Predicting the likelihood of successful medical treatment of early pregnancy loss: development and internal validation of a clinical prediction model.

STUDY QUESTION: What are clinical predictors for successful medical treatment in case of early pregnancy loss (EPL)? SUMMARY ANSWER: Use of mifepristone, BMI, number of previous uterine aspirations and the presence of minor clinical symptoms (slight vaginal bleeding or some abdominal cramps) at treatment start are predictors for successful medical treatment in case of EPL. WHAT IS KNOWN ALREADY: Success rates of medical treatment for EPL vary strongly, between but also within different treatment regimens. Up until now, although some predictors have been identified, no clinical prediction model has been developed yet. STUDY DESIGN, SIZE, DURATION: Secondary analysis of a multicentre randomized controlled trial in 17 Dutch hospitals, executed between 28 June 2018 and 8 January 2020. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women with a non-viable pregnancy between 6 and 14 weeks of gestational age, who opted for medical treatment after a minimum of 1 week of unsuccessful expectant management. Potential predictors for successful medical treatment of EPL were chosen based on literature and expert opinions. We internally validated the prediction model using bootstrapping techniques. MAIN RESULTS AND THE ROLE OF CHANCE: 237 out of 344 women had a successful medical EPL treatment (68.9%). The model includes the following variables: use of mifepristone, BMI, number of previous uterine aspirations and the presence of minor clinical symptoms (slight vaginal bleeding or some abdominal cramps) at treatment start. The model shows a moderate capacity to discriminate between success and failure of treatment, with an AUC of 67.6% (95% CI = 64.9-70.3%). The model had a good fit comparing predicted to observed probabilities of success but might underestimate treatment success in women with a predicted probability of success of ∼70%. LIMITATIONS, REASONS FOR CAUTION: The vast majority (90.4%) of women were Caucasian, potentially leading to less optimal model performance in a non-Caucasian population. Limitations of our model are that we have not yet been able to externally validate its performance and clinical impact, and the moderate accuracy of the prediction model of 0.67. WIDER IMPLICATIONS OF THE FINDINGS: We developed a prediction model, aimed to improve and personalize counselling for medical treatment of EPL by providing a woman with her individual chance of complete evacuation. STUDY FUNDING/COMPETING INTEREST(S): The Triple M Trial, upon which this secondary analysis was performed, was funded by the Healthcare Insurers Innovation Foundation (project number 3080 B15-191). TRIAL REGISTRATION NUMBER: Clinicaltrials.gov: NCT03212352.

Cost-effectiveness of diagnostic testing strategies including cervical-length measurement and fibronectin testing in women with symptoms of preterm labor.

OBJECTIVE: To evaluate the cost-effectiveness of combining cervical-length (CL) measurement and fetal fibronectin (fFN) testing in women with symptoms of preterm labor between 24 and 34 weeks' gestation. METHODS: This was a model-based cost-effectiveness analysis evaluating seven test-treatment strategies based on CL measurement and/or fFN testing in women with symptoms of preterm labor from a societal perspective, in which neonatal outcomes and costs were weighted. Estimates of disease prevalence, test accuracy and costs were based on two recently performed nationwide cohort studies in The Netherlands. RESULTS: Strategies using fFN testing and CL measurement separately to predict preterm delivery are associated with higher costs and incidence of adverse neonatal outcomes compared with strategies that combine both tests. Additional fFN testing when CL is 15-30 mm was considered cost effective, leading to a cost saving of €3919 per woman when compared with a treat-all strategy, with a small deterioration in neonatal health outcomes, namely one additional perinatal death and 21 adverse outcomes per 10 000 women with signs of preterm labor (incremental cost-effectiveness ratios €39 million and €1.9 million, respectively). Implementing this strategy in The Netherlands, a country with about 180 000 deliveries annually, could lead to an annual cost saving of between €2.4 million and €7.6 million, with only a small deterioration in neonatal health outcomes. CONCLUSION: In women with symptoms of preterm labor at 24-34 weeks' gestation, performing additional fFN testing when CL is between 15 and 30 mm is a viable and cost-saving strategy. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Fluid shift from intravascular compartment during fetal red blood cell transfusion.

