Fetal Medicine Foundation charts for fetal growth in twins.

OBJECTIVE: To derive reference distributions of estimated fetal weight (EFW) in twins relative to singletons. METHODS: Gestational-age- and chorionicity-specific reference distributions for singleton percentiles and EFW were fitted to data on 4391 twin pregnancies with two liveborn fetuses from four European centers, including 3323 dichorionic (DC) and 1068 monochorionic diamniotic (MCDA) twin pregnancies. Gestational age was derived using the larger of the two crown-rump length measurements obtained during the first trimester of pregnancy. EFW was obtained from ultrasound measurements of head circumference, abdominal circumference and femur length using the Hadlock formula. Singleton percentiles were obtained using the Fetal Medicine Foundation population weight charts for singleton pregnancies. Hierarchical models were fitted to singleton Z-scores with autoregressive terms for serial correlations within the same fetus and between twins from the same pregnancy. Separate models were fitted for DC and MCDA twins. RESULTS: Fetuses from twin pregnancies tended to be smaller than singletons at the earliest gestational ages (16 weeks for MCDA and 20 weeks for DC twins). This was followed by a period of catch-up growth until around 24 weeks. After that, both DC and MCDA twins showed reduced growth. In DC twins, the EFW corresponding to the 50th percentile was at the 50th percentile of singleton pregnancies at 23 weeks, the 43rd percentile at 28 weeks, the 32nd percentile at 32 weeks and the 22nd percentile at 36 weeks. In MCDA twins, the EFW corresponding to the 50th percentile was at the 36th percentile of singleton pregnancies at 24 weeks, the 29th percentile at 28 weeks, the 19th percentile at 32 weeks and the 12th percentile at 36 weeks. CONCLUSIONS: In DC and, to a greater extent, MCDA twin pregnancies, fetal growth is reduced compared with that observed in singleton pregnancies. Furthermore, after 24 weeks, the divergence in growth trajectories between twin and singleton pregnancies becomes more pronounced as gestational age increases. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Risk of fetal loss after chorionic villus sampling in twin pregnancy derived from propensity score matching analysis.

OBJECTIVE: To estimate the risk of fetal loss associated with chorionic villus sampling (CVS) in twin pregnancy, using propensity score analysis. METHODS: This was a multicenter cohort study of women with twin pregnancy undergoing ultrasound examination at 11-13 weeks' gestation, performed in eight fetal medicine units in which the leadership were trained at the Harris Birthright Research Centre for Fetal Medicine in London, UK, and in which the protocols for screening, invasive testing and pregnancy management are similar. The risk of death of at least one fetus was compared between pregnancies that had and those that did not have CVS, after propensity score matching (1:1 ratio). This procedure created two comparable groups by balancing the maternal and pregnancy characteristics that lead to CVS being performed, similar to how randomization operates in a randomized clinical trial. RESULTS: The study population of 8581 twin pregnancies included 445 that had CVS. Death of one or two fetuses at any stage during pregnancy occurred in 11.5% (51/445) of pregnancies in the CVS group and in 6.3% (515/8136) in the non-CVS group (P < 0.001). The propensity score algorithm matched 258 cases that had CVS with 258 non-CVS cases; there was at least one fetal loss in 29 (11.2%) cases in the CVS group and in 35 (13.6%) cases in the matched non-CVS group (odds ratio (OR), 0.81; 95% CI, 0.48-1.35; P = 0.415). However, there was a significant interaction between the risk of fetal loss after CVS and the background risk of fetal loss; when the background risk was higher, the risk of fetal loss after CVS decreased (OR, 0.46; 95% CI, 0.23-0.90), while, in pregnancies with a lower background risk of fetal loss, the risk of fetal loss after CVS increased (OR, 2.45; 95% CI, 0.95-7.13). The effects were statistically significantly different (P-value of the interaction = 0.005). For a pregnancy in which the background risk of fetal loss was about 6% (the same as in our non-CVS population), there was no change in the risk of fetal loss after CVS, but, when the background risk was more than 6%, the posterior risk was paradoxically reduced, and when the background risk was less than 6%, the posterior risk increased exponentially; for example, if the background risk of fetal loss was 2.0%, the relative risk was 2.8 and the posterior risk was 5.6%. CONCLUSION: In twin pregnancy, after accounting for the risk factors that lead to both CVS and spontaneous fetal loss and confining the analysis to pregnancies at lower prior risk, CVS seems to increase the risk of fetal loss by about 3.5% above the patient's background risk. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Fetal loss after chorionic villus sampling in twin pregnancy.

