Imperial College London

Professor Christoph Lees, MD FRCOG

Faculty of MedicineDepartment of Metabolism, Digestion and Reproduction

Professor of Obstetrics
 
 
 
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Contact

 

c.lees

 
 
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Assistant

 

Ms Rocio Lale-Montes +44 (0)20 7594 2104

 
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Location

 

Queen Charlottes and Chelsea HospitalHammersmith Campus

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Summary

 

Publications

Publication Type
Year
to

382 results found

Familiari A, Napolitano R, Visser GHA, Lees C, Wolf H, Prefumo F, TRUFFLE 2 Feasibility Study investigatorset al., 2022, Antenatal corticosteroids and perinatal outcome in late fetal growth restriction: analysis of prospective cohort., Ultrasound Obstet Gynecol

OBJECTIVE: The aim of this study is to evaluate the possible role of antenatal administration of corticosteroids for fetal lung maturation on short term perinatal outcomes in late FGR. METHODS: This cohort study is a secondary analysis of a multicenter prospective observational study, the TRUFFLE-2 feasibility study, conducted between 2017 and 2018 in 33 European perinatal centers. We included women with singleton pregnancy from 32+0 to 36+6 weeks of gestation with a fetus considered at risk for FGR, defined as estimated fetal weight (EFW) or abdominal circumference (AC) <10th centile, or umbilico-cerebral ratio (UCR) >95th centile, or a fall of more than 40 centile points in AC measurement from the 20 weeks scan. The primary adverse outcome was a composite of abnormal condition at birth or major neonatal morbidity. RESULTS: A total of 86 pregnancies who received antenatal corticosteroids (exposed) were matched with non-exposed pregnancies. Both groups were similar regarding gestational age at inclusion (33 weeks), EFW (1673 g) and UCR (0.68), gestational age at delivery (35.5 weeks) and birth weight (1925 g); the presented values are for both groups combined. No significant differences were observed between exposed and non-exposed for composite adverse outcome (28% vs. 24%; p=0.73) or for any of its elements. CONCLUSION: The present data do not show a beneficial effect of steroids on short term outcomes in fetuses with late FGR. This article is protected by copyright. All rights reserved.

Journal article

Dennehy N, Lees C, 2022, Preeclampsia: Maternal cardiovascular function and optimising outcomes, EARLY HUMAN DEVELOPMENT, Vol: 174, ISSN: 0378-3782

Journal article

Zielinska AP, Mullins E, Magni E, Zamagni G, Kleprlikova H, Adams O, Stampalija T, Monasta L, Lees Cet al., 2022, Remote multimodality monitoring of maternal physiology from the first trimester to postpartum period: study results., Journal of Hypertension, Vol: 40, Pages: 2280-2291, ISSN: 0263-6352

OBJECTIVES: Current antenatal care largely relies on widely spaced appointments, hence only a fraction of the pregnancy period is subject to monitoring. Continuous monitoring of physiological parameters could represent a paradigm shift in obstetric care. Here, we analyse the data from daily home monitoring in pregnancy and consider the implications of this approach for tracking pregnancy health. METHODS: Prospective feasibility study of continuous home monitoring of blood pressure, weight, heart rate, sleep and activity patterns from the first trimester to 6 weeks postpartum. RESULTS: Fourteen out of 24 women completed the study (58%). Compared to early pregnancy [week 13, median heart rate (HR) 72/min, interquartile range (IQR) 12.8], heart rate increased by week 35 (HR 78/min, IQR 16.6; P = 0.041) and fell postpartum (HR 66/min, IQR 11.5, P = 0.021). Both systolic and diastolic blood pressure were lower at mid-gestation (week 20: SBP 103 mmHg, IQR 6.6; DPB 63 mmHg, IQR 5.3 P = 0.005 and P = 0.045, respectively) compared to early pregnancy (week 13, SBP 107 mmHg, IQR 12.4; DPB 67 mmHg, IQR 7.1). Weight increased during pregnancy between each time period analyzed, starting from week 15. Smartwatch recordings indicated that activity increased in the prepartum period, while deep sleep declined as pregnancy progressed. CONCLUSION: Home monitoring tracks individual physiological responses to pregnancy in high resolution that routine clinic visits cannot. Changes in the study protocol suggested by the study participants may improve compliance for future studies, which was particularly low in the postpartum period. Future work will investigate whether distinct adaptative patterns predate obstetric complications, or can predict long-term maternal cardiovascular health.

