Publications by authors named "E Litwinska"

18 Publications

Stratification of pregnancy care based on risk of pre-eclampsia derived from biophysical and biochemical markers at 19-24 weeks' gestation.

Ultrasound Obstet Gynecol 2021 Apr 1. Epub 2021 Apr 1.

Harris Birthright Research Centre for Fetal Medicine, King's College, London, UK.

Objective: We have previously proposed that all pregnant women should have assessment of risk for preeclampsia (PE) at 20 and 36 weeks' gestation and that the 20 weeks assessment should be used to define subgroups requiring additional monitoring and reassessment at 28 and 32 weeks. The objective of this study is to examine the potential improvement in screening for PE with delivery at <28, <32, <36 and ≥36 weeks' gestation at 19-24 weeks' gestation by the addition of serum placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFLT-1) to the combination of maternal demographic characteristics and medical history, uterine artery pulsatility index (UtA-PI) and mean arterial pressure (MAP).

Methods: This was a prospective, non-intervention study in women attending for an ultrasound scan at 19-24 weeks as part of routine pregnancy care. Patient-specific risks of delivery with PE at <36 weeks' gestation were calculated using the competing risks model to combine the prior distribution of the gestational age at delivery with PE, obtained from maternal characteristics and medical history, with multiple of the median (MoM) values of UtA-PI, MAP, PlGF and sFLT-1. Different risk cut-offs were used to vary the proportion of the population stratified into each of four risk categories (very high-risk, high-risk, intermediate-risk and low-risk) with the intention of detecting about 80%, 85%, 90% and 95% of the cases of delivery with PE at <28, <32 and <36 weeks' gestation. The performance of screening was assessed by plotting the detection rate against the screen positive rate and calculating the areas under these curves and by proportion stratified to a given group for fixed detection rates. Model based estimates of screening performance for these various combinations of markers were also produced.

Results: In the study population of 37886 singleton pregnancies there were 1130 (3.0%) that subsequently developed PE, including 160 (0.4%) that delivered at <36 weeks' gestation. In both the modelled and empirical results there was incremental improvement in the performance of screening with the addition of PlGF and sFLT-1 to the combination of maternal factors, UtA-PI and MAP. If the objective of screening was to identify about 90% of cases of PE with delivery at <28, <32 and <36 weeks and the method of screening was a combination of maternal factors, UtA-PI and MAP, the respective screen positive rates would be 3.1%, 8.5%, and 19.1%. The respective values for screening by maternal factors, UtA-PI, MAP and PlGF were 0.2%, 0.7% and 10.6% and for screening by maternal factors, UtA-PI, MAP, PlGF and sFLT-1 were 0.1%, 0.4% and 9.5%. The empirical results were consistent with the modelled ones. There was good agreement between the predicted risk and observed incidence of PE <36 weeks' gestation with all three strategies of screening.

Conclusion: The performance of screening for PE with delivery at <28, <32 and <36 weeks' gestation at 19-24 weeks' gestation achieved by a combination of maternal demographic characteristics and medical history, UtA-PI and MAP is improved by the addition of serum PlGF and sFLT-1. The performance of screening for PE at ≥36 weeks' gestation is poor irrespective of the method of screening at 19-24 weeks. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/uog.23640DOI Listing
April 2021

Stratification of pregnancy care based on risk of pre-eclampsia derived from uterine artery Doppler at 19-24 weeks' gestation.

Ultrasound Obstet Gynecol 2021 Mar 1. Epub 2021 Mar 1.

Harris Birthright Research Centre for Fetal Medicine, King's College Hospital, London, UK.

Objectives: There were two objectives of this study. First, to examine the value of uterine artery pulsatility index (UtA-PI) at 19-24 weeks' gestation in the prediction of subsequent development of pre-eclampsia (PE) and to compare the performance of screening between the use of, first, fixed cut-offs of UtA-PI, second, percentile cut-offs of UtA-PI adjusted for gestational age, third, a competing-risks model combining maternal demographic characteristics and medical history with UtA-PI, and, fourth, a competing-risks model combining maternal factors with UtA-PI and mean arterial pressure (MAP). Second, to stratify pregnancy care based on the estimated risk of PE at 19-24 weeks' gestation from UtA-PI and combinations of maternal factors with UtA-PI and MAP.

