Publications by authors named "Basky Thilaganathan"

103 Publications

The placenta and preeclampsia: villain or victim?

Am J Obstet Gynecol 2021 Mar 24. Epub 2021 Mar 24.

Molecular and Clinical Sciences Research Institute, St George's University of London, London, United Kingdom; Fetal Medicine Unit, Department of Obstetrics and Gynaecology, St George's University Hospitals NHS Foundation Trust, London, United Kingdom. Electronic address:

Preeclampsia is a disease whose characterization has not changed in the 150 years since the cluster of signs associated with the disorder were first described. Although our understanding of the pathophysiology of preeclampsia has advanced considerably since then, there is still little consensus regarding the true etiology of preeclampsia. As a consequence, preeclampsia has earned the moniker "disease of theories," predominantly because the underlying biological mechanisms linking clinical epidemiologic findings to observed organ dysfunction in preeclampsia are far from clear. Despite the lack of cohesive evidence, expert consensus favors the hypothesis that preeclampsia is a primary placental disorder. However, there is now emerging evidence that suboptimal maternal cardiovascular performance resulting in uteroplacental hypoperfusion is more likely to be the cause of secondary placental dysfunction in preeclampsia. Preeclampsia and cardiovascular disease share the same risk factors, preexisting cardiovascular disease is the strongest risk factor (chronic hypertension, congenital heart disease) for developing preeclampsia, and there are now abundant data from maternal echocardiography and angiogenic marker studies that cardiovascular dysfunction precedes the development of preeclampsia by several weeks or months. Importantly, cardiovascular signs and symptoms (hypertension, cerebral edema, cardiac dysfunction) predominate in preeclampsia at clinical presentation and persist into the postnatal period with a 30% risk of chronic hypertension in the decade after birth. Placental malperfusion caused by suboptimal maternal cardiovascular performance may lead to preeclampsia, thereby explaining the preponderance of cardiovascular drugs (aspirin, calcium, statins, metformin, and antihypertensives) in preeclampsia prevention strategies. Despite the seriousness of the maternal and fetal consequences, we are still developing sensitive screening, reliable diagnostic, effective therapeutic, or improvement strategies for postpartum maternal cardiovascular legacy in preeclampsia. The latter will only become clear with an acceptance and understanding of the cardiovascular etiology of preeclampsia.
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http://dx.doi.org/10.1016/j.ajog.2020.10.024DOI Listing
March 2021

Validation and development of models using clinical, biochemical and ultrasound markers for predicting pre-eclampsia: an individual participant data meta-analysis.

Health Technol Assess 2020 12;24(72):1-252

Background: Pre-eclampsia is a leading cause of maternal and perinatal mortality and morbidity. Early identification of women at risk is needed to plan management.

Objectives: To assess the performance of existing pre-eclampsia prediction models and to develop and validate models for pre-eclampsia using individual participant data meta-analysis. We also estimated the prognostic value of individual markers.

Design: This was an individual participant data meta-analysis of cohort studies.

Setting: Source data from secondary and tertiary care.

Predictors: We identified predictors from systematic reviews, and prioritised for importance in an international survey.

Primary Outcomes: Early-onset (delivery at < 34 weeks' gestation), late-onset (delivery at ≥ 34 weeks' gestation) and any-onset pre-eclampsia.

Analysis: We externally validated existing prediction models in UK cohorts and reported their performance in terms of discrimination and calibration. We developed and validated 12 new models based on clinical characteristics, clinical characteristics and biochemical markers, and clinical characteristics and ultrasound markers in the first and second trimesters. We summarised the data set-specific performance of each model using a random-effects meta-analysis. Discrimination was considered promising for -statistics of ≥ 0.7, and calibration was considered good if the slope was near 1 and calibration-in-the-large was near 0. Heterogeneity was quantified using and τ. A decision curve analysis was undertaken to determine the clinical utility (net benefit) of the models. We reported the unadjusted prognostic value of individual predictors for pre-eclampsia as odds ratios with 95% confidence and prediction intervals.

Results: The International Prediction of Pregnancy Complications network comprised 78 studies (3,570,993 singleton pregnancies) identified from systematic reviews of tests to predict pre-eclampsia. Twenty-four of the 131 published prediction models could be validated in 11 UK cohorts. Summary -statistics were between 0.6 and 0.7 for most models, and calibration was generally poor owing to large between-study heterogeneity, suggesting model overfitting. The clinical utility of the models varied between showing net harm to showing minimal or no net benefit. The average discrimination for IPPIC models ranged between 0.68 and 0.83. This was highest for the second-trimester clinical characteristics and biochemical markers model to predict early-onset pre-eclampsia, and lowest for the first-trimester clinical characteristics models to predict any pre-eclampsia. Calibration performance was heterogeneous across studies. Net benefit was observed for International Prediction of Pregnancy Complications first and second-trimester clinical characteristics and clinical characteristics and biochemical markers models predicting any pre-eclampsia, when validated in singleton nulliparous women managed in the UK NHS. History of hypertension, parity, smoking, mode of conception, placental growth factor and uterine artery pulsatility index had the strongest unadjusted associations with pre-eclampsia.

Limitations: Variations in study population characteristics, type of predictors reported, too few events in some validation cohorts and the type of measurements contributed to heterogeneity in performance of the International Prediction of Pregnancy Complications models. Some published models were not validated because model predictors were unavailable in the individual participant data.

Conclusion: For models that could be validated, predictive performance was generally poor across data sets. Although the International Prediction of Pregnancy Complications models show good predictive performance on average, and in the singleton nulliparous population, heterogeneity in calibration performance is likely across settings.

Future Work: Recalibration of model parameters within populations may improve calibration performance. Additional strong predictors need to be identified to improve model performance and consistency. Validation, including examination of calibration heterogeneity, is required for the models we could not validate.

Study Registration: This study is registered as PROSPERO CRD42015029349.

Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in ; Vol. 24, No. 72. See the NIHR Journals Library website for further project information.
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http://dx.doi.org/10.3310/hta24720DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7780127PMC
December 2020

External validation of prognostic models predicting pre-eclampsia: individual participant data meta-analysis.

BMC Med 2020 11 2;18(1):302. Epub 2020 Nov 2.

Institute of Metabolism and Systems Research, WHO Collaborating Centre for Women's Health, University of Birmingham, Birmingham, UK.

Background: Pre-eclampsia is a leading cause of maternal and perinatal mortality and morbidity. Early identification of women at risk during pregnancy is required to plan management. Although there are many published prediction models for pre-eclampsia, few have been validated in external data. Our objective was to externally validate published prediction models for pre-eclampsia using individual participant data (IPD) from UK studies, to evaluate whether any of the models can accurately predict the condition when used within the UK healthcare setting.