Journal article

Relph S, Vieira MC, Copas A, Coxon K, Alagna A, Briley A, Johnson M, Page L, Peebles D, Shennan A, Thilaganathan B, Marlow N, Lees C, Lawlor DA, Khalil A, Sandall J, Pasupathy D, Healey A, on behalf of the DESiGN Trial Teamet al., 2022, Improving antenatal detection of small-for-gestational-age fetus: economic evaluation of Growth Assessment Protocol., Ultrasound Obstet Gynecol, Vol: 60, Pages: 620-631

OBJECTIVE: To determine whether the Growth Assessment Protocol (GAP), as implemented in the DESiGN trial, is cost-effective in terms of antenatal detection of small-for-gestational-age (SGA) neonate, when compared with standard care. METHODS: This was an incremental cost-effectiveness analysis undertaken from the perspective of a UK National Health Service hospital provider. Thirteen maternity units from England, UK, were recruited to the DESiGN (DEtection of Small for GestatioNal age fetus) trial, a cluster randomized controlled trial. Singleton, non-anomalous pregnancies which delivered after 24 + 0 gestational weeks between November 2015 and February 2019 were analyzed. Probabilistic decision modeling using clinical trial data was undertaken. The main outcomes of the study were the expected incremental cost, the additional number of SGA neonates identified antenatally and the incremental cost-effectiveness ratio (ICER) (cost per additional SGA neonate identified) of implementing GAP. Secondary analysis focused on the ICER per infant quality-adjusted life year (QALY) gained. RESULTS: The expected incremental cost (including hospital care and implementation costs) of GAP over standard care was £34 559 per 1000 births, with a 68% probability that implementation of GAP would be associated with increased costs to sustain program delivery. GAP identified an additional 1.77 SGA neonates per 1000 births (55% probability of it being more clinically effective). The ICER for GAP was £19 525 per additional SGA neonate identified, with a 44% probability that GAP would both increase cost and identify more SGA neonates compared with standard care. The probability of GAP being the dominant clinical strategy was low (11%). The expected incremental cost per infant QALY gained ranged from £68 242 to £545 940, depending on assumptions regarding the QALY value of detection of SGA. CONCLUSION: The economic case f

Journal article

Hodgetts Morton V, Toozs-Hobson P, Moakes CA, Middleton L, Daniels J, Simpson NAB, Shennan A, Israfil-Bayli F, Ewer AK, Gray J, Slack M, Norman JE, Lees C, Tryposkiadis K, Hughes M, Brocklehurst P, Morris RKet al., 2022, Monofilament suture versus braided suture thread to improve pregnancy outcomes after vaginal cervical cerclage (C-STICH): a pragmatic randomised, controlled, phase 3, superiority trial., Lancet, Vol: 400, Pages: 1426-1436

BACKGROUND: Miscarriage in the second trimester and preterm birth are significant global problems. Vaginal cervical cerclage is performed to prevent pregnancy loss and preterm birth. We aimed to determine the effectiveness of a monofilament suture thread compared with braided suture thread on pregnancy loss rates in women undergoing a cervical cerclage. METHODS: C-STICH was a pragmatic, randomised, controlled, superiority trial done at 75 obstetric units in the UK. Women with a singleton pregnancy who received a vaginal cervical cerclage due to a history of pregnancy loss or premature birth, or if indicated by ultrasound, were centrally randomised (1:1) using minimisation to receive a monofilament suture or braided suture thread for their cervical cerclage. Women and outcome assessors were masked to allocation as far as possible. The primary outcome was pregnancy loss, defined as miscarriage, stillbirth, or neonatal death in the first week of life, analysed in the intention-to-treat population (ie, all women who were randomly assigned). Safety was also assessed in the intention-to-treat population. The trial was registered with ISRCTN, ISRCTN15373349. FINDINGS: Between Aug 21, 2015, and Jan 28, 2021, 2049 women were randomly assigned to receive a monofilament suture (n=1025) or braided suture (n=1024). The primary outcome was ascertained in 1003 women in the monofilament suture group and 993 women in the braided suture group. Pregnancy loss occurred in 80 (8·0%) of 1003 women in the monofilament suture group and 75 (7·6%) of 993 women in the braided suture group (adjusted risk ratio 1·05 [95% CI 0·79 to 1·40]; adjusted risk difference 0·002 [95% CI -0·02 to 0·03]). INTERPRETATION: Monofilament suture did not reduce rate of pregnancy loss when compared with a braided suture. Clinicians should use the results of this trial to facilitate discussions around the choice of suture thread to optimise outcomes. FUNDING:

Journal article

Fantasia I, Zamagni G, Lees C, Mylrea-Foley B, Monasta L, Mullins E, Prefumo F, Stampalija Tet al., 2022, Current practice in the diagnosis and management of fetal growth restriction: An international survey, Acta Obstetricia et Gynecologica Scandinavica, ISSN: 0001-6349

