Feasibility of continuous intra-uterine pressure measurements during amnioreduction in twin-to-twin transfusion syndrome therapy.

INTRODUCTION: This work explores the feasibility of simultaneous and continuous intra-abdominal, intra-uterine, and arterial blood pressure measurements to examine the hemodynamic perturbation expected during therapeutic amnioreduction and to better understand the protective role of the placenta during that treatment. METHODS: Patients with twin-to-twin transfusion syndrome were treated with fetoscopic laser ablation followed by amnioreduction. Intra-abdominal, intra-uterine, and mean arterial pressures were simultaneously recorded during amnioreduction performed in steps of 200 mL. Placental thickness and uterine dimensions were measured before and after amnioreduction by ultrasonography. RESULTS: Useful pressure recordings were obtained between volume reduction steps and short hands-off periods in four studies. Median amnioreduction volume was 1400 mL corresponding to a median uterine volume reduction of 1121 mL. Mean intra-uterine pressure significantly fell from 24.8 to 13.6 mmHg (p = 0.011) and intra-abdominal pressure significantly decreased from 13.4 to 9.2 mmHg after amnioreduction (p = 0.015). Uterine pressure recordings revealed transient contractions (A, in mmHg) following individual amnioreduction steps, which increased with fractional amnioreduction (F, no dimension) (A = 17.23*F + 11.81; r = 0.50, p = 0.001). DISCUSSION: Simultaneous and continuous measurement of intra-abdominal, intra-uterine, and arterial blood pressures during amnioreduction is feasible. The dynamics reveal transient uterine contractions reaching levels comparable to those seen during childbirth which seem to oppose impending maternal hypovolemia by placental steal at the expense of temporarily reducing placental perfusion pressure and underline the importance of uterine and placental interaction.

Birth during off-hours: Impact of time of birth, staff´s seniority, and unit volume on maternal adverse outcomes-a population-based cross-sectional study of 87 065 deliveries.

BACKGROUND: The aim of this study was to investigate whether time of birth, unit volume, and staff seniority impact the incidence of maternal complications in deliveries ≥34 + 0 gestational weeks. METHODS: We conducted a population-based cross-sectional study of 87 065 deliveries occurring between 2004 and 2015 in ten public hospitals in Styria, Austria. A composite adverse maternal outcome measure of uterine atony, postpartum hysterectomy, postpartum bleeding, impaired wound healing, postpartum infections requiring antibiotic treatment, sepsis, or maternal death was used to compare outcomes by time of birth, unit volume, and staff seniority. Based on delivery data, generalized estimating equations (GEEs) were used to calculate the risk of maternal adverse outcomes. RESULTS: Maternal adverse events occurred in 1.33% of deliveries. Incidence of maternal adverse events was highest for units with >1000 deliveries (adjusted OR 1.40; CI 95%: 1.16-1.69) and higher for perinatal centers (adjusted OR 1.35; CI 95%: 1.15-1.57) compared with reference units (500-1000 deliveries/year). Delivery during the daytime compared with the afternoon and nighttime did not affect the incidence of maternal complications (P = 0.765 and P = 0.136, respectively). Compared with resident-guided deliveries, the odds ratio for an adverse event was the same when a consultant attended the delivery (adjusted OR 1.13; CI 95%: 0.98-1.30) but lower in deliveries managed by midwives only (adjusted OR 0.21; CI 95%: 0.07-0.64). CONCLUSION: Procedures performed during the night shift were not associated with increased complication rates. Delivery volume and high-volume centers were associated with the highest risk of maternal complications, and units with 500-1000 deliveries per year were the lowest. With increasing odds of pregnancy risks, these results change, and delivering in a high-volume center becomes at least as safe as delivering in a smaller unit.

Perinatal and 2-year neurodevelopmental outcome in late preterm fetal compromise: the TRUFFLE 2 randomised trial protocol.