Methods: IPD from 11 UK cohort studies (217,415 pregnant women) within the International Prediction of Pregnancy Complications (IPPIC) pre-eclampsia network contributed to external validation of published prediction models, identified by systematic review. Cohorts that measured all predictor variables in at least one of the identified models and reported pre-eclampsia as an outcome were included for validation. We reported the model predictive performance as discrimination (C-statistic), calibration (calibration plots, calibration slope, calibration-in-the-large), and net benefit. Performance measures were estimated separately in each available study and then, where possible, combined across studies in a random-effects meta-analysis.

Results: Of 131 published models, 67 provided the full model equation and 24 could be validated in 11 UK cohorts. Most of the models showed modest discrimination with summary C-statistics between 0.6 and 0.7. The calibration of the predicted compared to observed risk was generally poor for most models with observed calibration slopes less than 1, indicating that predictions were generally too extreme, although confidence intervals were wide. There was large between-study heterogeneity in each model's calibration-in-the-large, suggesting poor calibration of the predicted overall risk across populations. In a subset of models, the net benefit of using the models to inform clinical decisions appeared small and limited to probability thresholds between 5 and 7%.

Conclusions: The evaluated models had modest predictive performance, with key limitations such as poor calibration (likely due to overfitting in the original development datasets), substantial heterogeneity, and small net benefit across settings. The evidence to support the use of these prediction models for pre-eclampsia in clinical decision-making is limited. Any models that we could not validate should be examined in terms of their predictive performance, net benefit, and heterogeneity across multiple UK settings before consideration for use in practice.

Trial Registration: PROSPERO ID: CRD42015029349 .
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http://dx.doi.org/10.1186/s12916-020-01766-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7604970PMC
November 2020

Authors' reply re: Implementation of routine first-trimester combined screening for pre-eclampsia: a clinical effectiveness study.

BJOG 2021 01 3;128(1):141. Epub 2020 Sep 3.

Fetal Medicine Unit, St George's University Hospitals NHS Foundation Trust, London, UK.

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http://dx.doi.org/10.1111/1471-0528.16444DOI Listing
January 2021

Performance of Antenatal Diagnostic Criteria of Twin-Anemia-Polycythemia Sequence.

J Clin Med 2020 Aug 26;9(9). Epub 2020 Aug 26.

Fetal Medicine Unit, St George's University Hospitals, Blackshaw Road, London SW17 0QT, UK.

This study aims to elicit the validation performance of different diagnostic criteria and to evaluate the disease course and perinatal outcomes of pregnancies complicated by twin anemia polycythemia sequence (TAPS). Monochorionic diamniotic (MCDA) twin pregnancies who received serial middle cerebral artery (MCA) peak systolic velocity (PSV) measurements without non-TAPS-related demise or major anomalies were included. Course of disease, antenatal intervention, additional ultrasound features, and perinatal outcomes were compared between each criteria and onset. Forty-nine cases of TAPS and 203 non-TAPS controls were identified. The incidence of TAPS was 19.2%, 15.7%, 7.8%, and 6.3% for ΔPSV MoM > 0.373, ΔPSV MoM > 0.5, traditional, and Delphi consensus criteria, respectively ( < 0.001). The incidence of antenatal intervention was 55.1, 62.5, 75.0, and 87.5%, respectively. Furthermore, cases detected according to the Delphi consensus criteria had a higher rate of progression or intervention compared to cases detected with ΔPSV MoM > 0.373 (87.0 vs. 59.0%, = 0.037). TAPS had a significantly higher birth weight discordance than uncomplicated MCDA twins (25.3 vs. 7.3%, < 0.001). Application of four different diagnostic criteria for TAPS leads to significant differences in the incidence, severity, and antenatal intervention. The Delphi criteria identified more severe cases likely to require intervention, and the delta PSV > 0.373 criteria identified milder cases, without a significant impact on neonatal outcomes.
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http://dx.doi.org/10.3390/jcm9092754DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563169PMC
August 2020

Diagnostic accuracy of fetal choroid plexus length to head biometry ratio at 11 to 13 weeks for open spina bifida.

Am J Obstet Gynecol 2021 03 22;224(3):294.e1-294.e14. Epub 2020 Aug 22.

Fetal Medicine Unit, St George's Hospital, St George's University of London, London, United Kingdom; Vascular Biology Research Centre, Molecular and Clinical Sciences Research Institute, St George's University of London, London, United Kingdom. Electronic address:

Background: Open spina bifida is a major congenital anomaly with an estimated incidence of <1 in 1000. The diagnosis of open spina bifida is usually made during the second trimester, but first-trimester detection rate of spina bifida is increasingly reported. Recently, the mean choroid plexus length to occipitofrontal diameter ratio was reported to be increased in fetuses with open spina bifida. The ratio reflects the so-called dry brain effect caused by cerebrospinal fluid leakage and expansion of the choroid plexus into the lateral ventricles. The mean choroid plexus length to occipitofrontal diameter ratio appears to be a promising tool for early detection of open spina bifida, but its diagnostic accuracy is yet to be determined in a large cohort.

Objective: This study aimed to assess the predictive accuracy of mean choroid plexus length to occipitofrontal diameter ratio recorded at 11 to 13 weeks' gestation for the detection of open spina bifida.

Study Design: This was a retrospective cohort of patients treated in a tertiary referral center. Fetuses in which open spina bifida was detected at 16 to 24 weeks' gestation and normal fetuses were included in the cohort. Biparietal diameter and occipitofrontal diameter were measured in an axial view. The length of choroid plexus was measured along its longest diameter in the same plane. Ultrasound images were examined offline, and the operator was blinded to the clinical diagnosis. The predictive accuracy was evaluated using the area under the curve and positive and negative predictive values.

Results: We included 3300 pregnant women, of whom 24 (0.73%) had the fetuses affected by open spina bifida. The area under the curve values were 0.921 for mean choroid plexus length to occipitofrontal diameter ratio and 0.933 for its multiple of the median. Mean choroid plexus length to biparietal diameter ratio indicated similar results, with area under the curve values of 0.928 and 0.931 for raw ratio and multiple of the median ratio models, respectively. The optimal cutoffs of the mean choroid plexus to occipitofrontal diameter ratio and multiple of the median ratios were 0.662 and 1.263, respectively. The optimal mean choroid plexus to occipitofrontal diameter ratio and multiple of the median ratio cutoffs provided a positive predictive value of 90.9% and a negative predictive value of 99.6%. The number of affected spinal segments was significantly higher in fetuses with a ratio above 0.662 (P=.022).