IntroductionThe aim of this survey was to evaluate the current practice in respect of diagnosis and management of fetal growth restriction among obstetricians in different countries.Material and methodsAn e-questionnaire was sent via REDCap with “click thru” links in emails and newsletters to obstetric practitioners in different countries and settings with different levels of expertise. Clinical scenarios in early and late fetal growth restriction were given, followed by structured questions/response pairings.ResultsA total of 275 participants replied to the survey with 87% of responses complete. Participants were obstetrician/gynecologists (54%; 148/275) and fetal medicine specialists (43%; 117/275), and the majority practiced in a tertiary teaching hospital (56%; 153/275). Delphi consensus criteria for fetal growth restriction diagnosis were used by 81% of participants (223/275) and 82% (225/274) included a drop in fetal growth velocity in their diagnostic criteria for late fetal growth restriction. For early fetal growth restriction, TRUFFLE criteria were used for fetal monitoring and delivery timing by 81% (223/275). For late fetal growth restriction, indices of cerebral blood flow redistribution were used by 99% (250/252), most commonly cerebroplacental ratio (54%, 134/250). Delivery timing was informed by cerebral blood flow redistribution in 72% (176/244), used from ≥32 weeks of gestation. Maternal biomarkers and hemodynamics, as additional tools in the context of early-onset fetal growth restriction (≤32 weeks of gestation), were used by 22% (51/232) and 46% (106/230), respectively.ConclusionsThe diagnosis and management of fetal growth restriction are fairly homogeneous among different countries and levels of practice, particularly for early fetal growth restriction. Indices of cerebral flow distribution are widely used in the diagnosis and management of late fetal growth restriction, whereas maternal biomarkers and hemodynam

Journal article

Relph S, Vieira MC, Copas A, Alagna A, Page L, Winsloe C, Shennan A, Briley A, Johnson M, Lees C, Lawlor DA, Sandall J, Khalil A, Pasupathy D, DESiGN Trial Team and DESiGN Collaborative Groupet al., 2022, Characteristics associated with antenatally unidentified small-for-gestational-age fetuses: prospective cohort study nested within the DESiGN randomized control trial., Ultrasound Obstet Gynecol

OBJECTIVE: To identify the clinical characteristics and patterns of ultrasound use amongst pregnancies with antenatally unidentified SGA, compared to those in which it is identified, to understand how to better design interventions that improve antenatal SGA identification. METHODS: A prospective cohort study of singleton, non-anomalous, small for gestational age (SGA, birthweight<10th centile) babies born after 24+0 gestational weeks, from 13 UK sites, collected for the baseline period and control arm of the DESiGN trial. We define pregnancies with antenatally unidentified SGA where there was no scan or a final scan with estimated fetal weight, EFW, at 10th centile or above; and as identified SGA if EFW was below 10th centile at last scan. Maternal and fetal sociodemographic and clinical characteristics were studied for associations with unidentified SGA using unadjusted and adjusted logistic regression models. Ultrasound parameters (gestational age at first growth scan, ultrasound frequency, duration between the last scan and the birth, absolute centile difference between the last scan and the birth) were described and associations with missed SGA were also studied by unadjusted and adjusted logistic regression but stratified by presence of indications for serial ultrasound. RESULTS: Of the 15,784 SGA babies included, SGA was not identified antenatally in 78.7%. Of pregnancies with unidentified SGA, 47.1% had no recorded growth scan. Amongst 9,410 pregnancies with complete data on key maternal co-morbidities and antenatal complications, the risk of unidentified SGA was lower for women with any indication for serial scans (aOR 0.56, 95% CI: 0.49-0.64), Asian ethnicity (aOR 0.80 compared to white, 95% CI: 0.69-0.93) and non-cephalic presentation (aOR 0.58, 95% CI: 0.46-0.73). The risk of unidentified SGA was highest among women with BMI 25.0-29.9 kg/m2 (aOR 1.15 compared to 18.5-24.9 kg/m2 , 95% CI: 1.01-1.32) and lowest in those with underweight BMI (aOR 0.61, 9

Journal article

Oyelese Y, Lees CC, Jauniaux E, 2022, The case for screening for vasa previa: time to implement a life-saving strategy., Ultrasound Obstet Gynecol

Journal article

Relph S, Coxon K, Vieira MC, Copas A, Healey A, Alagna A, Briley A, Johnson M, Lawlor DA, Lees C, Marlow N, McCowan L, McMicking J, Page L, Peebles D, Shennan A, Thilaganathan B, Khalil A, Pasupathy D, Sandall Jet al., 2022, Effect of the Growth Assessment Protocol on the DEtection of Small for GestatioNal age fetus: process evaluation from the DESiGN cluster randomised trial, IMPLEMENTATION SCIENCE, Vol: 17, ISSN: 1748-5908