OBJECTIVES: Intrauterine transfusion imposes a considerable burden on the fetal circulation by increasing volume and pressure, and a fluid shift from the fetal circulation occurs even during the procedure. The aim of this study was to quantify the intraprocedural fluid shift and to investigate the effect of procedural and fetal characteristics on this fluid shift. METHODS: In 95 alloimmunized pregnancies, we calculated fluid shift at the first intrauterine transfusion by determining initial and final blood volumes. We evaluated the association of the fluid shift with the speed and volume of the transfusion, the severity of anemia and the presence of hydrops. RESULTS: Of the included fetuses, 11 were mildly hydropic and four were severely hydropic. A mean fluid shift of 36% of the transfused volume was found. Fluid shift related positively to transfused volume (P < 0.001). The percentage fluid shift of transfused volume was inversely related to the speed of transfusion (mL/kg/min) (P < 0.041) and was not related to the severity of anemia (P = 0.55) or to hydrops (P = 0.66). It was found that younger fetuses had been unintentionally subject to high volumes and speeds of transfusion relative to their size. CONCLUSIONS: Around one-third of the transfused volume is lost from the intravascular compartment during the procedure of intrauterine transfusion. There is a large variation between fetuses, partly explained by the volume and speed of the transfusion. Neither severity of anemia nor hydrops plays a clear-cut role, and thus other factors may explain the variation in fluid shift. The probability that hematocrit will still increase after transfusion, as a result of a continuing fluid shift, should be considered in transfusion policy. Advice is given on gestational age-adjusted speed of transfusion.

The electrical heart axis in fetuses with congenital heart disease, measured with non-invasive fetal electrocardiography.

OBJECTIVES: To determine if the electrical heart axis in different types of congenital heart defects (CHD) differs from that of a healthy cohort at mid-gestation. METHODS: Non-invasive fetal electrocardiography (NI-fECG) was performed in singleton pregnancies with suspected CHD between 16 and 30 weeks of gestation. The mean electrical heart axis (MEHA) was determined from the fetal vectorcardiogram after correction for fetal orientation. Descriptive statistics were used to determine the MEHA with corresponding 95% confidence intervals (CI) in the frontal plane of all fetuses with CHD and the following subgroups: conotruncal anomalies (CTA), atrioventricular septal defects (AVSD) and hypoplastic right heart syndrome (HRHS). The MEHA of the CHD fetuses as well as the subgroups was compared to the healthy control group using a spherically projected multivariate linear regression analysis. Discriminant analysis was applied to calculate the sensitivity and specificity of the electrical heart axis for CHD detection. RESULTS: The MEHA was determined in 127 fetuses. The MEHA was 83.0° (95% CI: 6.7°; 159.3°) in the total CHD group, and not significantly different from the control group (122.7° (95% CI: 101.7°; 143.6°). The MEHA was 105.6° (95% CI: 46.8°; 164.4°) in the CTA group (n = 54), -27.4° (95% CI: -118.6°; 63.9°) in the AVSD group (n = 9) and 26.0° (95% CI: -34.1°; 86.1°) in the HRHS group (n = 5). The MEHA of the AVSD and the HRHS subgroups were significantly different from the control group (resp. p = 0.04 and p = 0.02). The sensitivity and specificity of the MEHA for the diagnosis of CHD was 50.6% (95% CI 47.5% - 53.7%) and 60.1% (95% CI 57.1% - 63.1%) respectively. CONCLUSION: The MEHA alone does not discriminate between healthy fetuses and fetuses with CHD. However, the left-oriented electrical heart axis in fetuses with AVSD and HRHS was significantly different from the control group suggesting altered cardiac conduction along with the structural defect. TRIAL REGISTRATION: Clinical trial registration number: NL48535.015.14.