Conclusion: The mean choroid plexus length to occipitofrontal diameter ratio at 11 to 13 weeks' gestation is a promising tool for the prenatal detection of open spina bifida.
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http://dx.doi.org/10.1016/j.ajog.2020.08.058DOI Listing
March 2021

The Association Between Hypertension in Pregnancy and Preterm Birth with Fetal Growth Restriction in Singleton and Twin Pregnancy: Use of Twin Versus Singleton Charts.

J Clin Med 2020 Aug 5;9(8). Epub 2020 Aug 5.

Fetal Medicine Unit, St George's Hospital, St George's University of London, Cranmer Terrace, London SW17 0RE, UK.

Objective: To compare the rates of fetal growth restriction (FGR) in singleton and twin pregnancies using singleton and twin-specific birthweight standards.

Methods: The study included liveborn twin and singleton pregnancies between January 2000 and January 2019. Hypertensive disorders of pregnancy (HDP) included gestational hypertension and pre-eclampsia. The study outcomes were FGR or small-for-gestational-age (SGA) at birth as assessed using singleton and twin reference charts.

Results: The analysis included 1473 twin and 62,432 singleton pregnancies. In singleton pregnancies the risk of PTB <34 weeks without HDP (OR 2.82, < 0.001), delivery ≥34 weeks with HDP (OR 2.38, < 0.001), and PTB <34 weeks with HDP (OR 13.65, < 0.001) were significantly higher in the pregnancies complicated by FGR compared to those without. When selective fetal growth restriction (sFGR) was assessed using the singleton standard, the risk of PTB <34 weeks without HDP (OR 1.03, = 0.872), delivery ≥34 weeks with HDP (OR 1.36, = 0.160) were similar in the pregnancies complicated by sFGR compared to those without, while the risk of PTB <34 weeks with HDP (OR 2.41, = 0.025) was significantly higher in the pregnancies complicated by sFGR compared to those without. When sFGR was assessed using the twin-specific chart, the risk of PTB <34 weeks without HDP (OR 3.55, < 0.001), delivery ≥34 weeks with HDP (OR 3.17, = 0.004), and PTB <34 weeks with HDP (OR 5.69, < 0.001) were significantly higher in the pregnancies complicated by sFGR compared to those without. The stronger and more consistent association persisted in the subgroup analyses according to chorionicity. The strength of association in dichorionic twin pregnancies resembles that of the singletons more closely and consistently when the FGR was diagnosed using the twin-specific charts.

Conclusion: FGR in twin pregnancies has a stronger and more consistent association with HDP and PTB when using twin-specific rather than singleton charts. This study provides further evidence supporting the use of twin-specific charts when assessing fetal growth in twin pregnancies.
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http://dx.doi.org/10.3390/jcm9082518DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7464003PMC
August 2020

Maternal Cardiac Dysfunction Precedes Development of Preeclampsia.

Hypertension 2020 08 8;76(2):321-322. Epub 2020 Jul 8.

From the Vascular Biology Research Centre, Molecular and Clinical Sciences Research Institute, St George's University of London, United Kingdom; Fetal Medicine Unit, Department of Obstetrics and Gynaecology, St George's University Hospitals NHS Foundation Trust, London, United Kingdom; and Tommy's National Centre for Maternity Improvement, Royal College of Obstetrics and Gynaecology, London.

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http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.15281DOI Listing
August 2020

Prognostic Value of Maternal Cardiovascular Hemodynamics in Women With Gestational Hypertension and Chronic Hypertension in Pregnancy.

Hypertension 2020 08 15;76(2):506-513. Epub 2020 Jun 15.

From the Fetal Medicine Unit, St George's Hospital (E.K., H.P., B.T., A.K.), St George's University of London, United Kingdom.

This study aimed to assess the prognostic value of cardiovascular assessment in women with gestational hypertension or chronic hypertension for the risk of preeclampsia and need for closer antenatal surveillance. This was a prospective study of pregnancies complicated by gestational hypertension or chronic hypertension presenting to St George's Hospital, between January 2015 and May 2018. A noninvasive ultrasonic cardiac output monitor was used to obtain cardiovascular variables of cardiac output (CO) and systemic vascular resistance (SVR) and weight-adjusted indices. The primary outcome was the time to development of preeclampsia in women with gestational hypertension or chronic hypertension. In women with gestational hypertension or chronic hypertension (n=149), cox-proportional hazards analysis showed that mean arterial pressure (=0.006), Afro-Caribbean ethnicity (=0.045), and gestational age at the time of diagnosis above 34 weeks (<0.001) were significantly associated with increased risk of earlier preeclampsia. Women with high SVR and normal CO (adjusted hazard ratio, 2.32 [95% CI, 1.06-5.08]; =0.035) and high SVR and low CO (adjusted hazard ratio, 7.79 [95% CI, 1.94-31.24]; =0.003) cardiovascular profiles had significantly higher risk of earlier preeclampsia compared with women with normal SVR and normal CO. The findings of this study demonstrate that hypertensive women with increased SVR and low CO had a higher risk of developing preeclampsia sooner.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.14982DOI Listing
August 2020

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

J Clin Med 2020 Jun 5;9(6). Epub 2020 Jun 5.

Department of Obstetrics, Division of Fetal therapy, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.

The aim of this study was to investigate the management and outcome in the post-laser twin anemia polycythemia sequence (TAPS). Data of the international TAPS Registry, collected between 2014 and 2019, were used for this study. The primary outcomes were perinatal mortality and severe neonatal morbidity. Secondary outcomes included a risk factor analysis for perinatal mortality and severe neonatal morbidity. A total of 164 post-laser TAPS pregnancies were included, of which 92% (151/164) were diagnosed antenatally and 8% (13/164) postnatally. The median number of days between laser for TTTS and detection of TAPS was 14 (IQR: 7-28, range: 1-119). Antenatal management included expectant management in 43% (62/151), intrauterine transfusion with or without partial exchange transfusion in 29% (44/151), repeated laser surgery in 15% (24/151), selective feticide in 7% (11/151), delivery in 6% (9/151), and termination of pregnancy in 1% (1/151). The median gestational age (GA) at birth was 31.7 weeks (IQR: 28.6-33.7; range: 19.0-41.3). The perinatal mortality rate was 25% (83/327) for the total group, 37% (61/164) for donors, and 14% (22/163) for recipients ( < 0.001). Severe neonatal morbidity was detected in 40% (105/263) of the cohort and was similar for donors (43%; 51/118) and recipients (37%; 54/145), = 0.568. Independent risk factors for spontaneous perinatal mortality were antenatal TAPS Stage 4 (OR = 3.4, 95%CI 1.4-26.0, = 0.015), TAPS donor status (OR = 4.2, 95%CI 2.1-8.3, < 0.001), and GA at birth (OR = 0.8, 95%CI 0.7-0.9, = 0.001). Severe neonatal morbidity was significantly associated with GA at birth (OR = 1.5, 95%CI 1.3-1.7, < 0.001). In conclusion, post-laser TAPS most often occurs within one month after laser for TTTS, but may develop up to 17 weeks after initial surgery. Management is mostly expectant, but varies greatly, highlighting the lack of consensus on the optimal treatment and heterogeneity of the condition. Perinatal outcome is poor, particularly due to the high rate of perinatal mortality in donor twins.
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http://dx.doi.org/10.3390/jcm9061759DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7355738PMC
June 2020

Maternal and Perinatal Outcomes of White Coat Hypertension During Pregnancy: A Systematic Review and Meta-Analysis.