OBJECTIVE: To estimate the chorionic villus sampling (CVS)-related risk of fetal loss in twin pregnancy after adjustment for chorionicity, nuchal translucency thickness (NT), intertwin discordance in crown-rump length (CRL), maternal demographic characteristics and serum pregnancy-associated plasma protein-A (PAPP-A) and free ß-human chorionic gonadotropin (ß-hCG). METHODS: This was a multicenter study from eight fetal medicine units in which the leadership were trained at the Harris Birthright Research Centre for Fetal Medicine in London, UK, and in which the protocols for screening, invasive testing and pregnancy management are similar. Data were obtained prospectively from women with twin pregnancy undergoing routine ultrasound examination at 11-13 weeks' gestation. Multivariable logistic regression analysis with backward stepwise elimination was used to examine whether CVS provided a significant independent contribution to the prediction of risk of fetal loss after adjusting for maternal and pregnancy characteristics, including maternal age, racial origin and weight, method of conception, smoking status, parity, chorionicity, intertwin discordance in CRL, fetal NT ≥ 95th percentile and free ß-hCG and PAPP-A multiples of the median. Similarly, within the CVS group, multivariable logistic regression analysis was used to investigate the effect of the number of intrauterine needle insertions and size of the needle on the risk of fetal loss. RESULTS: The study population of 8581 twin pregnancies undergoing ultrasound examination at 11-13 weeks' gestation included 316 dichorionic and 129 monochorionic twins that had CVS. First, in twin pregnancies undergoing CVS, compared to those not undergoing CVS, there was a 2-fold increased risk of fetal loss at < 24 weeks' gestation and of loss at any stage in pregnancy. Second, the factors providing a significant independent contribution to the prediction of miscarriage or fetal loss in twin pregnancy were increased maternal weight, black racial origin, monochorionicity, and more so monoamnionicity, large intertwin discordance in CRL and increased fetal NT, and, in the case of fetal loss at any stage, there was also a contribution from assisted conception and low serum PAPP-A. Third, after adjustment for maternal and pregnancy characteristics, CVS did not provide a significant contribution to the risk of fetal loss. Fourth, in twin pregnancies that had CVS, there was no significant contribution to fetal loss from the number of intrauterine needle insertions or needle size. CONCLUSION: The 2-fold increased risk of fetal loss following CVS in twin pregnancy can, to a great extent, be explained by maternal and pregnancy characteristics rather than the invasive procedure itself. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Prediction of pre-eclampsia in twin pregnancy by maternal factors and biomarkers at 11-13 weeks' gestation: data from EVENTS trial.

OBJECTIVES: First, to validate a previously developed model for screening for pre-eclampsia (PE) by maternal characteristics and medical history in twin pregnancies; second, to compare the distributions of mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), serum placental growth factor (PlGF) and serum pregnancy-associated plasma protein-A (PAPP-A) in twin pregnancies that delivered with PE to those in singleton pregnancies and to develop new models based on these results; and, third, to examine the predictive performance of these models in screening for PE with delivery at < 32 and < 37 weeks' gestation. METHODS: Two datasets of prospective non-intervention multicenter screening studies for PE in twin pregnancies at 11 + 0 to 13 + 6 weeks' gestation were used. The first dataset was from the EVENTS (Early vaginal progesterone for the preVention of spontaneous prEterm birth iN TwinS) trial and the second was from a previously reported study that examined the distributions of biomarkers in twin pregnancies. Maternal demographic characteristics and medical history from the EVENTS-trial dataset were used to assess the validity of risks from our previously developed model. The combined data from the first and second datasets were used to compare the distributional properties of log10 multiples of the median (MoM) values of UtA-PI, MAP, PlGF and PAPP-A in twin pregnancies that delivered with PE to those in singleton pregnancies and develop new models based on these results. The competing-risks model was used to estimate the individual patient-specific risks of delivery with PE at < 32 and < 37 weeks' gestation. Screening performance was measured by detection rates (DR) and areas under the receiver-operating-characteristics curve. RESULTS: The EVENTS-trial dataset comprised 1798 pregnancies, including 168 (9.3%) that developed PE. In the validation of the prior model based on maternal characteristics and medical history, calibration plots demonstrated very good agreement between the predicted risks and the observed incidence of PE (calibration slope and intercept for PE < 32 weeks were 0.827 and 0.009, respectively, and for PE < 37 weeks they were 0.942 and -0.207, respectively). In the combined data, there were 3938 pregnancies, including 339 (8.6%) that developed PE and 253 (6.4%) that delivered with PE at < 37 weeks' gestation. In twin pregnancies that delivered with PE, MAP, UtA-PI and PlGF were, at earlier gestational ages, more discriminative than in singleton pregnancies and at later gestational ages they were less so. For PAPP-A, there was little difference between PE and unaffected pregnancies. The best performance of screening for PE was achieved by a combination of maternal factors, MAP, UtA-PI and PlGF. In screening by maternal factors alone, the DR, at a 10% false-positive rate, was 30.6% for delivery with PE at < 32 weeks' gestation and this increased to 86.4% when screening by the combined test; the respective values for PE < 37 weeks were 24.9% and 41.1%. CONCLUSIONS: In the assessment of risk for PE in twin pregnancy, we can use the same prior model based on maternal characteristics and medical history as reported previously, but in the calculation of posterior risks it is necessary to use the new distributions of log10 MoM values of UtA-PI, MAP and PlGF according to gestational age at delivery with PE. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

New approach for estimating risk of miscarriage after chorionic villus sampling.