Perinatal mortality and mode of delivery in monochorionic diamniotic twin pregnancies ≥ 32 weeks of gestation: a multicentre retrospective cohort study.

OBJECTIVE: To study perinatal mortality rates in a cohort of 465 monochorionic (MC) twins without twin-twin transfusion syndrome (TTS) born at 32 weeks of gestation or later since reported interauterine fetal death (IUFD) rates >32 weeks of gestations in the literature vary, leading to varying recommendations on the optimal timing of delivery, and to investigate the relation between perinatal mortality and mode of delivery. DESIGN: Multicentre retrospective cohort study. SETTING: Ten perinatal referral centres in the Netherlands. POPULATION: All MC twin pregnancies without TTTS delivered at ≥ 32 weeks of gestation between January 2000 and December 2005. METHODS: The medical records of all MC twin pregnancies without TTTS delivered at the ten perinatal referral centres in the Netherlands between January 2000 and December 2005 were reviewed. MAIN OUTCOME MEASURES: Perinatal mortality in relation to gestational age and mode of delivery at ≥ 32 weeks of gestation. RESULTS: After 32 weeks of gestation, five out of 930 fetuses died in utero and there were six neonatal deaths (6 per 1000 infants). In women who delivered ≥ 37 weeks, perinatal mortality was 7 per 1000 infants. Trial of labour was attempted in 376 women and was successful in 77%. There were three deaths in deliveries with a trial of labour (8 per 1000 deliveries), of which two were related to mode of delivery. Infants born by caesarean section without labour had an increased risk of neonatal morbidity and respiratory distress syndrome. CONCLUSIONS: In MC twin pregnancies the incidence of intrauterine fetal death is low ≥ 32 weeks of gestation. Therefore, planned preterm delivery before 36 weeks does not seem to be justified. The risk of intrapartum death is also low, at least in tertiary centres.

Fetal stress hormone changes during intrauterine transfusions.

OBJECTIVE: To document fetal stress hormone and Doppler changes after intrauterine transfusions (IUTs) in either the intrahepatic portion of the umbilical vein (IHV) or the placental cord insertion (PCI). METHOD: Pregnant women scheduled for IUT for fetal anemia (N = 25) were included prospectively. Cortisol, ß-endorphin and noradrenalin concentrations in fetal plasma and middle cerebral artery pulsatility index before and after transfusion were compared. Transfusions were performed through the (IHV), thus puncturing the fetus, or at the PCI. RESULTS: There were no measurable differences between the transfusion sites. CONCLUSION: In anemic fetuses undergoing transfusion, Doppler changes and fetal stress hormone changes were unrelated to the site of needle insertion.

Monitoring and treatment of anti-D in pregnancy.

Prophylactic anti-D is a very safe and effective therapy for the suppression of anti-D immunization and thus prevention of haemolytic disease of the foetus and newborn. However, migration from countries with low health standards and substantial cuts in public health expenses have increased the incidence of anti-D immunization in many "developed" countries. Therefore, this forum focuses on prenatal monitoring standards and treatment strategies in pregnancies with anti-D alloimmunization. The following questions were addressed, and a response was obtained from 12 centres, mainly from Europe.

Hematological characteristics in neonates with twin anemia-polycythemia sequence (TAPS).

OBJECTIVE: To evaluate the neonatal hematological features of monochorionic twins with twin anemia-polycythemia sequence (TAPS) and to determine the additional diagnostic value of reticulocyte count measurement. METHODS: A cohort of consecutive monochorionic twins with TAPS (n = 19) was included in the study and each twin pair was compared with two monochorionic twin pairs (n = 38) unaffected by TAPS or twin-twin transfusion syndrome (TTTS), matched for gestational age at birth. We measured full blood counts on day 1 and determined the incidence of anemia, polycythemia, reticulocytosis and thrombocytopenia. RESULTS: Median inter-twin hemoglobin (Hb) difference in monochorionic twins with and without TAPS was 13.7 g/dL and 2.4 g/dL, respectively (p < 0.01). Median inter-twin reticulocyte count ratio in twins with and without TAPS was 3.1 and 1.0, respectively (p < 0.01). Thrombocytopenia (platelet count < 150 x 10(9)/L) occurred more often in the TAPS group than in the control group, 45% (17/38) versus 11% (11/38), respectively (p < 0.01). In the TAPS group, mean platelet count was significantly lower in recipients than in donors, 133 x 10(9)/L versus 218 x 10(9)/L, respectively (p < 0.01). CONCLUSIONS: TAPS twins have a large inter-twin Hb difference in combination with a large inter-twin reticulocyte count ratio. Recipients are more often thrombocytopenic than donors, probably due to polycythemia.

