Michael Tchirikov

Long-term amnioinfusion through a subcutaneously implanted amniotic fluid replacement port system for treatment of PPROM in humans

OBJECTIVES To introduce a novel method for the treatment of PPROM (preterm premature rupture of membranes) using continuous amnioinfusion via a subcutaneously implanted port system. STUDY DESIGN After development and testing since 2001 in a fetal sheep model, the port system has been successfully implanted in two humans with PPROM. In the first case, the subcutaneous port system was implanted during the 23rd week of gestation in a 39-year-old 5th-gravida with PPROM since the 18th week of gestation; in the second case, the port system was implanted during the 24th week of gestation in a 27-year-old 3rd gravida with PPROM since the 21st week of gestation. After port implantation, 100ml/h saline solution was infused intermittently into the amniotic cavity. The whole course of treatment was supported by tocolysis. RESULTS In the cases presented, gestation was terminated by cesarean section, in one case in the 29th week of gestation, and in the other case in the 30th week. The newborns showed no signs of lung hypoplasia and were successfully extubated on the 1st or 2nd day after delivery. Six months later the children did not exhibit any deviation from the normal development. CONCLUSION Long-term amnioinfusion via a subcutaneously implanted port system could be used in humans with PPROM for prolongation of pregnancy and to avoid lung hypoplasia. Prospective randomized studies are ongoing.

Cardiac output and blood flow volume redistribution during acute maternal hypoxia in fetal sheep

Abstract Objective: Acute hypoxia is one of the main causes of poor neonatal outcome. The aim of this study was the investigation of cardiac output (CO) and blood flow redistribution following induction of acute hypoxia in a fetal sheep model. Method: We investigated 10 fetal sheep between 108 and 130 days of gestation. Acute hypoxia was induced by reducing the O2 saturation in the ventilated gas mixture of the maternal sheep to ∼75%. The CO, placental fraction of CO, Doppler parameters in the ductus venosus (DV), umbilical artery (UA) and vein (UV) were measured. Results: The fetal pO2 decreased from 47.1 (7.19; 7.35) to 6.89 (6.78; 7.11) mm Hg [P=0.01, median, (95% CI)] during hypoxia. Fetal pH and BE were also significantly reduced. The DV/UV fraction increased from 15.3 (11.5; 19.8) to 51.1 (35.9; 62.1) (P=0.0001). The combined cardiac output [1228.1 (1024.3; 1686.4) vs. 987.8 (834, 1261) mL min–1], the placental fraction of the CO [31.5 (26; 42.1) vs. 26.9 (20.6; 29.3)%] and the right to left (R/L) heart ratio [1.76 (1.5; 2.2) vs. 1.3 (1.1; 1.6)] significantly decreased during hypoxia. Conclusions: Acute hypoxia significantly increases the proportion of the placental blood passing through the DV and reduces the placental fraction of CO and the R/L heart ratio. These findings could be used as early signs of acute fetal hypoxia.

Dilation of the ductus venosus by stent implantation increases placental blood perfusion in fetal sheep

OBJECTIVE The reduction of resistance to flow in the ductus venous (DV) and a decrease of blood supply to the liver serve for the survival of the fetus during hypoxia. The present study investigated the influence of the increased diameter of the DV on placental blood perfusion. STUDY DESIGN In 15 ewes with twin pregnancies at gestational ages of 117 +/- 4 days, a stent (4 or 5 mm) was placed into the DV of 1 twin (DV(stent) group) under ultrasound guidance. Blood flow rates in the umbilical vein (UV) and DV of both fetuses were measured using Doppler ultrasound. Eight pairs of twin fetuses were included for the final analysis. RESULTS The dilatation of the DV increased the blood flow volume rate passed through the DV from 136.61 +/- 41.07 to 398.93 +/- 86.62 (mL/min(-1), P < .0001) and also significantly increased placental blood perfusion from 454.35 +/- 143.0 in control twin to 663.56 +/- 167.36 in the DV(stent) group (P < .05, mL/min(-1)), respectively. The DV/UV ratio increased from 30.6 +/- 11.6% in the control group to 58.9 +/- 11.6% in DV(stent) gemini (P < .0001). The positive effect of DV dilation on the placental blood perfusion was stable and could be observed up to 3 weeks after the operation. CONCLUSION The dilatation of the DV by means of stent implantation in the DV increased the blood flow volume rate in the umbilical vein. Fetal surviving mechanism, the increase of DV shunting rate including redistribution of the blood flow in the liver with a reduction of DV resistance to flow, could have a second effect: the improvement of reduced placental blood perfusion during hypoxia.