OBJECTIVE: To estimate the risk of miscarriage associated with chorionic villus sampling (CVS). METHODS: This was a retrospective cohort study of women attending for routine ultrasound examination at 11 + 0 to 13 + 6 weeks' gestation at one of eight fetal-medicine units in Spain, Belgium and Bulgaria, between July 2007 and June 2018. Two populations were included: (1) all singleton pregnancies undergoing first-trimester assessment at Hospital Clínico Universitario Virgen de la Arrixaca in Murcia, Spain, that did not have CVS (non-CVS group); and (2) all singleton pregnancies that underwent CVS following first-trimester assessment at one of the eight participating centers (CVS group). We excluded pregnancies diagnosed with genetic anomalies or major fetal defects before or after birth, those that resulted in termination and those that underwent amniocentesis later in pregnancy. We used propensity score (PS) matching analysis to estimate the association between CVS and miscarriage. We compared the risk of miscarriage of the CVS and non-CVS groups after PS matching (1:1 ratio). This procedure creates two comparable groups balancing the maternal and pregnancy characteristics that are associated with CVS, in a similar way to that in which randomization operates in a randomized clinical trial. RESULTS: The study population consisted of 22 250 pregnancies in the non-CVS group and 3613 in the CVS group. The incidence of miscarriage in the CVS group (2.1%; 77/3613) was significantly higher than that in the non-CVS group (0.9% (207/22 250); P < 0.0001). The PS algorithm matched 2122 CVS with 2122 non-CVS cases, of which 40 (1.9%) and 55 (2.6%) pregnancies in the CVS and non-CVS groups, respectively, resulted in a miscarriage (odds ratio (OR), 0.72 (95% CI, 0.48-1.10); P = 0.146). We found a significant interaction between the risk of miscarriage following CVS and the risk of aneuploidy, suggesting that the effect of CVS on the risk of miscarriage differs depending on background characteristics. Specifically, when the risk of aneuploidy is low, the risk of miscarriage after CVS increases (OR, 2.87 (95% CI, 1.13-7.30)) and when the aneuploidy risk is high, the risk of miscarriage after CVS is paradoxically reduced (OR, 0.47 (95% CI, 0.28-0.76)), presumably owing to prenatal diagnosis and termination of pregnancies with major aneuploidies that would otherwise have resulted in spontaneous miscarriage. For example, in a patient in whom the risk of aneuploidy is 1 in 1000 (0.1%), the risk of miscarriage after CVS will increase to 0.3% (0.2 percentage points higher). CONCLUSIONS: The risk of miscarriage in women undergoing CVS is about 1% higher than that in women who do not have CVS, although this excess risk is not solely attributed to the invasive procedure but, to some extent, to the demographic and pregnancy characteristics of the patients. After accounting for these risk factors and confining the analysis to low-risk pregnancies, CVS seems to increase the risk of miscarriage by about three times above the patient's background risk. Although this is a substantial increase in relative terms, in pregnancies without risk factors for miscarriage, the risk of miscarriage after CVS remains low and similar to, or slightly higher than, that in the general population. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Nuevo enfoque para estimar el riesgo de aborto después de una biopsia de vellosidades coriónicas OBJETIVO: Estimar el riesgo de aborto asociado con la biopsia de vellosidades coriónicas (BVC). MÉTODOS: Se trata de un estudio retrospectivo de cohorte de mujeres que acudieron a un examen ecográfico de rutina entre las 11+0 y las 13+6 semanas de gestación a una de entre un total de ocho centros de medicina fetal en España, Bélgica y Bulgaria, entre julio de 2007 y junio de 2018. En el estudio se incluyeron dos poblaciones: 1) todos los embarazos con feto único sometidos a evaluación del primer trimestre en el Hospital Clínico Universitario Virgen de la Arrixaca de Murcia (España), a las que no se les hizo una BVC (grupo no BVC); y 2) todos los embarazos con feto único sometidos a BVC tras la evaluación del primer trimestre en uno de los ocho centros participantes (grupo BVC). Se excluyeron los embarazos diagnosticados con anomalías genéticas o defectos fetales importantes antes o después del nacimiento, los que resultaron en una interrupción y los que más tarde se sometieron a amniocentesis durante el embarazo. Para estimar la relación entre la BVC y el aborto espontáneo se utilizó el pareamiento por puntaje de propensión (PPP). Se comparó el riesgo de aborto de los grupos BVC y no BVC después del pareamiento PPP (razón 1:1). Este procedimiento creó dos grupos comparables en los que las características de la madre y el embarazo que se asocian con la BVC estaban equilibradas, de manera similar a cómo funciona la aleatorización en un ensayo clínico aleatorizado. RESULTADOS: La población de estudio consistió en 22.250 embarazos en el grupo no BVC y 3.613 en el grupo BVC. La incidencia de abortos en el grupo BVC (2,1%; 77/3.613) fue significativamente mayor que en el grupo no BVC (0,9% (207/22.250); P<0,0001). El algoritmo del PPP emparejó 2.122 BVC con 2.122 casos no BVC, de los cuales 40 (1,9%) y 55 (2,6%) embarazos en los grupos BVC y no BVC, respectivamente, resultaron en un aborto espontáneo (razón de momios (RM), 0,72 (IC 95%, 0,48-1,10); P=0,146). Se encontró una interacción significativa entre el riesgo de aborto espontáneo después de una BVC y el riesgo de aneuploidía, lo que sugiere que el efecto de la BVC en el riesgo de aborto espontáneo difiere según las características del contexto. Concretamente, cuando el riesgo de aneuploidía es bajo, el riesgo de aborto después de una BVC aumenta (RM, 2,87 (IC 95%, 1,13-7,30)) y cuando el riesgo de aneuploidía es alto, paradójicamente el riesgo de aborto después de una BVC se reduce (RM, 0,47 (IC 95%, 0,28-0,76)), presumiblemente debido al diagnóstico prenatal y a la interrupción de embarazos con aneuploidías importantes que, de otro modo, hubieran provocado un aborto espontáneo. Por ejemplo, en una paciente para quien el riesgo de aneuploidía es de 1 entre 1000 (0,1%), el riesgo de aborto después de la BVC aumenta al 0,3% (0,2 puntos porcentuales más alto). CONCLUSIONES: El riesgo de aborto espontáneo en las mujeres que se someten a una BVC es aproximadamente un 1% mayor que el de las mujeres a las que no se les hace, aunque este exceso de riesgo no se atribuye únicamente al procedimiento agresivo sino, en cierta medida, a las características demográficas y del embarazo de cada paciente. Después de tener en cuenta estos factores de riesgo y limitar el análisis a los embarazos de bajo riesgo, la BVC parece triplicar aproximadamente el riesgo de aborto en comparación con el riesgo de fondo de la paciente. Aunque se trata de un aumento sustancial en términos relativos, en los embarazos sin factores de riesgo de aborto, después de una BVC el riesgo de aborto sigue siendo bajo y similar, o ligeramente superior, al de la población en general. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