Twin anemia-polycythemia sequence: diagnostic criteria, classification, perinatal management and outcome.

Monochorionic twins share a single placenta with intertwin vascular anastomoses, allowing the transfer of blood from one fetus to the other and vice versa. These anastomoses are the essential anatomical substrate for the development of several complications, including twin-twin transfusion syndrome (TTTS) and twin anemia-polycythemia sequence (TAPS). TTTS and TAPS are both chronic forms of fetofetal transfusion. TTTS is characterized by the twin oligopolyhydramnios sequence, whereas TAPS is characterized by large intertwin hemoglobin differences in the absence of amniotic fluid discordances. TAPS may occur spontaneously in up to 5% of monochorionic twins and may also develop after incomplete laser treatment in TTTS cases. This review focuses on the pathogenesis, incidence, diagnostic criteria, management options and outcome in TAPS. In addition, we propose a classification system for antenatal and postnatal TAPS.

Quantification of feto-fetal transfusion rate through a single placental arterio-venous anastomosis in a monochorionic twin pregnancy.

Twin-to-twin transfusion syndrome (TTTS) is due to unbalanced inter-twin blood flow through placental vascular anastomoses. We present a TTTS-case treated with fetoscopic laser surgery that allowed us to calculate the net inter-twin blood flow. In the weeks following laser treatment, the ex-recipient developed severe fetal anemia and was treated with two intrauterine adult red cell transfusions (at 26 and 29 weeks' gestation, respectively). After birth, placental injection with color-latex identified a single residual arterio-venous anastomosis from the ex-recipient to the ex-donor. We measured the fetal and adult hemoglobin concentrations in the anemic fetus before and after both intrauterine transfusions, and in both twins at birth. On the basis of these measurements, we calculated the blood flow across the residual arterio-venous anastomosis and found it to be 5.8+/-1.5 mL/24h after the 1st transfusion and 11.4+/-2.9 mL/24h after the 2nd transfusion.

Placental characteristics of monoamniotic twin pregnancies in relation to perinatal outcome.

OBJECTIVE: To study placental characteristics in relation to perinatal outcome in 55 pairs of monochorionic monoamniotic (MA) twins. METHODS: Between January 1998 and May 2008 55 pairs of MA twins were delivered in 4 tertiary care centers and analysed for mortality, birth weight discordancy and twin-to-twin transfusion syndrome (TTTS) in relation to type of anastomoses, type and distance between cord insertions and placental sharing. Five acardiac twins, 2 conjoined twins, 4 higher order multiples and one early termination of pregnancy were excluded, leaving 43 MA placentas for analysis. Of these 43, one placenta could not be analysed for placental vascular anastomoses due to severe maceration after single intra-uterine demise leaving 42 placentas for analysis of anastomoses. RESULTS: Arterio-arterial (AA), venovenous (VV) and arteriovenous (AV) anastomoses were detected in 98%, 43% and 91% of MA placentas, respectively. Velamentous cord insertion was found in 4% of cases. Small distance between both umbilical cord insertions (<5 cm) was present in 53% of MA placentas. Overall perinatal loss rate was 22% (19/86). We found no association between mortality and type of anastomoses, type and distance between cord insertions and placental sharing. The incidence of TTTS was low (2%) and occurred in the only pregnancy with absent AA-anastomoses. CONCLUSION: Perinatal mortality in MA twins was not related to placental vascular anatomy. The almost ubiquitous presence of compensating AA-anastomoses in MA placentas appears to prevent occurrence of TTTS.