Journal article

Khalil A, Samara A, O'Brien P, Morris E, Draycott T, Lees C, Ladhani Set al., 2022, Monkeypox vaccines in pregnancy: lessons must be learned from COVID-19, The Lancet Global Health, Vol: 10, Pages: e1230-e1231, ISSN: 2214-109X

Journal article

Jaspal R, Allen M, Cornette J, Rizopoulos D, Lees Cet al., 2022, Validation of non-invasive measurements of cardiac output: using whole body bio-impedance versus inert gas rebreathing in healthy women undergoing in vitro fertilisation, Artery Research, Vol: 28, Pages: 100-104, ISSN: 1872-9312

Background:Haemodynamic assessment in and before pregnancy is becoming increasingly important in relation to pregnancy complications and outcomes. Different methodologies exist but there is no gold-standard technique for non-invasive measurement of cardiac output (CO). We sought to assess two methods of CO measurement in healthy women undergoing In Vitro Fertilisation Cycles (IVF). This was a prospective longitudinal study of 71 women aged 18-44yrs planning IVF undergoing CO measurements obtained via Inert Gas rebreathing (IGR) using InnocorTM and whole-body bio-impedance (WBI) using NicasTM in order to assess the reproducibility between the methods. Four visits occurred at which both techniques were used: initial assessment, embryo transfer, day of pregnancy test and 4 weeks post transfer (regardless of whether conception occurred).Cross-sectional agreement of the methods was assessed using the calculation of bias, percentage error and Limits of Agreement (LOA) via the Bland-Altman analysis. Longitudinal agreement of the methods was assessed using a 4-quadrant plot with concordance rate, angular bias and radial limits of agreement (%).Results:113 measurements from 44 participants were suitable for cross-sectional (Bland-Altman) analysis. IGR (InnocorTM) Mean CO was 4.61 L/min and 5.05 L/min with WBI (NicasTM). The bias was 0.44L/min. The percentage error was 76% and intra-correlation coefficient was 0.135 (95%CI -0.43 – 0.306).59 measurements from 28 participants were suitable for longitudinal (4Q-plot) analysis. The concordance rate was 64.4 %, angular bias -0.14, radial limits of agreement +- 13.25°.Conclusions:There was poor cross-sectional and longitudinal agreement between inert gas rebreathing and whole-body bio- impedance techniques. These techniques cannot be used interchangeably when measuring CO in women undergoing IVF, and these results may be more generalizable.

Journal article

Smith ER, Oakley E, Grandner GW, Rukundo G, Farooq F, Ferguson K, Baumann S, Waldorf KA, Afshar Y, Ahlberg M, Ahmadzia H, Akelo V, Aldrovandi G, Bevilacqua E, Bracero N, Brandt JS, Broutet N, Carrillo J, Conry J, Cosmi E, Crispi F, Crovetto F, Gil MDM, Delgado-López C, Divakar H, Driscoll AJ, Favre G, Buhigas IF, Flaherman V, Gale C, Godwin CL, Gottlieb S, Gratacós E, He S, Hernandez O, Jones S, Joshi S, Kalafat E, Khagayi S, Knight M, Kotloff K, Lanzone A, Longo VL, Le Doare K, Lees C, Litman E, Lokken EM, Madhi SA, Magee LA, Martinez-Portilla RJ, Metz TD, Miller ES, Money D, Moungmaithong S, Mullins E, Nachega JB, Nunes MC, Onyango D, Panchaud A, Poon LC, Raiten D, Regan L, Sahota D, Sakowicz A, Sanin-Blair J, Stephansson O, Temmerman M, Thorson A, Thwin SS, Tippett Barr BA, Tolosa JE, Tug N, Valencia-Prado M, Visentin S, von Dadelszen P, Whitehead C, Wood M, Yang H, Zavala R, Tielsch JMet al., 2022, Clinical risk factors of adverse outcomes among women with COVID-19 in the pregnancy and postpartum period: A sequential, prospective meta-analysis, American Journal of Obstetrics and Gynecology, ISSN: 0002-9378