First-trimester screening for trisomies in pregnancies with vanishing twin.

OBJECTIVES: To examine multiples of the median (MoM) values of serum free beta-human chorionic gonadotropin (ß-hCG) and pregnancy-associated plasma protein-A (PAPP-A) in a large series of pregnancies with a vanishing twin, determine the association of these values with the interval between embryonic death and blood sampling, and develop a model that would allow incorporation of these metabolites in first-trimester combined screening for trisomy. METHODS: This was a retrospective study comparing maternal serum free ß-hCG and PAPP-A levels at 11-13 weeks' gestation in 528 dichorionic pregnancies with a vanishing twin, including 194 (36.7%) with an empty gestational sac and 334 (63.3%) with a dead embryo, with those in 5280 normal singleton pregnancies matched for method of conception and date of examination. In vanishing-twin pregnancies with a dead embryo, marker levels were examined in relation to the estimated time between embryonic death and maternal blood sampling. RESULTS: First, in pregnancies with a vanishing twin, median free ß-hCG MoM was not significantly different from that in normal singleton pregnancies (1.000; 95% CI, 0.985-1.016 vs 0.995; 95% CI, 0.948-1.044; P = 0.849). Second, PAPP-A MoM was higher in vanishing-twin pregnancies than in normal singleton pregnancies (1.000; 95% CI, 0.985-1.015), both in the group with an empty gestational sac (1.165; 95% CI, 1.080-1.256; P = 0.0001) and in that with a dead embryo (1.175; 95% CI, 1.105-1.249; P < 0.0001). Third, in vanishing-twin pregnancies with a dead embryo, PAPP-A MoM was related inversely to the interval between estimated gestational age at embryonic demise and blood sampling (P < 0.0001). Fourth, in first-trimester screening for trisomy 21 in singleton pregnancies, the estimated detection rate, at a 5% false-positive rate, was 82% in screening by a combination of maternal age and fetal nuchal translucency thickness, and this increased to 86% with the addition of serum free ß-hCG and to 91% with the addition of serum PAPP-A. Fifth, similar performance of screening can be achieved in pregnancies with a vanishing twin, provided the appropriate adjustments are made to the level of PAPP-A for the interval between estimated gestational age at embryonic demise and blood sampling. CONCLUSIONS: First-trimester screening for trisomy in pregnancies with a vanishing twin should rely on a combination of maternal age, fetal nuchal translucency thickness and serum free ß-hCG, as in singleton pregnancy, without the use of serum PAPP-A. Alternatively, PAPP-A can be included but only after appropriate adjustment for the interval between estimated gestational age at fetal demise and blood sampling. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Revised competing-risks model in screening for pre-eclampsia in twin pregnancy by maternal characteristics and medical history.