Fetal brain hemodynamic changes in intrauterine transfusion: influence of needle puncture site.

OBJECTIVES: Previous research has suggested that hemodynamic changes after in utero transfusion may be related to fetal stress. We tested the hypothesis that these hemodynamic changes are more pronounced when the needle is inserted in the fetal abdomen compared with the umbilical cord root. METHODS: Most intrauterine transfusions are performed by inserting a needle either in the umbilical cord root at the placental surface (PCI) or in the intrahepatic portion of the umbilical vein (IHV). We analyzed prospectively collected data of all intrauterine blood transfusions (IUT) for fetal alloimmune anemia (from 2000 to 2003), for which complete data were available on needling site and middle cerebral artery (MCA) Doppler flow velocity measurements before and immediately after the procedure. RESULTS: Data of 57 IUTs were included. In 32 patients, the transfusion was performed through the PCI and in 25 patients through the IHV. Mean pulsatility index (PI) in the PCI group was 2.0 before and 1.7 after IUT (p = 0.011), and in the IHV group 1.9 before and 1.5 after IUT (p = 0.001). In both groups, MCA PI decreased significantly, but there was no difference in decrease between the two groups (p = 0.99). CONCLUSIONS: In anemic fetuses undergoing transfusion, the observed fetal brain hemodynamic changes were independent of the site of needle insertion. The decrease in fetal MCA PI is therefore likely to be caused by the volume expansion.

Total blood volume is maintained in nonhydropic fetuses with severe hemolytic anemia.

OBJECTIVE: Fetal alloimmune anemia is associated with increased blood flow velocities and cardiomegaly. In severe cases, hydrops can develop. We investigated whether the decrease of red blood cell volume is associated with a reduction or expansion of plasma volume. METHODS: In 86 alloimmunized fetuses that received a first intrauterine transfusion, we calculated fetal total blood volumes (i.e. fetoplacental blood volumes) using a dilutional principle of fetal hemoglobin with adult hemoglobin. The relation between total blood volume and estimated fetal weight, severity of anemia and hydrops was analyzed. RESULTS: Gestational age ranged from 17 to 35 weeks. Mean hemoglobin deficit was 6.8 standard deviations (range 2.1-11.7) below the normal mean. Fetal total blood volume was significantly related to estimated fetal weight (p < 0.001). Mean total blood volume in nonhydropic fetuses was 123 ml/kg (n = 74) and in hydropic fetuses 144 ml/kg (n = 12). There was a significant relation between total blood volume per kg body weight and hydrops (p = 0.035); however, there was no relation with severity of anemia (p = 0.94). CONCLUSION: In the human nonhydropic fetus with severe hemolytic anemia, total blood volume is maintained: the decrease in red blood cell volume is thus compensated by an increase in plasma volume. In hydropic fetuses, however, total blood volume seems to be increased. This is in accordance with the hypothesis that congestive heart failure plays a role in the pathophysiology of hydrops in anemic fetuses.

TAPS and TOPS: two distinct forms of feto-fetal transfusion in monochorionic twins.

Monochorionic twins share a single placenta with inter-twin vascular anastomoses, allowing the transfer of blood from one fetus to the other and vice versa. These anastomoses are the essential anatomical substrate for the development of severe complications, including twin-twin transfusion syndrome (TTTS) and twin-anemia-polycythemia sequence (TAPS). TTTS and TAPS are both chronic forms of feto-fetal transfusion. TTTS is characterized by the twin oligo-polyhydramnios sequence (TOPS), whereas TAPS is characterized by large inter-twin hemoglobin differences in the absence of amniotic fluid discordances. TAPS may occur spontaneously in a minority of monochorionic twins or in TTTS cases after laser treatment. This review focuses on the differences between TAPS and TTTS in terms of pathogenesis, incidence, diagnostic criteria, treatment modalities, perinatal outcome and long-term outcome.

