinatal survival. Results: Of 108 cases, 13, 50 and 45 were managed by SFLC, CC and EM. Overall survival was 23%(6/26), 40%(40/100) and 77.8%(70/90) respectively. The discordance in EFW at diagnosis was more marked and negative a-wave in DV was more prevalent in both intervention groups. Intrauterine demise of the co-twin occurred in 30.8%(4/13), 10%(5/50) and 6.7%(3/45) respectively and was associated with demise of the smaller twin following SFLC and EM in 76.9%(10/13) and 17.8%(8/45) respectively. AC < 3 z-scores and absent a-wave in the ductus venosus were predictive of spontaneous demise in the EM group. Mean gestational age at delivery was 30 (29-32), 35 (32-35) and 32 (29-32) weeks following SFLC, CC and EM respectively. Conclusions: SFLC yielded poor results. Expectant management is a valid option as some will improve and allow a favourable neonatal outcome with few spontaneous fetal demise during follow-up. However, in cases with high discordance, AREDF and abnormal DV Doppler, CC should be considered to protect the co-twin.

Perinatal outcomes of single fetal survivor after fetal intervention for complicated monochorionic twins

To compare perinatal outcomes between acute single fetal demise following fetoscopic laser photocoagulation to planned selective reduction (SR) in complicated monochorionic twin pregnancies.

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

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

Recurrent Twin‐Twin Transfusion Syndrome (rTTTS) and Twin Anemia Polycythemia Sequence (TAPS) after fetoscopic laser surgery (FLS): size (of the cannula) does matter

The optimal outcome after fetoscopic laser surgery (FLS) for twin–twin transfusion syndrome (TTTS) depends on the successful ablation of all placental anastomoses. The objective of this study was to determine the incidence of and risk factors for recurrent TTTS (rTTTS) or twin anemia–polycythemia sequence (TAPS) after FLS, focusing on the impact of cannula diameter.

Response to: Milosavljevic et al. “Two cases of RIT1 associated Noonan syndrome: Further delineation of the clinical phenotype and review of the literature”

1Department of Obstetrics, Gynecology, and Reproductive Sciences, McGovern Medical School at UT Health and The Fetal Center at Children’s Memorial Hermann Hospital, Houston, Texas 2Maternal Fetal Medicine Associates of South Texas, Webster, Texas Correspondence Blair Stevens, Department of Obstetrics, Gynecology, and Reproductive Sciences, McGovern Medical School at UT Health and The Fetal Center at Children’s Memorial Hermann Hospital, 6410 Fannin St. Suite 1217, Houston, TX 77030. Email: blair.k.stevens@uth.tmc.edu