BACKGROUND: We have proposed previously that the competing-risks model for prediction of pre-eclampsia (PE) based on maternal characteristics and medical history (prior model), developed in singleton pregnancies, can be extended to risk assessment for twins; in dichorionic (DC) and monochorionic (MC) twin pregnancies with the same characteristics as in singleton pregnancies, the distribution of gestational age at delivery with PE was shifted to the left by 8 and 10 weeks, respectively. However, in a subsequent validation study, we found that, in both the training and validation datasets, the observed incidence of PE was lower than the predicted one and such overestimation of risk was particularly marked for early PE. OBJECTIVES: First, to develop a new extension of the competing-risks prior model in screening for PE by maternal demographic characteristics and medical history in twin pregnancies in a training dataset. Second, to examine the predictive performance of this model in screening for PE with delivery < 34 weeks (early PE), < 37 weeks (preterm PE) and at any gestational age (all PE) in twins in a validation dataset. Third, to demonstrate the application of screening in a mixed population of singleton and twin pregnancies. METHODS: The data for this study were obtained from two prospective non-intervention multicenter screening studies for PE in twin pregnancies at 11 + 0 to 13 + 6 weeks' gestation. The training and validation datasets consisted of 2219 and 2999 women, respectively. We used the training dataset to fit a model in which the effect of twins on shifting the distribution of gestational age at delivery with PE in singletons to the left should not be the same for all gestational ages but the shift should depend on the singleton prior mean; the effect increases with increasing prior mean. We examined the predictive performance of the model in the training and validation datasets using the area under the receiver-operating characteristics curve (AUC) and calibration plots. Data on 16 747 singleton pregnancies obtained from the Screening ProgRamme for prE-Eclampsia (SPREE) study were included to examine the performance of screening in a mixed population of singleton and twin pregnancies. RESULTS: Calibration plots and calibration intercept and slope demonstrate superior predictive performance of the new model in the validation dataset. Although the AUC for twin pregnancies is lower than in singleton pregnancies, performance of screening in a mixed population of singleton and twin pregnancies is superior to that in singletons (AUC of 0.790 in a mixed population comprising 2% twins and 98% singletons compared to 0.775 in singletons). For the risk cut-offs likely to be used in practice, all twin pregnancies screen positive using maternal characteristics and medical history. CONCLUSIONS: A new competing-risks model in screening for PE by maternal risk factors in twin pregnancy has been developed and, using this model, the predicted risks for early PE, preterm PE and all PE are in relatively good agreement with the observed incidence of the disease. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Validation of competing-risks model in screening for pre-eclampsia in twin pregnancy by maternal factors.

OBJECTIVE: To examine the predictive performance of the competing-risks model in screening for pre-eclampsia (PE) by maternal demographic characteristics and medical history in twin pregnancy, in a training dataset used for development of the model and a validation dataset. METHODS: The data for this study were derived from two prospective non-intervention multicenter screening studies for PE in twin pregnancies at 11 + 0 to 13 + 6 weeks' gestation. The first study of 2219 women, which was reported previously, was used to develop the competing-risks model for prediction of PE and is therefore considered to be the training set. The validation study comprised 2999 women. Patient-specific risks of delivery with PE at < 34 (early), < 37 (preterm) and < 41 + 3 (all) weeks' gestation were calculated using the competing-risks model and the performance of screening for PE in the training and validation datasets was assessed. We examined the predictive performance of the model by, first, its ability to discriminate between the PE and no-PE groups using the area under the receiver-operating characteristics curve (AUC) and, second, calibration, which assesses agreement between the predicted risk and observed incidence of PE. RESULTS: The incidence of early PE, preterm PE and all PE in the training and validation datasets was similar (1.8% vs 1.4%, 5.6% vs 5.6% and 7.7% vs 7.2%, respectively) and this was substantially higher than in our previous studies in singleton pregnancies. The training and validation datasets had similar AUCs for early PE (0.670 (95% CI, 0.593-0.747) vs 0.677 (95% CI, 0.594-0.760)), preterm PE (0.666 (95% CI, (0.617-0.715) vs 0.652 (95% CI, 0.609-0.694)) and all PE (0.656 (95% CI, 0.615-0.697) vs 0.644 (95% CI, 0.606-0.682)). Calibration plots of the predictive performance of the competing-risks model demonstrated that, in both the training and validation datasets, the observed incidence of PE was lower than the predicted one and such overestimation of risk was particularly marked for early PE. CONCLUSIONS: Discrimination and calibration of the competing-risks model for PE in a validation dataset are consistent with those in the training dataset. However, the model needs to be adjusted to correct the observed overestimation of risk for early PE. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Intrafetal laser ablation for embryo reduction from dichorionic triplets to dichorionic twins.