Case report: twin-to-twin transfusion syndrome resulting from placental collateral artery development.

BACKGROUND: The twin-to-twin transfusion syndrome (TTTS) is a severe complication of monochorionic twin pregnancies, caused by a net inter-twin transfusion of blood from one fetus (the donor) towards the other fetus (the recipient) through placental anastomoses. TTTS is driven by unidirectional arterio-venous anastomoses, and mitigated by bidirectional arterio-arterial or veno-venous anastomoses which reduce the net inter-twin transfusion. In contrast to these accepted concepts, cases have been described paradoxically devoid of arterio-venous anastomoses but including arterio-arterial anastomoses. We hypothesized that TTTS may develop in such cases as a consequence of a stenosed chorionic artery in the recipient placenta that connects with the arterio-arterial anastomosis. CLINICAL CASES: We describe two cases of monochorionic twin placentae without arterio-venous anastomoses but with only an arterio-arterial and veno-venous anastomosis. In one case severe TTTS developed. There, the arterio-arterial anastomosis connected to a stenosed chorionic artery in the recipient placenta and showed a tortuous appearance. The other case developed uneventful. It lacked a stenosed chorionic artery and the arterio-arterial anastomosis was non-tortuous. CONCLUSION: We present evidence that the arterio-arterial anastomosis represented a functional collateral artery whose outgrowth was driven by an increased shear-stress caused by an increased flow to a lower pressure vascular bed in the placenta of the recipient. The lower arterial pressure occurred from the moment that a chorionic artery which was connected to the anastomosis developed a significant stenosis. The resulting collateral flow through the anastomosis maintained blood supply to the lower pressure placental bed, the beneficial function of collaterals, but also resulted in an increasing net inter-twin transfusion which triggered onset of severe TTTS.

Simulated sequential laser therapy of twin-twin transfusion syndrome.

Sequential laser therapy of twin-twin transfusion syndrome (TTTS) includes laser obliteration of arteriovenous (AV) anastomoses from donor to recipient (AVDR) before obliterating AV anastomoses from recipient to donor (AVRD). This strategy allows for a beneficial intra-operative transfusion of blood from the hypervolemic recipient to the hypovolemic donor. In the present study, we sought to analyze the benefits and risks of sequential laser therapy with our computational model to aid its more widespread introduction. We simulated an equally shared placenta with an AVDR and a smaller diameter AVRD causing TTTS at 20 weeks. Laser coagulation and various volumes and directions of inter-twin transfusion were simulated at 21 weeks. A typical result is that when an AVDR is coagulated first, and 10 min later the AVRD with inner diameter of about 1 mm, an inter-twin transfusion of 25 ml may result from the recipient to the donor, based on literature data of AV flow versus diameter. This procedure causes a simulated loss of 50% of the recipient's blood volume. The opposite coagulation sequence, thus coagulating the AVRD first, 10 min later followed by the AVDR of 1 mm inner diameter, causes a loss of the donor's blood volume of 64%. In conclusion, our simulations support the concept of sequential laser therapy for TTTS and suggest directions for an improved safety and efficacy of this strategy.

Placental characteristics in monochorionic twins with and without twin anemia-polycythemia sequence.