Neonatal outcome using ultrathin fetoscope for laser coagulation in twin-to-twin-transfusion syndrome

Abstract Objective: To improve neonatal outcome using ultrathin fetoscope for laser treatment of twin-to-twin transfusion syndrome. Methods: Retrospective cohort study of a series of 80 cases of twin-to-twin-transfusion syndrome prior to 26 weeks’ gestation subjected to laser coagulation by means of a 1.0/1.2 mm fiber fetoscope with a sheath sectional area 2.65 mm2/3.34 mm2 (n=27) and a 2.0 mm classic lens fetoscope with a sheath sectional area: 6.63 mm2/11.27 mm2 (n=53). Results: The survival rates of at least one twin in the compared groups were 94.4% (classic optic) and 100% (ultrathin optic), for both twins: 75.5% and 83.3%, respectively. By decreasing sheath diameter a pregnancy was prolonged by an average of 21.3 days (P=0.0045), with a resulting increase in the recipient’s weight of 389 g (P=0.0049) and an increase in the donor’s Apgar score. However, the intervention with ultrathin optic took 11 min longer (P=0.031). Conclusion: The reduction of the iatrogenic damage of the amniotic membrane using ultrathin fetoscope with a small sheath, significantly improves the neonatal outcome after laser treatment of twin-to-twin-transfusion syndrome. The operator should only commence working with the 1 mm fetoscope after the learning curve has been accomplished.

Cardiac output following fetoscopic coagulation of major placental vessels in fetal sheep.

To measure changes in cardiac output (CO) after partial cord occlusion in fetal sheep in order to investigate pathophysiological fetal adaptation mechanisms in a simulated acute placental insufficiency model under standardized conditions, with the aim of finding relevant methods for monitoring human fetuses during stress situations.

The effect of intraumbilical fetal nutrition via a subcutaneously implanted port system on amino acid concentration by severe IUGR human fetuses.

Abstract Objective: To determine if intrauterine intraumbilical supplementation with amino acids (AA) and glucose can improve neonatal outcome of severe growth restricted human fetuses (IUGR). Methods: Prospective pilot study of intrauterine treatment of severe IUGR fetuses [n=14, 27 weeks of gestation (range 23–31)] with cerebroplacental ratio <1, with long-term intraumbilical AA and glucose supplementation (10% of feto-placental blood volume/day) using a perinatal port system alone (n=5) or combined with hyperbaric oxygenation (n=1, HBO) vs. control group (n=8). Results: The duration of continuous intraumbilical AA/glucose supplementation was 11 (6–13) days. Daily intravascular fetal nutrition significantly prolonged the brain sparing to delivery interval by 24 (14–33) days vs. 5.6 (2–12) days in controls. Fetal nutrition reduced blood flow resistance in the placental circulation but did not affect the Doppler profile of cerebral arteries. Higher weight gain of 113.5 (36–539) g was observed following supplementation compared to 33.3 (8–98) g in the control group (P<0.05). In spite of this, fetuses below 28 weeks of gestation did not sufficiently benefit from infused commercial AA. We found a reduced fetal plasma concentration of the essential AA histidine, threonine, lysine and arginine, and non-essential AA taurine, in severe IUGR fetuses in both groups. Long-term supplementation with a commercial AA formula led to a slight, but not significant, reduction of histidine, threonine, lysine, arginine, asparagine and glutamine. However, the concentration of tryptophan and glutamic acid slightly increased. HBO can be combined with AA supplementation via a port system. In one case, the port system was also successfully used for fetal blood transfusion. Conclusions: Intravascular treatment of IUGR with fetal nutrition can prolong pregnancy with severe placental insufficiency and brain sparing for many weeks. However, rather than normalizing AA concentrations, an enhanced AA imbalance was observed in IUGR fetuses following supplementation. These deviations in AA concentrations prevent the recommendation for use of commercial AA solutions for prenatal treatment of extreme preterm IUGR fetuses.

Three years' experience of using a 29-gauge atraumatic needle for amniocentesis.