INTRODUCTION: Following the detection of fetal growth restriction, there is no consensus about the criteria that should trigger delivery in the late preterm period. The consequences of inappropriate early or late delivery are potentially important yet practice varies widely around the world, with abnormal findings from fetal heart rate monitoring invariably leading to delivery. Indices derived from fetal cerebral Doppler examination may guide such decisions although there are few studies in this area. We propose a randomised, controlled trial to establish the optimum method of timing delivery between 32 weeks and 36 weeks 6 days of gestation. We hypothesise that delivery on evidence of cerebral blood flow redistribution reduces a composite of perinatal poor outcome, death and short-term hypoxia-related morbidity, with no worsening of neurodevelopmental outcome at 2 years. METHODS AND ANALYSIS: Women with non-anomalous singleton pregnancies 32+0 to 36+6 weeks of gestation in whom the estimated fetal weight or abdominal circumference is <10th percentile or has decreased by 50 percentiles since 18-32 weeks will be included for observational data collection. Participants will be randomised if cerebral blood flow redistribution is identified, based on umbilical to middle cerebral artery pulsatility index ratio values. Computerised cardiotocography (cCTG) must show normal fetal heart rate short term variation (≥4.5 msec) and absence of decelerations at randomisation. Randomisation will be 1:1 to immediate delivery or delayed delivery (based on cCTG abnormalities or other worsening fetal condition). The primary outcome is poor condition at birth and/or fetal or neonatal death and/or major neonatal morbidity, the secondary non-inferiority outcome is 2-year infant general health and neurodevelopmental outcome based on the Parent Report of Children's Abilities-Revised questionnaire. ETHICS AND DISSEMINATION: The Study Coordination Centre has obtained approval from London-Riverside Research Ethics Committee (REC) and Health Regulatory Authority (HRA). Publication will be in line with NIHR Open Access policy. TRIAL REGISTRATION NUMBER: Main sponsor: Imperial College London, Reference: 19QC5491. Funders: NIHR HTA, Reference: 127 976. Study coordination centre: Imperial College Healthcare NHS Trust, Du Cane Road, London, W12 0HS with Centre for Trials Research, College of Biomedical & Life Sciences, Cardiff University. IRAS Project ID: 266 400. REC reference: 20/LO/0031. ISRCTN registry: 76 016 200.

Amniodrainage-Induced Circulatory Dysfunction in Women Treated for Twin-To-Twin Transfusion Syndrome.

Twin-to-twin transfusion syndrome (TTTS) in monochorionic-diamniotic twin pregnancies usually requires fetoscopic laser ablation (FLA) followed by amniodrainage (AD). Perioperative maternal hemodynamic changes and hemodilution have been observed. Little is known about the underlying pathophysiology. We aimed to evaluate the impact of high volume amniodrainage on intrauterine pressure, placental thickness and maternal blood characteristics. A total of 18 cases of TTTS were included in this prospective pilot study. All patients were treated with FLA and subsequent AD. Intrauterine pressure and placental thickness were assessed before, during and after amniodrainage. Maternal hemoglobin, hematocrit and serum albumin were measured at admission and 24 h after the intervention. Amniodrainage led to a decrease in mean intrauterine pressure (from 30.1 ± 8.1 mmHg to 17.6 ± 3.6 mmHg (p < 0.001)) and an increase in mean placental thickness (from 16.8 ± 6.4 mm to 31.83 ± 8.64 mm (p < 0.001)). There was a positive correlation between changes in placental thickness and the amount of amniodrainage during intervention (Pearson's Rho 0.73; p = 0.001). Hematocrit decreased from 33.4 ± 3.8 (%) to 28.4 ± 3.5 (%), i.e., an increase in relative blood volume by 18 ± 10.2% (p < 0.001). Albumin decreased from 37.9 ± 0.9 g/L to 30.7 ± 2.2 g/L, i.e., an increase in relative plasma volume by 24 ± 8.1% (p < 0.001). Amniodrainage leads to uterine decompression, increased placental thickness and subsequent maternal hemodilution. We propose the term "amniodrainage-induced circulatory dysfunction" for these specific maternal hemodynamic changes in the treatment of twin-to-twin transfusion syndrome.

Post-Laser Twin Anemia Polycythemia Sequence: Diagnosis, Management, and Outcome in an International Cohort of 164 Cases.