Hypertension 2020 07 26;76(1):157-166. Epub 2020 May 26.

Vascular Biology Research Centre, Molecular and Clinical Sciences Research Institute, St George's University of London, United Kingdom (B.T., A.K.).

The aim of this meta-analysis is to investigate whether white-coat hypertension (WCH) has an adverse effect on maternal, fetal, and neonatal outcomes. Medline, EMBASE, www.Clinicaltrials.gov, and Cochrane Library databases were searched electronically in December 2019. The outcomes were compared between pregnant women with WCH and normotensive controls, women with chronic hypertension, gestational hypertension or any hypertensive disorder of pregnancy. Twelve studies were eligible for inclusion in the systematic review. Women with WCH enrolled below 20 weeks had a significantly increased risk of preeclampsia (pooled risk ratio [RR], 5.43 [95% CI, 2.00-14.71]). Furthermore, women with WCH had increased risk of delivering a small-for-gestational-age newborn (RR, 2.47 [95% CI, 1.21-5.05], =0.013) and preterm birth (RR, 2.86 [95% CI, 1.44-5.68], =0.002). The risk of preeclampsia (risk ratio, 0.43 [95% CI, 0.23-0.78], =0.005), small-for-gestational-age (RR, 0.46 [95% CI, 0.26-0.82], =0.008), preterm birth (RR, 0.47 [95% CI, 0.31-0.71], <0.001) were significantly lower with WCH compared with women with gestational hypertension. Women with WCH delivered ≈1 week later compared with women with chronic hypertension (mean difference, 1.06 weeks [95% CI, 0.44-1.67 weeks]; <0.001). WCH is associated with a worse perinatal and maternal outcome than normotension, but better outcomes than gestational hypertension and chronic hypertension. Therefore, diagnosis of WCH should be ascertained in pregnant women presenting with hypertension. When the diagnosis is confirmed, these women require monitoring for developing preeclampsia, small-for-gestational-age and preterm birth.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.119.14627DOI Listing
July 2020

The Prognostic Value of Angiogenic Markers in Twin Pregnancies to Predict Delivery Due to Maternal Complications of Preeclampsia.

Hypertension 2020 07 26;76(1):176-183. Epub 2020 May 26.

Department of Obstetrics and Gynecology, Ankara University, Turkey (E.K.).

The sFlt-1 (soluble fms-like tyrosine kinase-1), PlGF (placental growth factor), and their ratio are useful for predicting delivery because of preeclampsia in singleton pregnancies. Evidence on the utility of sFlt-1/PlGF ratio in twin pregnancies is lacking. We aimed to evaluate the predictive value of sFlt-1/PlGF ratio for delivery because of preeclampsia in twins. A retrospective data analysis of 164 twin pregnancies with suspected preeclampsia was performed. The sFlt-1/PlGF ratio, which was known to clinicians, was significantly higher in women who delivered within 1 and 2 weeks compared with those who did not (median: 98.9 and 84.2 versus 23.5 pg/mL, respectively; <0.001). The area under the curve values sFlt-1/PlGF ratio levels were 0.88 (95% CI, 0.83-0.84) and 0.88 (95% CI, 0.83-0.93) for predicting delivery because of preeclampsia within 1 and 2 weeks of blood sampling, respectively. The predictive accuracy of sFlt-1/PlGF was independent of gestational age at sampling and chorionicity (>0.100 for interaction). The area under the curve values of sFlt-1/PlGF were significantly higher than for PlGF alone (mean 0.88 and 0.88 versus 0.81 and 0.80) for predicting delivery because of preeclampsia within 1 and 2 weeks of blood sampling (=0.055 and 0.001, respectively). sFlt-1/PlGF ratio lower than 38 was able to rule-out delivery within 1 and 2 weeks with a negative predictive value of 98.8% and 96.4% for delivery because of preeclampsia within 1 and 2 weeks, respectively. A cutoff of 38 is applicable for ruling out delivery because of preeclampsia in twin pregnancies.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.14957DOI Listing
July 2020

Stillbirth at term: Does size really matter?

Int J Gynaecol Obstet 2020 Sep 16;150(3):299-305. Epub 2020 Jun 16.

Department of Obstetrics and Gynaecology, St. George's University Hospitals NHS Foundation Trust, London, UK.

Placental dysfunction has a deleterious influence on fetal size and is associated with higher rates of perinatal morbidity and mortality. This association underpins the strategy of fetal size evaluation as a mechanism to identify placental dysfunction and prevent stillbirth. The optimal method of routine detection of small for gestational age (SGA) remains to be clarified with choices between estimation of symphyseal-fundal height versus routine third-trimester ultrasound, various formulae for fetal weight estimation by ultrasound, and the variable use of national, customized, or international fetal growth references. In addition to these controversies, the strategy for detecting SGA is further undermined by data demonstrating that the relationship between fetal size and adverse outcome weakens significantly with advancing gestation such that near term, the majority of stillbirths and adverse perinatal outcomes occur in normally sized fetuses. The use of maternal serum biochemical and Doppler parameters near term appears to be superior to fetal size in the identification of fetuses compromised by placental dysfunction and at increased risk of damage or demise. Multiparameter models and predictive algorithms using maternal risk factors, and biochemical and Doppler parameters have been developed, but need to be prospectively validated to demonstrate their effectiveness.
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http://dx.doi.org/10.1002/ijgo.13229DOI Listing
September 2020

Hypertensive Disorders of Pregnancy and Future Cardiovascular Health.

Front Cardiovasc Med 2020 15;7:59. Epub 2020 Apr 15.

Fetal Medicine Unit, St George's University Hospitals NHS Foundation Trust, University of London, London, United Kingdom.