OBJECTIVE: To study the placental angioarchitecture of monochorionic placentas with and without twin anemia-polycythemia sequence. METHODS: Eligible were all placentas from monochorionic twin gestations, not complicated by twin-to-twin transfusion syndrome and resulting in double survival. The study was conducted at two European Fetal Therapy Centers between 2002 and 2008. Placental angioarchitecture was evaluated using colored dye injection. Diagnosis of twin anemia-polycythemia sequence was based on the presence of large intertwin hemoglobin difference without the degree of amniotic fluid discordance that is required for the diagnosis of twin transfusion syndrome. RESULTS: Three-hundred thirteen monochorionic twin pregnancies were eligible for the study but placental data could not be completed for 62 placentas (20%). This left 251 monochorionic twin pregnancies of which 11 (4%) fulfilled the criteria for twin anemia-polycythemia sequence. The median number of anastomoses in monochorionic placentas with and without twin anemia-polycythemia sequence was 3 (range: 2-5) and 7 (range: 0-25), respectively (P<.001). Small anastomoses were present in 91% (10/11) of twin anemia-polycythemia sequence-placentas compared with 5% (12/240) of cases without twin anemia-polycythemia sequence (P<.001). Arterioarterial anastomoses were absent in twin anemia-polycythemia sequence-placentas and present in 89% (213/240) of placentas without twin anemia-polycythemia sequence (P<.001). CONCLUSION: Monochorionic twin placentas with twin anemia-polycythemia sequence are characterized by a paucity of anastomoses and the absence of arterioarterial anastomoses. The few anastomoses that are present in twin anemia-polycythemia sequence placentas are mostly small arteriovenous anastomoses.

Fetoscopic laser treatment of twin-to-twin transfusion syndrome followed by severe twin anemia-polycythemia sequence with spontaneous resolution.

We present a case of twin anemia-polycythemia sequence after laser surgery for twin-to-twin transfusion syndrome which resolved spontaneously. No residual anastomoses were identified after placental injection with colored dye. We discuss the possible pathogenetic mechanisms that may have led to this remarkable clinical course and discuss the various management options.

Fetal cardiac output in monochorionic twins.

OBJECTIVES: To compare fetal cardiac output (CO) in donor and recipient twins of twin-twin transfusion syndrome (TTTS) pregnancies after laser therapy with that of monochorionic twins without TTTS and normal singletons. METHODS: In a longitudinal, prospective study, we sonographically assessed fetal CO in donors (n = 10) and recipients (n = 10) with TTTS after fetoscopic laser therapy, in monochorionic twins without TTTS (n = 20) and in normal singleton pregnancies (n = 20). The fetal CO of TTTS twins was determined 1 day and 1 week after laser treatment, and from then on every 2-4 weeks until birth. Twins without TTTS were examined biweekly until birth. Singletons were examined twice, with an 8-week interval, at different gestational ages between 17 and 35 weeks. RESULTS: Absolute CO increased exponentially with advancing gestational age (P < 0.0001), and was significantly related to fetal weight in all groups (P < 0.0001). The median CO/kg in donors after laser therapy, recipients after laser therapy and non-TTTS monochorionic twins was significantly higher than that in singletons (all P < 0.001). Median CO/kg in donors after laser therapy, recipients after laser therapy, and non-TTTS monochorionic twins was not significantly different between groups. CONCLUSIONS: Monochorionic twins with TTTS have higher CO after laser therapy than normal singletons.

Biochemical composition of fluids for amnioinfusion during fetoscopy.

OBJECTIVE: To evaluate which of the commercially available solutions is best suited for amnioinfusion during fetoscopy, based on resemblance with the biochemical properties of amniotic fluid. MATERIALS AND METHODS: Amniotic fluid samples from 10 pregnancies were studied. Specimens were obtained from 5 pathologic pregnancies (of which 3 were complicated by polyhydramnios) and 5 uncomplicated pregnancies. The concentrations of sodium, potassium, chloride, bicarbonate, calcium, glucose, osmolality, pH, total protein content and albumin were determined in each sample. A literature search (PubMed, Embase) was performed to identify commercially available fluids used for amnioinfusion in clinical practice. The composition of these infusion solutions was compared to the amniotic fluid samples mentioned above. RESULTS: We identified two different electrolyte solutions used in clinical practice for amnioinfusion. We identified four additional commercially available solutions that could potentially be used for amnioinfusion. Most of these infusion solutions differ considerably from midtrimester amniotic fluid samples both in electrolyte composition and pH, with the most striking difference in the latter. CONCLUSION: Lactated Ringer's solution approximates amniotic fluid the closest for both electrolyte composition and pH. This infusion solution seems to be the most suitable choice for amnioinfusion during fetoscopy.