The aim of this study was to investigate the management and outcome in the post-laser twin anemia polycythemia sequence (TAPS). Data of the international TAPS Registry, collected between 2014 and 2019, were used for this study. The primary outcomes were perinatal mortality and severe neonatal morbidity. Secondary outcomes included a risk factor analysis for perinatal mortality and severe neonatal morbidity. A total of 164 post-laser TAPS pregnancies were included, of which 92% (151/164) were diagnosed antenatally and 8% (13/164) postnatally. The median number of days between laser for TTTS and detection of TAPS was 14 (IQR: 7-28, range: 1-119). Antenatal management included expectant management in 43% (62/151), intrauterine transfusion with or without partial exchange transfusion in 29% (44/151), repeated laser surgery in 15% (24/151), selective feticide in 7% (11/151), delivery in 6% (9/151), and termination of pregnancy in 1% (1/151). The median gestational age (GA) at birth was 31.7 weeks (IQR: 28.6-33.7; range: 19.0-41.3). The perinatal mortality rate was 25% (83/327) for the total group, 37% (61/164) for donors, and 14% (22/163) for recipients (p < 0.001). Severe neonatal morbidity was detected in 40% (105/263) of the cohort and was similar for donors (43%; 51/118) and recipients (37%; 54/145), p = 0.568. Independent risk factors for spontaneous perinatal mortality were antenatal TAPS Stage 4 (OR = 3.4, 95%CI 1.4-26.0, p = 0.015), TAPS donor status (OR = 4.2, 95%CI 2.1-8.3, p < 0.001), and GA at birth (OR = 0.8, 95%CI 0.7-0.9, p = 0.001). Severe neonatal morbidity was significantly associated with GA at birth (OR = 1.5, 95%CI 1.3-1.7, p < 0.001). In conclusion, post-laser TAPS most often occurs within one month after laser for TTTS, but may develop up to 17 weeks after initial surgery. Management is mostly expectant, but varies greatly, highlighting the lack of consensus on the optimal treatment and heterogeneity of the condition. Perinatal outcome is poor, particularly due to the high rate of perinatal mortality in donor twins.

Effect of Intrauterine Growth Restriction on Cerebral Regional Oxygen Saturation in Preterm and Term Neonates during Immediate Postnatal Transition.

BACKGROUND: Intrauterine growth restriction (IUGR) is associated with adverse perinatal outcome. Affected fetuses commonly display typical blood flow redistribution towards the brain ("brain sparing"). Accordingly, increased cerebral oxygen saturation has been observed in IUGR neonates within the first days of life. AIM: The aim of our study was to assess cerebral oxygenation behavior during immediate neonatal transition in IUGR infants. METHODS: This is a retrospective single-center observational cohort study. Cerebral regional oxygen saturation (crSO2) was measured with near-infrared spectroscopy in neonates during the first 15 min after birth. Neonates with IUGR (IUGR group) were matched for gestational age (±1 week) and gender with neonates that were appropriate for gestational age (AGA). The AGA:IUGR matching ratio was 3:1. Arterial oxygen saturation (SpO2), heart rate (HR), crSO2, and cerebral fractional tissue oxygen extraction (cFTOE) were compared between the groups. RESULTS: Between August 2010 and October 2017, 45 neonates with IUGR were identified and matched to 135 AGA neonates. Mean gestational age was 33.1 ± 3.0 weeks in the IUGR group and 33.5 ± 2.7 weeks in the AGA group. Mean birth weight was 1,559 ± 582 g in the IUGR group and 2,051 ± 679 g in the AGA group. There was a significant group difference in crSO2 beginning at 5 min and continuing for the rest of the observation time with higher crSO2 values in the IUGR group (main effect group: p = 0.011; interaction time × group: p = 0.039). In cFTOE, a significant difference could be observed at 5-9 and 11-13 min with lower rates of oxygen extraction in the IUGR group (main effect group: p = 0.025; interaction time × group: p = 0.463). Concerning SpO2 and HR, there was no significant difference between the IUGR and the AGA neonates. CONCLUSION: Neonates of the IUGR group did show significantly higher crSO2 values and significantly lower cFTOE values already during immediate neonatal transition compared to the AGA group.

Maternal Complications and Hemodynamic Changes Following Intrauterine Interventions for Twin-to-Twin Transfusion Syndrome in Monochorionic Diamniotic Twin Pregnancies.