Hypertensive disorders of pregnancy (HDP) occur in almost 10% of gestations. These women are known to have higher cardiovascular morbidity and mortality later in life in comparison with parous controls who had normotensive pregnancies. Several studies have demonstrated that women with preeclampsia present in a state of segmental impaired myocardial function, biventricular chamber dysfunction, adverse biventricular remodeling, and hypertrophy, a compromised hemodynamic state and indirect echocardiographic signs of localized myocardial ischemia and fibrosis. These cardiac functional and geometric changes are known to have strong predictive value for cardiovascular disease in non-pregnant subjects. A "dose effect" response seems to regulate this relationship with severe HDP, early-onset HDP, coexistence of fetal growth disorders, and recurrence of HDP resulting in poorer cardiovascular measures. The mechanism underlying the relationship between HDP in younger women and cardiovascular disease later in life is unclear but could be explained by sharing of pre-pregnancy cardiovascular risk factors or due to a direct impact of HDP on the maternal cardiovascular system conferring a state of increased susceptibility to future metabolic or hemodynamic insults. If so, the prevention of HDP itself would become all the more urgent. Shortly after delivery, women who experienced HDP express an increased risk of classic cardiovascular risk factors such as essential hypertension, renal disease, abnormal lipid profile, and diabetes with higher frequency than controls. Within one or two decades after delivery, this group of women are more likely to experience premature cardiovascular events, such as symptomatic heart failure, myocardial ischemia, and cerebral vascular disease. Although there is general agreement that women who suffered from HDP should undertake early screening for cardiovascular risk factors in order to allow for appropriate prevention, the exact timing and modality of screening has not been standardized yet. Our findings suggest that prevention should start as early as possible after delivery by making the women aware of their increased cardiovascular risk and encouraging weight control, stop smoking, healthy diet, and daily exercise which are well-established and cost-effective prevention strategies.
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http://dx.doi.org/10.3389/fcvm.2020.00059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7174679PMC
April 2020

Is umbilicocerebral ratio better than cerebroplacental ratio for predicting adverse pregnancy and neonatal outcomes?

Am J Obstet Gynecol 2020 09 18;223(3):462-463. Epub 2020 Apr 18.

Fetal Medicine Unit, St George's Hospital, St George's, University of London, Cranmer Terrace, London SW17 0RE, United Kingdom; Vascular Biology Research Centre, Molecular and Clinical Sciences Research Institute, St George's, University of London, Cranmer Terrace, London SW17 0RE, United Kingdom. Electronic address:

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http://dx.doi.org/10.1016/j.ajog.2020.04.009DOI Listing
September 2020

The role of aspirin in prevention of preeclampsia in twin pregnancies: does the dose matter?

Am J Obstet Gynecol 2020 09 12;223(3):457-458. Epub 2020 Mar 12.

Fetal Medicine Unit, St George's Hospital, St George's University of London; Vascular Biology Research Centre, Molecular and Clinical Sciences Research Institute, St George's University of London, London, United Kingdom. Electronic address:

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http://dx.doi.org/10.1016/j.ajog.2020.03.005DOI Listing
September 2020

Perinatal outcomes of twin pregnancies affected by early twin-twin transfusion syndrome: A systematic review and meta-analysis.

Acta Obstet Gynecol Scand 2020 09 7;99(9):1121-1134. Epub 2020 Apr 7.

Fetal Medicine Unit, St George's Hospital, St George's University of London, London, UK.

Introduction: Twin-to-twin transfusion syndrome (TTTS) is associated with a high risk of perinatal mortality and morbidity if not treated. However, the optimal timing and management in case of early (occurring < 18 weeks) TTTS has not been established yet.

Material And Methods: This is a systematic review and meta-analysis aiming at evaluating the outcomes of monochorionic diamniotic twin pregnancies complicated by early (ie before 18 weeks) TTTS according to different management options (expectant, laser therapy, amnioreduction or cord occlusion). The primary outcome was mortality, including single and double intrauterine, neonatal and perinatal death. Secondary outcomes were: composite morbidity, neuromorbidity, respiratory distress syndrome, admission to neonatal intensive care unit, intact survival (defined as survival free from neurological complications) and preterm birth < 32 weeks of gestation. All outcomes were reviewed according to the different management options (expectant, laser therapy, amnioreduction or cord occlusion) and reported FOR the overall population of twins, and for the donor and recipient separately. Subgroup analysis for TTTS occurring before 16 weeks of gestation was performed. Random-effect meta-analyses of proportions were used to analyse the data.

Results: Thirteen studies were included. Early TTTS occurred in 14.3% (95% confidence interval [CI] 11.9-17.0) of cases. The incidence of intrauterine death was 19.0% (95% CI 2.6-45.5) in twins managed expectantly, 32.4% (95% CI 16.5-50.7) in those who received laser treatment and 12.5% (95% CI 4.8-23.0) in those treated with amnioreduction. The incidence of neonatal death was 22.6% (95% CI 4.2-49.8) in twins managed expectantly, 24.7% (95% CI 0.5-80.3) in those who received laser and 20.2 (95% CI 5.8-43.4) in those who had amnioreduction; it was not possible to compute the incidence of these outcomes in twins undergoing cord occlusion because of insufficient sample and lack of reporting of most of the observed outcomes. Overall, the incidence of perinatal death was 43.9% (95% CI 5.9-87.7) in twins managed expectantly, 47.3% (95% CI 21.4-70.0) in those treated with laser and 28.5% in those who had amnioreduction.

Conclusions: Twin pregnancies affected by early TTTS are at substantial risk of perinatal mortality and morbidity; however, the data come from very small studies with a high risk of selection bias.
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http://dx.doi.org/10.1111/aogs.13840DOI Listing
September 2020

Speckle Tracking Echocardiography: New Ways of Translational Approaches in Preeclampsia to Detect Cardiovascular Dysfunction.

Int J Mol Sci 2020 Feb 10;21(3). Epub 2020 Feb 10.

Experimental and Clinical Research Center, a joint cooperation between the Max - Delbrück-Center for Molecular Medicine and the Charité-Universitätsmedizin Berlin, 13125 Berlin, Germany.