OBJECTIVE: This sequential, prospective meta-analysis (sPMA) sought to identify risk factors among pregnant and postpartum women with COVID-19 for adverse outcomes related to: disease severity, maternal morbidities, neonatal mortality and morbidity, adverse birth outcomes. DATA SOURCES: We prospectively invited study investigators to join the sPMA via professional research networks beginning in March 2020. STUDY ELIGIBILITY CRITERIA: Eligible studies included those recruiting at least 25 consecutive cases of COVID-19 in pregnancy within a defined catchment area. STUDY APPRAISAL AND SYNTHESIS METHODS: We included individual patient data from 21 participating studies. Data quality was assessed, and harmonized variables for risk factors and outcomes were constructed. Duplicate cases were removed. Pooled estimates for the absolute and relative risk of adverse outcomes comparing those with and without each risk factor were generated using a two-stage meta-analysis. RESULTS: We collected data from 33 countries and territories, including 21,977 cases of SARS-CoV-2 infection in pregnancy or postpartum. We found that women with comorbidities (pre-existing diabetes, hypertension, cardiovascular disease) versus those without were at higher risk for COVID-19 severity and pregnancy health outcomes (fetal death, preterm birth, low birthweight). Participants with COVID-19 and HIV were 1.74 times (95% CI: 1.12, 2.71) more likely to be admitted to the ICU. Pregnant women who were underweight before pregnancy were at higher risk of ICU admission (RR 5.53, 95% CI: 2.27, 13.44), ventilation (RR 9.36, 95% CI: 3.87, 22.63), and pregnancy-related death (RR 14.10, 95% CI: 2.83, 70.36). Pre-pregnancy obesity was also a risk factor for severe COVID-19 outcomes including ICU admission (RR 1.81, 95% CI: 1.26,2.60), ventilation (RR 2.05, 95% CI: 1.20,3.51), any critical care (RR 1.89, 95% CI: 1.28,2.77), and pneumonia (RR 1.66, 95% CI: 1.18,2.33). Anemic pregnant women with COVID-19 also had in

Journal article

Valensise H, Farsetti D, Pometti F, Vasapollo B, Novelli GP, Lees Cet al., 2022, The cardiac-fetal-placental unit: fetal umbilical vein flow rate is linked to the maternal cardiac profile in fetal growth restriction., Am J Obstet Gynecol

BACKGROUND: The functional maternal-fetal hemodynamic unit includes fetal umbilical vein flow and maternal peripheral vascular resistance. OBJECTIVE: This study investigated the relationships between maternal and fetal hemodynamics in a population with suspected fetal growth restriction. STUDY DESIGN: This was a prospective study of normotensive pregnancies referred to our outpatient clinic for a suspected fetal growth restriction. Maternal hemodynamics measurement was performed, using a noninvasive device (USCOM-1A) and a fetal ultrasound evaluation to assess fetal biometry and velocimetry Doppler parameters. Comparisons among groups were performed with 1-way analysis of variance with Student-Newman-Keuls correction for multiple comparisons and with Kruskal-Wallis test where appropriate. The Spearman rank coefficient was used to assess the correlation between maternal and fetal hemodynamics. Pregnancies were observed until delivery. RESULTS: A total of 182 normotensive pregnancies were included. After the evaluation, 54 fetuses were classified as growth restricted, 42 as small for gestational age, and 86 as adequate for gestational age. The fetus with fetal growth restriction had significantly lower umbilical vein diameter (P<.0001), umbilical vein velocity (P=.02), umbilical vein flow (P<.0001), and umbilical vein flow corrected for fetal weight (P<.01) than adequate-for-gestational-age and small-for-gestational-age fetuses. The maternal hemodynamic profile in fetal growth restriction was characterized by elevated systemic vascular resistance and reduced cardiac output. The umbilical vein diameter was positively correlated to maternal cardiac output (rs=0.261), whereas there was a negative correlation between maternal systemic vascular resistance (rs=-0.338) and maternal potential energy-to-kinetic energy ratio (rs=-0267). The fetal umbilical vein time averaged max velocity was positively correlated to maternal cardiac output (rs=0.189) and maternal inotr

Journal article

Mullins E, Perry A, Banerjee J, Townson J, Grozeva D, Milton R, Kirby N, Playle R, Bourne T, Lees C, PAN-COVID Investigatorset al., 2022, Pregnancy and neonatal outcomes of COVID-19: The PAN-COVID study., European Journal of Obstetrics Gynecology and Reproductive Biology, Vol: 276, Pages: 161-167, ISSN: 0301-2115