Twin-to-twin transfusion syndrome (TTTS) is a challenging complication in monochorionic diamniotic (MCDA) twins. Intrauterine interventions, such as fetoscopic laser ablation and cord occlusion followed by amniodrainage, are established treatments. Little is known about maternal complications and hemodynamics following these interventions. We performed a retrospective analysis of maternal procedure-related complications and the impact of such procedures on maternal hemodynamics and blood characteristics. Within the study period, 100 women with severe TTTS treated by fetoscopic laser ablation (FLA) or cord occlusion (CO) were identified. Clinically relevant maternal complications were reported in four (4%) cases. There was a significant decrease in hemoglobin, hematocrit, and albumin between admission and postoperative measurements (all p < 0.001). Systolic and diastolic blood pressure, as well as maternal heart rate, decreased from time of skin suture to postoperative measurements (all p < 0.001). Within a 24 h interval, there was a positive correlation between hematocrit (Spearman's rho 0.325; p = 0.003), hemoglobin (Spearman's rho 0.379; p < 0.001), and albumin (Spearman's rho 0.360; p = 0.027), and the amount of amniodrainage during the intervention. Maternal procedure-related complications are relatively rare. Significant hemodynamic alterations and maternal hemodilution are common clinical findings following intrauterine interventions.

A Modified Technique for Cord Transection in Monochorionic Monoamniotic Twin Pregnancies.

Monochorionic monoamniotic (MA) twins are at increased risk for intrauterine demise (IUD) and discordant anomalies. Selective feticide by cord occlusion may be an option in case of unfavorable discordant problems. In MA pregnancies, however, the surviving co-twin still remains at serious risk for IUD due to progressive cord entanglement. Cord transection has therefore been recommended to protect the survivor. This procedure may turn out to be difficult. We herein describe a modified fetoscopic technique for laser transection using a grasping forceps. We present technical details and clinical outcome in 2 cases of cord transection: one following cord occlusion and the other following spontaneous IUD. Cord transection was performed at 19 and 26 weeks gestation, respectively. A 3 Fr grasping forceps with a working length of 35 cm was used for controlled manipulation of the umbilical cord during transection. There were no procedure-related complications and both surviving co-twins had favorable neonatal outcome. Cord transection using a grasping forceps facilitates easy and precise fetoscopic release of the umbilical cord. To the best of our knowledge, this is the first report on post mortem cord transection after spontaneous single IUD with favorable outcome for the survivor.

Maternal Type 1 diabetes activates stress response in early placenta.

INTRODUCTION: Human pregnancy and in particular the first trimester, is a period highly susceptible towards adverse insults such as oxidative stress, which may lead to inadequate embryonic and feto-placental development. Diabetes mellitus is associated with increased oxidative stress caused by hyperglycemia, reactive oxygen species (ROS) production and inflammatory signals. In pregnancy, diabetes elevates the risk for early pregnancy loss, preeclampsia and fetal growth restriction, pathologies that origin from early placental maldevelopment. We hypothesized that maternal Type 1 diabetes mellitus (T1DM) induces oxidative stress in the first trimester human placenta. METHODS: We quantified stress induced, cytoprotective proteins, i.e. heat shock protein (HSP)70 and heme oxygenase (HO)-1 and determined protein modifications as markers for oxidation and glycation, i.e. levels of 4-hydroxynonenal (HNE) or Nε-(carboxymethyl)lysine (CML) modified proteins. Moreover, we measured expression levels of enzymes involved in antioxidant defense in the first trimester (week 7-9) placenta of normal and T1DM women by immunoblot and real-time qPCR. Primary human trophoblasts were isolated from first trimester placenta and the effects of oxygen, hyperglycemia and the pro-inflammatory cytokine tumor necrosis factor (TNF)-α on levels of HSP70 and HO-1 were analyzed. RESULTS: HSP70 (+19.9± 10.1%) and HO-1 (+63.5± 14.5%) were elevated (p < 0.05) in first trimester placenta of T1DM women when compared to normal women. However, levels of HNE or CML modified proteins were unchanged. Also, expression of most antioxidant enzymes was unchanged, with only superoxide dismutase 3 (SOD3) being upregulated by 3.0-fold (p < 0.05). In isolated primary trophoblasts, HSP70 and HO-1 were upregulated by increasing oxygen tension, but not by hyperglycemia or TNF-α. CONCLUSION: Although protein oxidation and glycation was not elevated, we infer that T1DM increases placental cellular stress in the first trimester. Elevated stress in early placenta of T1DM women may contribute to disturbances in placental development.