Several studies have shown that women with a preeclamptic pregnancy exhibit an increased risk of cardiovascular disease. However, the underlying molecular mechanisms are unknown. Animal models are essential to investigate the causes of this increased risk and have the ability to assess possible preventive and therapeutic interventions. Using the latest technologies such as speckle tracking echocardiography (STE), it is feasible to map subclinical changes in cardiac diastolic and systolic function as well as structural changes of the maternal heart. The aim of this work is to compare cardiovascular changes in an established transgenic rat model with preeclampsia-like pregnancies with findings from human preeclamptic pregnancies by STE. The same algorithms were used to evaluate and compare the changes in echoes of human and rodents. Parameters of functionality such as global longitudinal strain (animal -23.54 ± 1.82% vs. -13.79 ± 0.57%, human -20.60 ± 0.47% vs. -15.45 ± 1.55%) as well as indications of morphological changes such as relative wall thickness (animal 0.20 ± 0.01 vs. 0.25 ± 0.01, human 0.34 ± 0.01 vs. 0.40 ± 0.02) are significantly altered in both species after preeclamptic pregnancies. Thus, the described rat model simulates the human situation quite well and is a valuable tool for future investigations regarding cardiovascular changes. STE is a unique technique that can be applied in animal models and humans with a high potential to uncover cardiovascular maladaptation and subtle pathologies.
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http://dx.doi.org/10.3390/ijms21031162DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7037420PMC
February 2020

Evidence for uteroplacental malperfusion in fetuses with major congenital heart defects.

PLoS One 2020 5;15(2):e0226741. Epub 2020 Feb 5.

Fetal Medicine Unit, St George's University Hospitals NHS Foundation Trust and Molecular & Clinical Sciences Research Institute, St George's University of London, London, England, United Kingdom.

Aims: Fetuses affected by congenital heart defects (CHD) are considered to be at increased risk of fetal growth restriction and intrauterine demise. Whether these risks are a direct consequence of fetal CHD or a result of associated uteroplacental dysfunction is not evident from the data of recent studies. The aim of this study was to investigate the prevalence of uteroplacental dysfunction reflected by abnormal uterine artery Doppler indices and reduced fetal growth in CHD pregnancies.

Methods: This is a retrospective case-control study including singleton pregnancies referred for detailed fetal cardiac assessment subsequently diagnosed with or without CHD. Mid-trimester uterine artery Doppler assessment at 20-24 weeks as well as third trimester fetal biometry and arterial Doppler pulsatility indices (PI) were performed. All fetal biometry were converted into centiles and Doppler values to multiples of median (MoM) to adjust for physiological changes with gestation.

Results: The study included 811 pregnancies including 153 cases where the fetus was diagnosed with CHD. Mid-pregnancy uterine artery PI was significantly higher in women with fetal CHD compared to controls (0.90MoM vs 0.83MoM; p = 0.006). In the third trimester, median centiles for fetal head circumference (45.4 vs 57.07; p<0.001), abdominal circumference (51.17 vs 55.71; p = 0.014), estimated fetal weight (33.6 vs 56.7; p<0.001) and cerebroplacental ratio (CPR: 0.84MoM vs 0.95MoM; p<0.001) were significantly lower in fetuses with CHD compared to controls. The percentage of small for gestational age births <10th centile (24.0% vs 10.7%; <0.001) and low CPR <0.6MoM (11.7% vs 2.5%; p<0.001) were significantly higher in the fetal CHD cohort.

Conclusions: Mid-pregnancy uterine artery resistance is increased and subsequent fetal biometry reduced in pregnancies with CHD fetuses. These findings suggest that fetal CHD are associated with uteroplacental dysfunction, secondary to impaired maternal uteroplacental perfusion resulting in relative fetal hypoxaemia and reduced fetal growth.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0226741PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7001956PMC
April 2020

Angiogenic Marker Prognostic Models in Pregnant Women With Hypertension.

Hypertension 2020 03 27;75(3):755-761. Epub 2020 Jan 27.

From the Fetal Medicine Unit, St George's Hospital, St George's University of London, United Kingdom (H.P., E.K., B.T., A.K.).

Angiogenic markers such as PlGF (placental growth factor) and sFlt-1 (soluble Fms-like tyrosine kinase-1) have been shown to be useful for predicting adverse outcome in women suspected of having preeclampsia. The aim of the current study was to evaluate the prognostic value of angiogenic markers and maternal risk factors in pregnant women with hypertension. This was a prospective study of pregnancies complicated by preeclampsia, gestational hypertension, or chronic hypertension presenting to 1 of 2 tertiary referral hospitals between May 2013 and May 2018. Maternal characteristics along with blood samples for angiogenic marker analysis were obtained from participants. The primary outcome was delivery related to preeclampsia within 1 and 2 weeks. In total, 302 women with hypertension were included in the study cohort. The baseline model included maternal body mass index, mean arterial pressure, and clinical diagnosis at the time of assessment. The use of sFlt-1/PIGF ratio combined with the baseline model significantly improved the area under the curve values for predicting delivery within a week (0.83 versus 0.88; =0.025) or in 2 weeks (0.86 versus 0.93; =0.001) due to preeclampsia-related events in gestational ages <35 weeks. The magnitude of increase in accuracy was 7.9% (-0.5% to 16.4%, posterior probability of increase: 96.7%) for sFlt-1/PlGF ratio. Our results emphasize the additive value of angiogenic biomarkers and the superior performance of a continuous scale of sFlt-1/PlGF ratio in the model. The added utility of angiogenic markers diminishes after 35 weeks' gestation.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.119.13997DOI Listing
March 2020

Preeclampsia: the role of persistent endothelial cells in uteroplacental arteries. Brosens I, Brosens JJ, Muter J, Puttemans P, Benagiano G. Am J Obstet Gynecol 2019;221:219-26.

Am J Obstet Gynecol 2020 06 22;222(6):633. Epub 2020 Jan 22.

Professor Fetal Maternal Medicine, Fetal Medicine Unit, St George's University Hospitals NHS Foundation Trust, London, United Kingdom.

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http://dx.doi.org/10.1016/j.ajog.2019.12.274DOI Listing
June 2020

Home blood pressure monitoring in the antenatal and postpartum period: A systematic review meta-analysis.

Pregnancy Hypertens 2020 Jan 2;19:44-51. Epub 2020 Jan 2.