OBJECTIVE: To report the outcome of dichorionic (DC) triplet pregnancies reduced to DC twins by laser ablation of the pelvic vessels of one of the monochorionic (MC) twins. METHODS: Intrafetal laser embryo reduction (ER) from DC triplets to DC twins was carried out in 61 pregnancies at 11 + 0 to 14 + 3 weeks' gestation. Pregnancy outcome was examined. RESULTS: Intrafetal laser was successfully carried out in all cases, but ultrasound examination within 2 weeks of the procedure demonstrated that the MC cotwin had died in 28 (45.9%) cases and was alive in the other 33 (54.1%). In the DC group, there was one miscarriage at 23 weeks, one neonatal death after delivery at 26 weeks and in the other 31 cases there were two live births at a median gestational age of 35.3 (range, 30.4-38.4) weeks. In the 28 cases in which both MC fetuses died, there was one miscarriage at 16 weeks and in the other 27 cases the separate triplet was liveborn at a median gestation of 38.2 (range, 32.2-42.1) weeks. The overall rate of miscarriage was 3.3% (2/61) and that of preterm birth (PTB) at < 33 weeks was 6.8% (4/59). CONCLUSIONS: In the management of DC triplet pregnancies, ER to DC twins by intrafetal laser ablation is associated with lower rates of miscarriage or early PTB, compared with expectant management or ER by fetal intracardiac injection of potassium chloride. However, about half of the pregnancies result in the birth of one rather than two babies. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

[CLINICAL IMPLEMENTATION OF CELL-FREE DNA ANALYSIS IN MATERNAL BLOOD IN SCREENING FOR ANEUPLOIDIES IN SINGLETON PREGNANCIES].

OBJECTIVE: Clinical implementation of cell free(cf) DNA testing in maternal blood for aneuploidies in singleton pregnancies. METHODS: This is a retrospective study conducted in two centers for fetal medicine in Sofia, Bulgaria, between October 2013 and August 2015. We examined the clinical implementation of cf DNA testing in the routine practice for trisomies 21, 18 and13 after the performance of the first trimester combined test, second trimester biochemical test and/or the combination between first and second trimester integrated test. RESULTS: Cell-free DNA testing was performed in 170 singleton pregnancies with a median maternal age of 35 (range 22-46) years. The primary risk assessment for aneuploidies was derived from 95 cases after the first trimester combined screening test, 39 cases after the second trimester biochemical screening test, 16 cases after the integrated screening test and 20 cases there were no screening test performed. The results from the first line screening test were : 8 pregnancies with risk for trisomy 21 > 1: 100; 23 pregnancies with risk for trisomy 21 from 1:100 to 1: 300; 43 pregnancies with risk for trisomy 21 from 1:300 to 1:1000 and 76 pregnancies with risk for trisomy 21 < 1: 1000. No pregnancies with high risk for T13/T18 were identified. The analysis of cf DNA in the maternal blood reported 3 cases with T21 and no cases with T18 or T13. There was only one case of T21 in the group with risk >1:100 identified by the cf DNA analysis which was also identified by the first trimester combined screening test. The positive results were confirmed with invasive testing: CVS in the first trimester (one case) and Amniocentesis in the second trimester (two cases). CONCLUSION: Clinical implementation of cell-free DNA analysis in the contingent policy for screening could improve the detection rate for T21 and could reduce the rate of invasive procedures.

[FETAL THERAPY: INTRAUTERINE THORACO-AMNIOTIC SHUNTING IN MACROCYSTIC TYPE CYSTIC ADENOMATOID MALFORMATION OF THE LUNG: REVIEW OF THE LITERATURE AND CASE REPORT].

ABSTRACT OBJECTIVE: To present a case of macrocystic type cystic adenomatoid malformation of the lung (CCAM) treated with thoraco-amniotic shunt and to review the published data to evaluate the efficiency of thoraco-amniotic shunts for drainage of (CCAM). MATERIALS AND METHODS: This wass case reported of a fetus with a large thoracic cyst, major mediastinal shift and polyhidramnion treated with thoraco-amniotic shunting. We identified 8 cases diagnosed with CCAM and only one case met the criteria for fetal surgery. Thoracoamniotic shunting was successfully performed under local anesthesia and ultrasound control with operating time of 35 minutes. Medline was searched to identify cases of CCAM treated by thoraco-amniotic shunting. RESULTS: Fetal therapy forlung lesion was successfully performed at 30 weeks of gestation with CCAM volume ratio > 1.6 January, 2015 and amniodrenage after the procedure was carried out. The pregnancy has progressed uneventfully and planned Cesarean section was performed at 38 weeks of gestation. The optimal management of such case was performed for the first time in Bulgaria, which required an experienced interdisciplinary team. The newborn underwent resection of the lesion with no growth or neurodevelopment delay. The literature search identified cases with CCAM treated with thoraco-amniotic shunting between 1987 and 2016 and the the survival rate of non-hydropic fetuses that underwent treatment was 88%. CONCLUSIONS: Thoraco-amniotic shunting for macrocystic type CCAM is associated reduced risk of fetal intrauterine death and is also likely to be beneficial for the following major postnatal surgery

[LAPAROSCOPIC TREATMENT OF PRIMARY ABDOMINAL PREGNANCY: A CASE REPORT AND REVIEW OF THE LITERATURE].