Abstract Aims: To quantify the procedure-related complication rate after using modified technique of amniocentesis with a 29-gauge (29-G) pencil-point needle. Methods: This is a prospective, descriptive study of 316 amniocenteses that were performed by means of atraumatic 29-G pencil-point needle under ultrasound control. Results: A total of 316 amniocenteses were observed through the postprocedural period. The median time needed to retrieve 15 mL of amniotic fluid was 4 min. A total of 19 pregnancies were terminated after genetic testing. No case was regarded as procedure-related fetal loss. No other complications were observed. Seventeen children were born before 37 completed weeks of gestation and five children had a birth weight <2000 g. Conclusions: Amniocentesis with the 29-G atraumatic pencil-point needle seems to be a safe procedure with extremely low risk of complications and is a good alternative to the traditional 22-G Quincke needle.

A 29-gauge atraumatic needle for amniocentesis.

Abstract Objective: To compare perforation characteristics of standard 22 G (0.7 mm) to 29 G needle (0.34 mm) for amniocentesis. Methods: Seventeen human chorio-amnion membranes were perforated immediately after cesarean section using 22 G needle for spinal anesthesia and 29 G “pencil-point” needles for amniocentesis under in-vitro conditions. Area of perforation was determined using a microscope and volume of fluid leakage was measured over a period of 5 min. Results: Membrane perforation with the 22 G needle resulted in a mean damaged area of 225,147.4 μm2, a hole with a mean area of 50,154 μm2 and amniotic fluid volume passage of 17.5 mL/5 min, whereas the 29 G needle generated a mean damaged area of 114,812.4 μm2, a hole with an average area of 1382.5 μm2 and volume passage of 0.28 mL/5 min. These differences were significant. Conclusion: The hole formed by membrane perforation with 29 G “pencil-point” needle for amniocentesis is 36 times smaller, and the amniotic fluid loss is 61 times less than that measured with the 22 G standard needle for spinal anesthesia. Significant reduction of complications following amniocentesis is expected with the 29 G needle.

Two New Approaches in Intrauterine Tracheal Occlusion Using an Ultrathin Fetoscope

To introduce and establish a new approach in minimal invasive fetoscopic surgery in order to reduce access trauma and the iatrogenic preterm premature rupture of the membranes (PPROM) as a major complication of intrauterine treatment of congenital diaphragmatic hernia.

Reference Curve for the Mean Uterine Artery Pulsatility Index in Singleton Pregnancies

INTRODUCTION Doppler sonography of the uterine artery (UA) is done to monitor pregnancies, because the detected flow patterns are useful to draw inferences about possible disorders of trophoblast invasion. Increased resistance in the UA is associated with an increased risk of preeclampsia and/or intrauterine growth restriction (IUGR) and perinatal mortality. In the absence of standardized figures, the normal ranges of the various available reference curves sometimes differ quite substantially from one another. The causes for this are differences in the flow patterns of the UA depending on the position of the pulsed Doppler gates as well as branching of the UA. Because of the discrepancies between the different reference curves and the practical problems this poses for guideline recommendations, we thought it would be useful to create our own reference curves for Doppler measurements of the UA obtained from a singleton cohort under standardized conditions. MATERIAL AND METHODS This retrospective cohort study was carried out in the Department of Obstetrics of the Charité - Universitätsmedizin Berlin, the Department for Obstetrics and Prenatal Medicine of the University Hospital Halle (Saale) and the Center for Prenatal Diagnostics and Human Genetics Kurfürstendamm 199. Available datasets from the three study locations were identified and reference curves were generated using the LMS method. Measured values were correlated with age of gestation, and a cubic model and Box-Cox power transformation (L), the median (M) and the coefficient of variation (S) were used to smooth the curves. RESULTS 103 720 Doppler examinations of the UA carried out in singleton pregnancies from the 11th week of gestation (10 + 1 GW) were analyzed. The mean pulsatility index (Mean PI) showed a continuous decline over the course of pregnancy, dropping to a plateau of around 0.84 between the 23rd and 27th GW, after which it decreased again. CONCLUSION Age of gestation, placental position, position of pulsed Doppler gates and branching of the UA can all change the flow pattern. The mean pulsatility index (Mean PI) showed a continuous decrease over time. There were significant differences between our data and alternative reference curves. A system of classifying Doppler studies and a reference curve adapted to the current technology are urgently required to differentiate better between physiological and pathological findings.