Fetal Medicine Unit, St George's University Hospitals NHS Foundation Trust, Blackshaw Road, London SW17 0RE, UK; Vascular Biology Research Centre, Molecular and Clinical Sciences Research Institute, St George's University of London, London SW17 0RE, UK. Electronic address:

Recent evidence suggests that home blood pressure monitoring (HBPM) is an effective way of managing women with hypertensive disorders of pregnancy (HDP) without increasing adverse outcomes. The aim of this systematic review and meta-analysis was to investigate the safety and efficacy of HBPM during pregnancy. Medline, EMBASE and the Cochrane library databases were searched electronically in November 2018. Studies were included from which data could be extracted on the pregnancy outcomes and included pregnancies with HDP or at increased risk of developing HDP. Data from nine studies were included in the meta-analysis. The use of HBPM during the antenatal period was associated with reduced risk of induction of labor (OR: 0.55, 95% CI: 0.36-0.82, 444 women, I = 0%), prenatal hospital admissions (OR: 0.31, 95% CI: 0.19-0.49, 416 women, I = 0%) and diagnosis of preeclampsia (OR: 0.50, 95% CI: 0.31-0.81, 725 women, I = 37%). The number of antenatal visits was significantly less in the HBPM group (standard mean difference: -0.49, 95% CI: -0.82 to -0.16, 738 women, I = 75%). There were no significant differences between HBPM and conventional care regarding composite maternal, fetal or neonatal outcomes when used during the antenatal period. There were no significant differences between the groups who had HBPM compared to those who had conventional care regarding postpartum readmissions and obtaining a blood pressure measurement within 10 days of delivery after discharge. The significant clinical heterogeneity and low quality of evidence are the main limitations, and therefore, more high quality studies are needed.
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http://dx.doi.org/10.1016/j.preghy.2019.12.001DOI Listing
January 2020

Statins Reverse Postpartum Cardiovascular Dysfunction in a Rat Model of Preeclampsia.

Hypertension 2020 01 2;75(1):202-210. Epub 2019 Dec 2.

From the Experimental and Clinical Research Center-a joint cooperation between the Max Delbrück Center for Molecular Medicine and the Charité-Universitätsmedizin Berlin, Germany (K.K., F.H., M.G., S.G., A.B., D.N.M., R.D., N.H.).

Preeclampsia is associated with increased cardiovascular long-term risk; however, the underlying functional and structural mechanisms are unknown. We investigated maternal cardiac alterations after preeclampsia. Female rats harboring the human angiotensinogen gene [TGR(hAogen)L1623] develop a preeclamptic phenotype with hypertension and albuminuria during pregnancy when mated with male rats bearing the human renin gene [TGR(hRen)L10J] but behave physiologically normal before and after pregnancy. Furthermore, rats were treated with pravastatin. We tested the hypothesis that statins are a potential therapeutic intervention to reduce cardiovascular alterations due to simulated preeclamptic pregnancy. Although hypertension persists for only 8 days in pregnancy, former preeclampsia rats exhibit significant cardiac hypertrophy 28 days after pregnancy observed in both speckle tracking echocardiography and histological staining. In addition, fibrosis and capillary rarefaction was evident. Pravastatin treatment ameliorated the remodeling and improved cardiac output postpartum. Preeclamptic pregnancy induces irreversible structural changes of cardiac hypertrophy and fibrosis, which can be moderated by pravastatin treatment. This pathological cardiac remodeling might be involved in increased cardiovascular risk in later life.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.119.13219DOI Listing
January 2020

Ductus venosus Doppler waveform pattern in fetuses with early growth restriction.

Acta Obstet Gynecol Scand 2020 05 22;99(5):608-614. Epub 2019 Dec 22.

Fetal Medicine Unit, St George's University Hospitals NHS Foundation Trust and Molecular & Clinical Sciences Research Institute, St George's University, London, UK.

Introduction: We aimed to assess if maximum velocities of the ductus venosus flow velocity waveform are associated with adverse outcomes in early-onset fetal growth restriction.

Material And Methods: Retrospective cohort study from two tertiary referral units, including singleton fetuses with estimated birthweight or fetal abdominal circumference ≤10th centile and absent or reversed end-diastolic velocity in the umbilical artery delivered between 26 and 34  weeks of gestation. Pulsatility index for veins, and maximum velocities of S-, D-, v- and a-waves, were measured in the ductus venosus within 24 hours of birth. Logistic regression was used to describe the relation between severe neonatal morbidity or neonatal death and clinical independent predictors.

Results: The study population included 132 early-onset fetal growth restriction fetuses. Newborns with neonatal morbidity or neonatal death had significantly lower values of v/D maximum velocity ratio multiples of the median (0.86 vs 095; P = 0.006) within 24 hours of birth. The v/D ratio remained a significant predictor of neonatal death or severe neonatal morbidity after adjusting for gestational age and birthweight (adjusted odds ratio 0.065, 95% confidence interval 0.004-0.957).

Conclusions: Assessment of ductus venosus v/D maximum velocity ratio might help to identify fetal growth restriction fetuses at increased risk for neonatal death or severe neonatal morbidity. Confirmation in prospective studies is necessary.
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http://dx.doi.org/10.1111/aogs.13782DOI Listing
May 2020

Preventing term stillbirth: benefits and limitations of using fetal growth reference charts.

Curr Opin Obstet Gynecol 2019 12;31(6):365-374

Department of Obstetrics and Gynaecology, St. George Hospital University Medical Center, Beirut, Lebanon.

Purpose Of Review: This review examines the variation in clinical practice with regards to ultrasound estimation of fetal weight, as well as calculation of fetal weight centiles.

Recent Findings: Placental dysfunction is associated with fetal smallness from intrauterine malnutrition as well as fetal disability and even stillbirth from hypoxemia. Although estimating fetal weight can be done accurately, the issue of which fetal weight centile chart should be used continues to be a contentious topic. The arguments against local fetal growth charts based on national borders and customization for variables known to be associated with disease are substantial. As for other human diseases such as hypertension and diabetes, there is a rationale for the use of an international fetal growth reference standard. Irrespective of the choice of fetal growth reference standard, a significant limitation of small for gestational age (SGA) detection programs to prevent stillbirth is that the majority of stillborn infants at term were not SGA at the time of demise.

Summary: Placental dysfunction can present with SGA from malnutrition and/or stillbirth from hypoxemia depending on the gestational age of onset. Emerging data show that at term, fetal Doppler arterial redistribution is associated more strongly with perinatal death than fetal size. Properly conducted trials of the role for maternal characteristics, fetal size, placental biomarkers, and Doppler assessing fetal well-being are required urgently.
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http://dx.doi.org/10.1097/GCO.0000000000000576DOI Listing
December 2019

Pregnancy outcomes following home blood pressure monitoring in gestational hypertension.

Pregnancy Hypertens 2019 Oct 15;18:14-20. Epub 2019 Jul 15.

Middle East Technical University, Department of Statistics, Ankara, Turkey; Molecular & Clinical Sciences Research Institute, St. George's University of London, London, UK. Electronic address:

Objectives: To assess the safety and efficacy of home blood pressure monitoring (HBPM) and office (traditional) blood pressure measurements in a cohort of pregnant women with gestational hypertension (GH).

Study Design: This was a cohort study at St. George's Hospital, University of London conducted between December 2013 and August 2018. The inclusion criteria was pregnant women with a diagnosis of GH. Eligible patients were counseled and trained by a specialist midwife and were provided with an automated Microlife® "WatchBP Home" BP machine. Each patient followed an individualised schedule of hospital visits and BP measurements based on the HBPM pathway or standard hospital protocol which was based on the National Institute of Health and Care Excellence (NICE) guideline.