Abdominal pregnancies are 1.4% of all ectopic pregnancies. They are mostly complicated and usually managed by laparotomy, but laparoscopy is an alternative method which some surgeons perform instead of laparotomy, especially in early pregnancy. We reported a 29 year old woman with supra pubic pain and vaginal bleeding. After sonographic evaluations, ectopic pregnancy was diagnosed and the patient underwent laparoscopic surgery for termination of pregnancy. Laparoscopy is a successful alternative method of surgery for abdominal pregnancies in first trimester.

[Ultrasound Examination and Management of Twin Pregnancy.]

Twin pregnancies are found in about 3 % of all pregnancies and 2/3 are dizygotic and 1/3 are monozygotic. In the last 30 years after the introduction of assisted conception and increasing maternal age the rate of twin pregnancies dramatically increased. Compared to singletons, twins have more complications such as intrauterine demise, intrauterine selective fetal growth reStriction, congenital anomalies, miscarriage and preterm labour. Monochorionic twins are at high risk for unique complications because of blood exchange through vascular communications in the shared placenta. Twin pregnancies should be considered as a high risk pregnancies and the well-being of the two fetuses should be taken into account with a strict protocol for follow up and management options. CONCLUSION: Ultrasound examination olavs a maior role in fetal surveillance.

[Intrauterine Fetal Growth Restriction- Screening Model. Literature Review.]

Placental dysfunction is involved in a spectrum of obs.tetric conditions including preeclampsia, placental abrution and intrauterine fetal growth restriction. Their timely and accurate recognition is often a chalange since diagnostic criteria are dill based on nonspecific signs and symptomes. Fetal growth restriction (FGR) refers to a fetus that has failed to achieve its genetically determined growth potential and affects up to 5-10% of pregnancies. FRR is associated with an increase in perinatal mortality and morbidity. The diagnoslic challenge is in distinguishing SGA pregnancies from FGR pregnancies because the majority of SGA pregnancies are associated with a good prognosis compared to FGR pregnancies. Multifetal gegations have a high incidence of FGR. About 20-30% of dichorionic twins will suffer from FGR, as will 40% of monochorionic twins. Ultrasound is the benchmark for accurate pregnancy dating and diagnosis of FGR. However, there is room for error and FGR is undetected in about 30% of routinely scanned cases and incorrectly detected in 50% of cases. In recent years, the main priority of the leading obstetric clinics in Europe and the USA is drafting a universal screening model for selecting patients at high risk of developing placental dysfunction. Now, this model is part of the standard screening for chromosomal aneuploidies in the firs and second trimester of pregnancy and prolonged screening in the second and third trimester in patients at high risk.

[SECOND STAGE IN MINIINVASIVE FETAL SURGERY FOR SEVERE CONGENITAL DIAPHRAGMATIC HERNIA. CASE REPORT].

We present a case of miniinvasive fetal surgery for CDH treated at 28 and 34 weeks of gestation. The first step was successfully performed at 28 weeks with Fetal Endoscopic Tracheal Occlusion with ballon. The second step was performed at 34 weeks for balloon removal. The necessity of fetal cytogenetic assessment and array CGH was carried out to exclude gene disorders that could lead to poor long-term outcome. A planned SC and optimal neonatology management were followed by a surgical operation of the newborn. Experienced interdisciplinary team successfully provide a perinatal and postnatal surgery for severe CDH. The newborn was discharged from the hospital 3 weeks after the repairing operation in a good condition.

[Prenatal diagnosis and fetoscopic tracheal occlusion (FETO) for severe congenital diaphragmatic hernia. Case report].

We present a case of severe isolated congenital diaphragmatic hernia (CDH) diagnosed at 19 weeks of gestation and treated at 28 weeks with Fetal Endoscopic Tracheal Occlusion (FETO). The CDH was left-sided with part of the liver in the thorax and lung area to head circumference ratio (LHR) of 0.9. The FETO was successfully performed under spinal anesthesia. The pregnancy is progressing uneventfully and ultrasound examination 10 days after the FETO demonstrated an increased LHR to 1.1. Treatment with FETO for severe CDH has been performed for the first time in Bulgaria and this procedure addressed several questions for optimal management by an experienced interdisciplinary team.

[New screening method for aneuploidies based on analysis of cell-free DNA in the maternal blood].