OBJECTIVE: To assess perinatal outcomes for pregnancies affected by suspected or confirmed SARS-CoV-2 infection. METHODS: Prospective, web-based registry. Pregnant women were invited to participate if they had suspected or confirmed SARS-CoV-2 infection between 1st January 2020 and 31st March 2021 to assess the impact of infection on maternal and perinatal outcomes including miscarriage, stillbirth, fetal growth restriction, pre-term birth and transmission to the infant. RESULTS: Between April 2020 and March 2021, the study recruited 8239 participants who had suspected or confirmed SARs-CoV-2 infection episodes in pregnancy between January 2020 and March 2021. Maternal death affected 14/8197 (0.2%) participants, 176/8187 (2.2%) of participants required ventilatory support. Pre-eclampsia affected 389/8189 (4.8%) participants, eclampsia was reported in 40/ 8024 (0.5%) of all participants. Stillbirth affected 35/8187 (0.4 %) participants. In participants delivering within 2 weeks of delivery 21/2686 (0.8 %) were affected by stillbirth compared with 8/4596 (0.2 %) delivering ≥ 2 weeks after infection (95 % CI 0.3-1.0). SGA affected 744/7696 (9.3 %) of livebirths, FGR affected 360/8175 (4.4 %) of all pregnancies. Pre-term birth occurred in 922/8066 (11.5%), the majority of these were indicated pre-term births, 220/7987 (2.8%) participants experienced spontaneous pre-term births. Early neonatal deaths affected 11/8050 livebirths. Of all neonates, 80/7993 (1.0%) tested positive for SARS-CoV-2. CONCLUSIONS: Infection was associated with indicated pre-term birth, most commonly for fetal compromise. The overall proportions of women affected by SGA and FGR were not higher than expected, however there was the proportion affected by stillbirth in participants delivering within 2 weeks of infection was significantly higher than those delivering ≥ 2 weeks after infection. We suggest that clinicians' thresh

Journal article

Khalil A, Samara A, O'Brien P, Morris E, Draycott T, Lees C, Ladhani Set al., 2022, Monkeypox and pregnancy: what do obstetricians need to know?, ULTRASOUND IN OBSTETRICS & GYNECOLOGY, Vol: 60, Pages: 22-27, ISSN: 0960-7692

Journal article

Masini G, Foo LF, Tay J, Wilkinson IB, Valensise H, Gyselaers W, Lees CCet al., 2022, Reply: Preeclampsia has 2 phenotypes that require different treatment strategies, AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY, Vol: 227, Pages: 114-115, ISSN: 0002-9378

Journal article

Matsuzaki S, Youssefzadeh AC, Matsuo K, Wilkinson IB, Valensise H, Gyselaers W, Lees CCet al., 2022, Optimizing the strategy of antenatal corticosteroids in threatened preterm labor, AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY, Vol: 227, Pages: 116-+, ISSN: 0002-9378

Journal article

Zielinska A, Mullins E, Lees C, 2022, The feasibility of multi-modality remote monitoring of maternal physiology during pregnancy, Medicine, Vol: 101, ISSN: 0025-7974

Objectives: Gestational hypertension affects 10% of pregnancies, may occur without warning and has wide ranging effects on maternal, fetal and infant health. Antenatal care largely relies on in-person appointments, hence only <4% of the pregnancy period is subject to routine clinical monitoring. Home monitoring offers a unique opportunity to collect granular data and identify trends in maternal physiology that could predict pregnancy compromise. Our objective was to investigate the feasibility of remote multi-domain monitoring of maternal cardiovascular health both in and after pregnancy. Methods: Prospective feasibility study of continuous remote monitoring of multiple modalities indicative of cardiovascular health from the first trimester to six weeks post-partum.Results: Twenty-four pregnant women were asked to monitor body weight, heart rate, blood pressure, activity levels and sleep patterns daily. Study participants took on average 4.3 (SD= 2.20) home recordings of each modality per week across the three trimesters and 2.0 post-partum (SD= 2.41), out of a recommended maximum of 7. Participant retention was 58.3%. Wearing a smartwatch daily was reported as feasible (8.6/10, SD= 2.3) and data could be entered digitally with ease (7.7/10, SD= 2.4). Conclusion: Remote digital monitoring of cardiovascular health is feasible for research purposes and hence potentially so for routine clinical care throughout and after pregnancy. 58% of women completed the study. Multiple modalities indicative of cardiovascular health can be measured in parallel, giving a global view that is representative of the whole pregnancy period in a way that current antenatal care is not.

Journal article

Stampalija T, Wolf H, Mylrea-Foley B, Marlow N, Stephens KJ, Shaw CJ, Lees CC, TRUFFLE-2 Feasibility Study authorset al., 2022, Reduced fetal growth velocity and weight loss are associated with adverse perinatal outcome in fetuses at risk of growth restriction., Am J Obstet Gynecol