Methods: This was a prospective, non-intervention study in women attending for an ultrasound scan at 19-24 weeks as part of routine pregnancy care. Patient-specific risks of delivery with PE at < 36 weeks' gestation were calculated using the competing-risks model to combine the prior distribution of the gestational age at delivery with PE, obtained from maternal characteristics and medical history, with multiples of the median (MoM) values of UtA-PI and MAP. Different risk cut-offs were used to vary the proportion of the population stratified into each risk category (very high risk, high risk, intermediate risk and low risk) with the intention of detecting about 80%, 85%, 90% and 95% of cases of delivery with PE at < 28, < 32 and < 36 weeks' gestation. We also examined the performance of screening by maternal factors and UtA-PI MoM, fixed cut-offs of UtA-PI and percentile cut-offs of UtA-PI adjusted for gestational age. Calibration for risks for PE < 36 weeks' gestation by the combination of maternal factors, UtA-PI MoM and MAP MoM was assessed by plotting the observed incidence of PE against the predicted incidence. Additionally, we developed reference ranges of transabdominal and transvaginal measurement of UtA-PI according to gestational age.

Results: In the study population of 96 678 singleton pregnancies, there were 2866 (3.0%) that subsequently developed PE, including 467 (0.5%) that delivered at < 36 weeks' gestation. If the objective of screening was to identify about 90% of cases of delivery with PE at < 28, < 32 and < 36 weeks and the method of screening was a combination of maternal factors, UtA-PI MoM and MAP MoM, the proportion of the population stratified into very high-risk, high-risk, intermediate-risk and low-risk groups would be 2.4%, 3.9%, 17.8% and 75.9%, respectively; the respective values were 6.0%, 3.0%, 21.0% and 70.0% if screening was by maternal factors and UtA-PI MoM, 5.7%, 7.5%, 49.8% and 37.0% if screening was by fixed cut-offs of UtA-PI and 6.9%, 5.2%, 49.0% and 38.9% if screening was by percentile cut-offs of UtA-PI. In the validation of the prediction model based on a combination of maternal factors and MoM values of UtA-PI and MAP, calibration plots demonstrated good agreement between the predicted risk and the observed incidence of PE.

Conclusions: All pregnant women should have screening for PE at 20 and 36 weeks' gestation. The findings at 20 weeks can be used to identify the subgroups that require additional monitoring and reassessment at 28 and 32 weeks. The performance of screening by a combination of maternal factors and MoM values of UtA-PI and MAP at 19-24 weeks for delivery with PE at < 28, < 32 and < 36 weeks' gestation is superior to that of screening by a combination of maternal factors and UtA-PI MoM, by fixed cut-offs of UtA-PI or by percentile cut-offs of UtA-PI. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.
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http://dx.doi.org/10.1002/uog.23623DOI Listing
March 2021

Fetal endoscopic tracheal occlusion reverses the natural history of right-sided congenital diaphragmatic hernia: European multicenter experience.

Ultrasound Obstet Gynecol 2021 Mar;57(3):378-385

Clinical Department of Obstetrics and Gynaecology, Fetal Medicine Unit, University Hospitals Leuven, Leuven, Belgium.

Objective: To evaluate the neonatal outcome of fetuses with isolated right-sided congenital diaphragmatic hernia (iRCDH) based on prenatal severity indicators and antenatal management.

Methods: This was a retrospective review of prospectively collected data on consecutive cases diagnosed with iRCDH before 30 weeks' gestation in four fetal therapy centers, between January 2008 and December 2018. Data on prenatal severity assessment, antenatal management and perinatal outcome were retrieved. Univariate and multivariate logistic regression analysis were used to identify predictors of survival at discharge and early neonatal morbidity.