Main Outcome Measures: Adverse fetal, neonatal and maternal outcomes as well as number of antenatal hospital visits were recorded and compared between HBPM and office (traditional) pathways.

Results: 143 women with GH were included in the study (80 HBPM vs 63 standard care). There were no significant difference between the two groups in maternal high-dependency unit admission (P = 0.999), birth weight centile (P = 0.803), fetal growth restriction (p = 0.999), neonatal intensive care unit admissions (p = 0.507) and composite neonatal (p = 0.654), maternal (p = 0.999) or fetal adverse outcomes (p = 0.999). The number of Day Assessment Unit (DAU) visits was significantly lower in the HBPM group than the traditional pathway (median 4.0 vs. 5.0, P = 0.009). The difference was greater when the number of visits were adjusted for the duration of monitoring in weeks (median: 1.0 vs 1.5, P < 0.001). There were no significant difference between the two groups in the total number of outpatient (P = 0.357) and triage visits (p = 0.237). However, the total number of antenatal visits adjusted for the duration of monitoring was significantly lower for the HBPM group compared to the traditional pathway (median 1.4 vs 1.8, P = 0.020).

Conclusions: HBPM in women with GH results in significantly less antenatal visits compared to women on a standard pathway of care. The two groups had comparable fetal, neonatal and maternal adverse outcomes. Large multicentre studies are needed to ascertain the safety of rare adverse pregnancy outcomes.
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http://dx.doi.org/10.1016/j.preghy.2019.07.006DOI Listing
October 2019

Ovarian Control of Maternal Cardiovascular Function.

Hypertension 2019 09 29;74(3):507-508. Epub 2019 Jul 29.

From the Vascular Biology Research Centre, Molecular and Clinical Sciences Research Institute, St George's University of London, Cranmer Terrace, United Kingdom; and Fetal Medicine Unit, Department of Obstetrics and Gynaecology, St. George's University Hospitals NHS Foundation Trust, Blackshaw Road, London, United Kingdom.

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http://dx.doi.org/10.1161/HYPERTENSIONAHA.119.13167DOI Listing
September 2019

Intervendor Discordance of Fetal and Neonatal Myocardial Tissue Doppler and Speckle-Tracking Measurements.

J Am Soc Echocardiogr 2019 10 24;32(10):1339-1349.e23. Epub 2019 Jul 24.

Molecular and Clinical Sciences Research Institute, St. George's University of London, London, United Kingdom; Fetal Medicine Unit, St. George's University of London, London, United Kingdom.

Background: Fetal and neonatal studies report a wide range of cardiac parameters derived by pulsed-wave Doppler tissue imaging (DTI) and two-dimensional speckle-tracking echocardiographic (STE) imaging. The use of different ultrasound systems and their vendor-specific software compromises the ability to compare echocardiographic findings among various studies. The aim of this study was to evaluate intervendor reproducibility as well as intra- and interobserver repeatability of DTI and STE measurements in normal-term fetuses and neonates.

Methods: A prospective study was conducted of term fetuses (n = 196) from uncomplicated pregnancies assessed days before the onset of labor and a few hours after birth. Fetal and neonatal DTI and STE parameters were obtained and analyzed using vendor-specific software on three ultrasound systems: Toshiba Aplio MX versus GE Vivid E9 and GE Vivid E9 versus Philips EPIQ. A reproducibility study in fetuses and neonates (n = 118) was performed by systematic scanning with head-to-head comparison.

Results: DTI reproducibility showed moderate to good correlation, with good agreement for fetuses and neonates on Toshiba versus GE (intraclass correlation coefficient [ICC] = 0.4-0.8). Correlation of DTI measurements on GE versus Philips was poor to moderate for fetuses (ICC = 0.1-0.6) and moderate to good for neonates (ICC = 0.5-0.8), with wider limits of agreement. Fetal and neonatal STE parameters revealed very poor correlation (ICC = 0.1-0.3) and agreement among ultrasound vendors. Intra- and interobserver repeatability demonstrated good to excellent correlation of all fetal and neonatal DTI and STE measurements, with good agreement irrespective of the ultrasound platform used.

Conclusions: These findings demonstrate reliable assessment of fetal and neonatal DTI and STE measurements when performed on the same ultrasound platform, whereas ultrasound machines and software from different vendors give significantly divergent estimates of DTI and STE parameters in fetuses and neonates. These intervendor discrepancies have significant clinical and research implications and should be considered when interpreting and comparing study findings, establishing reference standards, or performing systematic reviews.
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http://dx.doi.org/10.1016/j.echo.2019.05.023DOI Listing
October 2019

Preeclampsia: a gestational cardiorenal syndrome.

J Physiol 2019 09 14;597(18):4695-4714. Epub 2019 Aug 14.

Fetal Medicine Unit, St George's University Hospitals NHS Foundation Trust, UK.

It is generally accepted today that there are two different types of preeclampsia: an early-onset or placental type and a late-onset or maternal type. In the latent phase, the first one presents with a low output/high resistance circulation eventually leading in the late second or early third trimester to an intense and acutely aggravating systemic disorder with an important impact on maternal and neonatal mortality and morbidity; the other type presents initially as a high volume/low resistance circulation, gradually evolving to a state of circulatory decompensation usually in the later stages of pregnancy, with a less severe impact on maternal and neonatal outcome. For both processes, numerous dysfunctions of the heart, kidneys, arteries, veins and interconnecting systems are reported, most of them presenting earlier and more severely in early- than in late-onset preeclampsia; however, some very specific dysfunctions exist for either type. Experimental, clinical and epidemiological observations before, during and after pregnancy are consistent with gestation-induced worsening of subclinical pre-existing chronic cardiovascular dysfunction in early-onset preeclampsia, and thus sharing the pathophysiology of cardiorenal syndrome type II, and with acute volume overload decompensation of the maternal circulation in late-onset preeclampsia, thus sharing the pathophysiology of cardiorenal syndrome type 1. Cardiorenal syndrome type V is consistent with the process of preeclampsia superimposed upon clinical cardiovascular and/or renal disease, alone or as part of a systemic disorder. This review focuses on the specific differences in haemodynamic dysfunctions between the two types of preeclampsia, with special emphasis on the interorgan interactions between heart and kidneys, introducing the theoretical concept that the pathophysiological processes of preeclampsia can be regarded as the gestational manifestations of cardiorenal syndromes.
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http://dx.doi.org/10.1113/JP274893DOI Listing
September 2019