BACKGROUND: Although fetal size is associated with adverse perinatal outcome, the relationship between fetal growth velocity and adverse perinatal outcome is unclear. OBJECTIVE: This study aimed to evaluate the relationship between fetal growth velocity and signs of cerebral blood flow redistribution, and their association with birthweight and adverse perinatal outcome. STUDY DESIGN: This study was a secondary analysis of the TRUFFLE-2 multicenter observational prospective feasibility study of fetuses at risk of fetal growth restriction between 32+0 and 36+6 weeks of gestation (n=856), evaluated by ultrasound biometry and umbilical and middle cerebral artery Doppler. Individual fetal growth velocity was calculated from the difference of birthweight and estimated fetal weight at 3, 2, and 1 week before delivery, and by linear regression of all available estimated fetal weight measurements. Fetal estimated weight and birthweight were expressed as absolute value and as multiple of the median for statistical calculation. The coefficients of the individual linear regression of estimated fetal weight measurements (growth velocity; g/wk) were plotted against the last umbilical-cerebral ratio with subclassification for perinatal outcome. The association of these measurements with adverse perinatal outcome was assessed. The adverse perinatal outcome was a composite of abnormal condition at birth or major neonatal morbidity. RESULTS: Adverse perinatal outcome was more frequent among fetuses whose antenatal growth was <100 g/wk, irrespective of signs of cerebral blood flow redistribution. Infants with birthweight <0.65 multiple of the median were enrolled earlier, had the lowest fetal growth velocity, higher umbilical-cerebral ratio, and were more likely to have adverse perinatal outcome. A decreasing fetal growth velocity was observed in 163 (19%) women in whom the estimated fetal weight multiple of the median regression coefficient was <-0.025, and who had higher um

Journal article

Vieira MC, Relph S, Muruet-Gutierrez W, Elstad M, Coker B, Moitt N, Delaney L, Winsloe C, Healey A, Coxon K, Alagna A, Briley A, Johnson M, Page LM, Peebles D, Shennan A, Thilaganathan B, Marlow N, McCowan L, Lees C, Lawlor DA, Khalil A, Sandall J, Copas A, Pasupathy D, DESiGN Collaborative Groupet al., 2022, Evaluation of the Growth Assessment Protocol (GAP) for antenatal detection of small for gestational age: The DESiGN cluster randomised trial, PLoS Medicine, Vol: 19, ISSN: 1549-1277

BACKGROUND: Antenatal detection and management of small for gestational age (SGA) is a strategy to reduce stillbirth. Large observational studies provide conflicting results on the effect of the Growth Assessment Protocol (GAP) in relation to detection of SGA and reduction of stillbirth; to the best of our knowledge, there are no reported randomised control trials. Our aim was to determine if GAP improves antenatal detection of SGA compared to standard care. METHODS AND FINDINGS: This was a pragmatic, superiority, 2-arm, parallel group, open, cluster randomised control trial. Maternity units in England were eligible to participate in the study, except if they had already implemented GAP. All women who gave birth in participating clusters (maternity units) during the year prior to randomisation and during the trial (November 2016 to February 2019) were included. Multiple pregnancies, fetal abnormalities or births before 24+1 weeks were excluded. Clusters were randomised to immediate implementation of GAP, an antenatal care package aimed at improving detection of SGA as a means to reduce the rate of stillbirth, or to standard care. Randomisation by random permutation was stratified by time of study inclusion and cluster size. Data were obtained from hospital electronic records for 12 months prerandomisation, the washout period (interval between randomisation and data collection of outcomes), and the outcome period (last 6 months of the study). The primary outcome was ultrasound detection of SGA (estimated fetal weight <10th centile using customised centiles (intervention) or Hadlock centiles (standard care)) confirmed at birth (birthweight <10th centile by both customised and population centiles). Secondary outcomes were maternal and neonatal outcomes, including induction of labour, gestational age at delivery, mode of birth, neonatal morbidity, and stillbirth/perinatal mortality. A 2-stage cluster-summary statistical approach calculated the absolute difference

Journal article

Smith ER, Oakley E, He S, Zavala R, Ferguson K, Miller L, Grandner GW, Abejirinde I-OO, Afshar Y, Ahmadzia H, Aldrovandi G, Akelo V, Tippett Barr BA, Bevilacqua E, Brandt JS, Broutet N, Fernández Buhigas I, Carrillo J, Clifton R, Conry J, Cosmi E, Delgado-López C, Divakar H, Driscoll AJ, Favre G, Flaherman V, Gale C, Gil MM, Godwin C, Gottlieb S, Hernandez Bellolio O, Kara E, Khagayi S, Kim CR, Knight M, Kotloff K, Lanzone A, Le Doare K, Lees C, Litman E, Lokken EM, Laurita Longo V, Magee LA, Martinez-Portilla RJ, McClure E, Metz TD, Money D, Mullins E, Nachega JB, Panchaud A, Playle R, Poon LC, Raiten D, Regan L, Rukundo G, Sanin-Blair J, Temmerman M, Thorson A, Thwin S, Tolosa JE, Townson J, Valencia-Prado M, Visentin S, von Dadelszen P, Adams Waldorf K, Whitehead C, Yang H, Thorlund K, Tielsch JMet al., 2022, Protocol for a sequential, prospective meta-analysis to describe coronavirus disease 2019 (COVID-19) in the pregnancy and postpartum periods, PLoS One, Vol: 17, ISSN: 1932-6203