Results: Of 265 patients assessed during the study period, we excluded 40 (15%) who underwent termination of pregnancy, two cases of unexplained fetal death, two that were lost to follow-up, one for which antenatal assessment of lung hypoplasia was not available and six cases which were found to have major associated anomalies or syndromes after birth. Of the 214 fetuses with iRCDH included in the neonatal outcome analysis, 86 were managed expectantly during pregnancy and 128 underwent fetal endoscopic tracheal occlusion (FETO) with a balloon. In the expectant-management group, lung size measured by ultrasound or by magnetic resonance imaging was the only independent predictor of survival (observed-to-expected lung-to-head ratio (o/e-LHR) odds ratio (OR), 1.06 (95% CI, 1.02-1.11); P = 0.003). Until now, stratification for severe lung hypoplasia has been based on an o/e-LHR cut-off of 45%. In cases managed expectantly, the survival rate was 15% (4/27) in those with o/e-LHR ≤ 45% and 61% (36/59) for o/e-LHR > 45% (P = 0.001). However, the best o/e-LHR cut-off for the prediction of survival at discharge was 50%, with a sensitivity of 78% and specificity of 72%. In the expectantly managed group, survivors with severe pulmonary hypoplasia stayed longer in the neonatal intensive care unit than did those with mildly hypoplastic lungs. In fetuses with an o/e-LHR ≤ 45% treated with FETO, survival rate was higher than in those with similar lung size managed expectantly (49/120 (41%) vs 4/27 (15%); P = 0.014), despite higher prematurity rates (gestational age at birth: 34.4 ± 2.7 weeks vs 36.8 ± 3.0 weeks; P < 0.0001). In fetuses treated with FETO, gestational age at birth was the only predictor of survival (OR, 1.25 (95% CI, 1.04-1.50); P = 0.02).

Conclusions: Antenatal measurement of lung size can predict survival in iRCDH. In fetuses with severe lung hypoplasia, FETO was associated with a significant increase in survival without an associated increase in neonatal morbidity. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.
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http://dx.doi.org/10.1002/uog.23115DOI Listing
March 2021

Diagnosis of fetal defects in twin pregnancies at routine 11-13-week ultrasound examination.

Ultrasound Obstet Gynecol 2020 Apr 6;55(4):474-481. Epub 2020 Mar 6.

Fetal Medicine Research Institute, King's College Hospital, London, UK.

Objectives: To examine the performance of the routine 11-13-week scan in detecting fetal defects in twin pregnancies and to examine if, in pregnancies with a fetal defect, compared to those with normal fetuses, there is increased incidence of nuchal translucency thickness (NT) ≥ 95 and ≥ 99 percentiles or intertwin discordance in crown-rump length (CRL) ≥ 10% and ≥ 15%.

Methods: This was a retrospective analysis of prospectively collected data in twin pregnancies undergoing routine ultrasound examination for fetal anatomy, according to standardized protocols, at 11-13 weeks' gestation between 2002 and 2019. Pregnancies with known chromosomal abnormality were excluded. The final diagnosis of fetal defect was based on the results of postnatal examination in cases of live birth and on the findings of the last ultrasound examination in cases of pregnancy termination, miscarriage or stillbirth. The performance of the 11-13-week scan in the detection of fetal defects was determined.

Results: The study population of 6366 twin pregnancies with two live fetuses at 11-13 weeks' gestation included 4979 (78.2%) dichorionic (DC) and 1387 (21.8%) monochorionic (MC) twin pregnancies. The main findings were: first, the overall incidence of fetal defects was higher in MC than in DC twins (2.8% vs 1.3%); second, the proportion of defects diagnosed in the first trimester was higher in MC than in DC twins (52.6% vs 27.1%); third, the pattern of defects in relation to detectability at the 11-13-week scan (always detectable, sometimes detectable and never detectable) was similar to that reported previously in singleton pregnancies; fourth, always-detectable defects included acrania, alobar holoprosencephaly, encephalocele, pentalogy of Cantrell, exomphalos, body-stalk anomaly, twin reversed arterial perfusion sequence and conjoined twins; fifth, the incidence of fetal NT ≥ 95 percentile was higher in those with than in those without a defect (16.5% vs 4.5% in DC twins and 19.2% vs 5.9% in MC twins) and this was also true for NT ≥ 99 percentile (8.3% vs 1.0% in DC twins and 15.4% vs 2.0% in MC twins); and sixth, the incidence of CRL discordance ≥ 10% was higher in those with than in those without a defect (20.2% vs 7.9% in DC twins and 33.8% vs 9.3% in MC twins) and this was also true for CRL discordance ≥ 15% (10.1% vs 1.9% in DC twins and 28.2% vs 2.8% in MC twins).