UNLABELLED: The national program of screening for aneuploidies in Bulgaria is based on first trimester combined test, second trimester biochemical test and/or the combination between first and second trimester integrated test. OBJECTIVE: To review the literature for studies analyzing cell-free (cf) DNA in the maternal blood and to report the clinical implementation and validation of the method in the clinical practice. Literature search and study selection extracted studies since 2011 when the first article was published. The data source included searches from PubMed and Medline. The reported results for detection rates (DR) and false positive rates (FPR) in singleton pregnancies were about 99.0% and 0.08% respectively, for trisomy 21, 96.8% and 0.15% for trisomy 18, 92.1% and 0.20% for trisomy 13, 88.6% and 0.12% for monosomy X. For twin pregnancies, the DR was 94.4% and FPR was 0% for trisomy 21. CONCLUSION: Analysis of cell-free DNA in the maternal blood is an effective method of screening for aneuploidies.

[THE GESTATIONAL DIABETES MELLITUS AS A SPECIFIC PREGNANCY STATE].

Pregnancy is a condition which result in a significant changes in the course of the metabolic processes in woman's body. The impairments in the carbohydrate metabolism, in particular Gestational Diabetes mellitus are the most frequent observed during pregnancy. Extremely important for the clinician is to knows the risk factors, which can predispose to the appearance of these disorders, and in time to explores the patients. This allows to avoid both early and late complications for the mother and her future child.

[THE VALUE OF COLPOSCOPY EXAMINATION IN DIAGNOSIS OF PRECANCEROUS AND CANCEROUS DISEASES OF THE CERVIX].

The aim of this study is to present the value of colposcopy examination in diagnosis of precancerous and cancerous diseases of the cenvix. A retrospective study analyze 127 patients at SA GBAL" Dr. Shterev Hospital" that undenNent, firstly cervical smear test and secondly a colposcopic punch biopsy The patients are divided in two groups--one group of cytologically non-signaled patients with results from the Pap test I-II and one group with cytologically -signaled patients with results from the Pap test III-IV The data shows a correlation between the cytological and histological results of the second group and absence of such a correlation in the first group. In the non-signaled group the mild precancerous lesions to Thvasive cen'ical cancer were left undiagnosed. The conduct of a routine colposcopy during preventive gynecological examination will reduce the deficiencies of the cytological method and by amplifying it, it will lead to better results of the diagnosis and treatment of the precanceroses and the cervical cancer.

[MODELS OF CLINICAL IMPLEMENTATION OF CELL FREE FETAL DNA IN THE MATERNAL SERUM SCREENING TEST-ANALYSIS].

UNLABELLED: Prenatal screening by definition is a way of identifying pregnancies, with a high enough risk to specific fetal damage as to justify the subsequent invasive diagnosis among the seemingly normal pregnancies. [1] The aim of the prenatal screening test is to reach the high diagnostic frequency (DR > 95%), with low false-positive rate (FPR < 1%). Several non-invasive prenatal tests (NIPT) are widely adopted and use in clinical practice: 1st Trimester Combined screening (First trimester Combined Screening) and 2nd trimester biochemical screening (Second trimester biochemical screening) and in the last few years through screening Fetal DNA in Maternal serum (cfDNA screening). Since the introduction of the sfDNA test were examined and discussed the results of several ways of application: (1) as a primary screening method without preceding the result of 1st trimester combined screening for chromosomal abnormalities, (2) as a contingent test after 1st trimester combined screening in high risk pregnancies (> 1:100) (3) as a contingent test after 1st trimester combined screening, when the calculated risk is between ( 1:10 to 1:2500). The purpose of the study: to compare the results of different ways of application screening through cfDNA: detection rate (DR) for Tri21, Tri18 and Tri13, procentage of invasive diagnostics and cost-effectiveness ratio of cfDNA test in comparison with the 1st trimester combined screening. To establish the most suitable algorithm for application of cfDNA test. METHODS AND MATERIALS: Analyzed were the results of several randomized multi-center clinical studies whose data are processed through a meta-analysis. RESULTS: cfDNA-test has a higher DR for Tri21 for lower FPR, compared to the combined screening in 1st trimester (cfDNA-DR 99%, 1st trimester screening-DR 96% and 0.4%FPR, respectively FPR 5%), but although it is with better results and reduces the incidence of invasive tests, does not justify the significant difference in price-performance ratio. On the other hand cfDNA-test is with a lower detection rate for Tri 18 or 13 (93-95%), which makes it worse for a primary screening test instead of combined screening in the 1st trimester. CONCLUSIONS: The performance of cfDNA-test in terms of the three most common Trisomies: 21,18 and 13 is highest when used after (contingent to) 1st trimester screening and only for patients with an intermediate risk from 1-st trimester screening (risk > 1:10 and 1:2500, around 27% of all pregnancies), as it increases the diagnostic rate of combined screening for Down syndrome (from 90% to 98%), and significantly reduces the percentage of invasive diagnostics (from 3% to 0.7-1%) and that way we are able to achieve optimal result in price-performance result.