Conclusions: First, fetal defects are more common in MC than in DC twin pregnancies. Second, first-trimester detection of fetal defects in DC twin pregnancies is similar to that in singleton pregnancies. Third, first-trimester detectability of defects in MC twins is higher than in DC twins. Fourth, in twin pregnancies with a fetal defect, there is higher intertwin discordance in CRL and incidence of increased NT, but the predictive performance of screening by these markers is poor. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.
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http://dx.doi.org/10.1002/uog.21938DOI Listing
April 2020

Increased nuchal translucency at 11-13 weeks' gestation and outcome in twin pregnancy.

Ultrasound Obstet Gynecol 2020 Mar 13;55(3):318-325. Epub 2020 Feb 13.

Harris Birthright Research Centre for Fetal Medicine, King's College Hospital, London, UK.

Objective: To investigate the value of increased fetal nuchal translucency thickness (NT) at the 11-13-week scan in the prediction of adverse outcome in dichorionic (DC), monochorionic diamniotic (MCDA) and monochorionic monoamniotic (MCMA) twin pregnancies.

Methods: This was a retrospective analysis of prospectively collected data on twin pregnancies undergoing routine ultrasound examination at 11-13 weeks' gestation between 2002 and 2019. In pregnancies with no major defects or chromosomal abnormalities, we examined the value of increased NT ≥ 95 percentile in one or both fetuses in the prediction of, first, miscarriage or death of one or both fetuses at < 20 and < 24 weeks' gestation in DC, MCDA and MCMA twin pregnancies, second, death of one or both fetuses or neonates at ≥ 24 weeks in DC, MCDA and MCMA twin pregnancies, third, development of twin-twin transfusion syndrome (TTTS) or selective fetal growth restriction (sFGR) treated by endoscopic laser surgery at < 20 and ≥ 20 weeks' gestation in MCDA pregnancies, and, fourth, either fetal loss or laser surgery at < 20 weeks' gestation in MCDA pregnancies.

Results: The study population of 6225 twin pregnancies included 4896 (78.7%) DC, 1274 (20.5%) MCDA and 55 (0.9%) MCMA pregnancies. The incidence of NT ≥ 95 percentile in one or both fetuses in DC twin pregnancies was 8.3%; in MCDA twins the incidence was significantly higher (10.4%; P = 0.016), but in MCMA twins it was not significantly different (9.1%; P = 0.804) from that in DC twins. In DC twin pregnancies, the incidence of high NT was not significantly different between those with two survivors and those with adverse outcome. In MCMA twin pregnancies, the number of cases was too small for meaningful assessment of the relationship between high NT and adverse outcome. In MCDA twin pregnancies with at least one fetal death or need for endoscopic laser surgery at < 20 weeks' gestation, the incidence of NT ≥ 95 percentile was significantly higher than in those with two survivors (23.5% vs 9.8%; P < 0.0001). Kaplan-Meier analysis in MCDA twin pregnancies showed that, in those with NT ≥ 95 percentile, there was significantly lower survival at < 20 weeks' gestation than in those with NT < 95 percentile (P = 0.001); this was not the case for survival at ≥ 20 weeks (P = 0.960). The performance of screening by fetal NT ≥ 95 percentile for prediction of either fetal loss or need for endoscopic laser surgery at < 20 weeks' gestation was poor, with a detection rate of 23.5% at a false-positive rate of 8.9%, and the relative risk, in comparison to fetal NT < 95 percentile, was 2.640 (95% CI, 1.854-3.758; P < 0.0001). In MCDA twin pregnancies, the overall rate of fetal loss or need for laser surgery at < 20 weeks' gestation was 10.7% but, in the subgroups with NT ≥ 95 and NT ≥ 99 percentiles, which constituted 10.4% and 3.3% of the total, the rates increased to 24.1% and 40.5%, respectively.

Conclusions: In MCDA twin pregnancies with no major fetal abnormalities, measurement of NT at the 11-13-week scan is a poor screening test for adverse pregnancy outcome. However, the finding in one or both fetuses of NT ≥ 95 percentile, and more so ≥ 99 percentile, is associated with a substantially increased risk of fetal loss or need for endoscopic laser surgery at < 20 weeks' gestation. The extent to which closer monitoring and earlier intervention in the high-risk group can reduce these complications remains to be determined. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.
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http://dx.doi.org/10.1002/uog.21935DOI Listing
March 2020