We urgently need answers to basic epidemiological questions regarding SARS-CoV-2 infection in pregnant and postpartum women and its effect on their newborns. While many national registries, health facilities, and research groups are collecting relevant data, we need a collaborative and methodologically rigorous approach to better combine these data and address knowledge gaps, especially those related to rare outcomes. We propose that using a sequential, prospective meta-analysis (PMA) is the best approach to generate data for policy- and practice-oriented guidelines. As the pandemic evolves, additional studies identified retrospectively by the steering committee or through living systematic reviews will be invited to participate in this PMA. Investigators can contribute to the PMA by either submitting individual patient data or running standardized code to generate aggregate data estimates. For the primary analysis, we will pool data using two-stage meta-analysis methods. The meta-analyses will be updated as additional data accrue in each contributing study and as additional studies meet study-specific time or data accrual thresholds for sharing. At the time of publication, investigators of 25 studies, including more than 76,000 pregnancies, in 41 countries had agreed to share data for this analysis. Among the included studies, 12 have a contemporaneous comparison group of pregnancies without COVID-19, and four studies include a comparison group of non-pregnant women of reproductive age with COVID-19. Protocols and updates will be maintained publicly. Results will be shared with key stakeholders, including the World Health Organization (WHO) Maternal, Newborn, Child, and Adolescent Health (MNCAH) Research Working Group. Data contributors will share results with local stakeholders. Scientific publications will be published in open-access journals on an ongoing basis.

Journal article

Gyselaers W, Lees C, 2022, Maternal Low Volume Circulation Relates to Normotensive and Preeclamptic Fetal Growth Restriction, FRONTIERS IN MEDICINE, Vol: 9

Journal article

Rizzo G, Ghi T, Henrich W, Tutschek B, Kamel RAM, Lees CC, Mappa I, Kovalenko M, Lau W, Eggebo T, Achiron R, Sen Cet al., 2022, Ultrasound in labor: clinical practice guideline and recommendation by the WAPM-World Association of Perinatal Medicine and the PMF-Perinatal Medicine Foundation, JOURNAL OF PERINATAL MEDICINE, Vol: 50, Pages: 1007-1029, ISSN: 0300-5577

Journal article

Mylrea-Foley B, Thornton JG, Mullins E, Marlow N, Hecher K, Ammari C, Arabin B, Berger A, Bergman E, Bhide A, Bilardo C, Binder J, Breeze A, Brodszki J, Calda P, Cannings-John R, Cerny A, Cesari E, Cetin I, Dall'Asta A, Diemert A, Ebbing C, Eggebo T, Fantasia I, Ferrazzi E, Frusca T, Ghi T, Goodier J, Greimel P, Gyselaers W, Hassan W, Von Kaisenberg C, Kholin A, Klaritsch P, Krofta L, Lindgren P, Lobmaier S, Marsal K, Maruotti GM, Mecacci F, Myklestad K, Napolitano R, Ostermayer E, Papageorghiou A, Potter C, Prefumo F, Raio L, Richter J, Sande RK, Schlembach D, Schleussner E, Stampalija T, Thilaganathan B, Townson J, Valensise H, Ha Visser G, Wee L, Wolf H, Lees CCet al., 2022, Perinatal and 2-year neurodevelopmental outcome in late preterm fetal compromise: the TRUFFLE 2 randomised trial protocol, BMJ Open, Vol: 12, Pages: 1-8, ISSN: 2044-6055

Introduction Following the detection of fetal growth restriction, there is no consensus about the criteria that should trigger delivery in the late preterm period. The consequences of inappropriate early or late delivery are potentially important yet practice varies widely around the world, with abnormal findings from fetal heart rate monitoring invariably leading to delivery. Indices derived from fetal cerebral Doppler examination may guide such decisions although there are few studies in this area. We propose a randomised, controlled trial to establish the optimum method of timing delivery between 32 weeks and 36 weeks 6 days of gestation. We hypothesise that delivery on evidence of cerebral blood flow redistribution reduces a composite of perinatal poor outcome, death and short-term hypoxia-related morbidity, with no worsening of neurodevelopmental outcome at 2 years.Methods and analysis Women with non-anomalous singleton pregnancies 32+0 to 36+6 weeks of gestation in whom the estimated fetal weight or abdominal circumference is <10th percentile or has decreased by 50 percentiles since 18–32 weeks will be included for observational data collection. Participants will be randomised if cerebral blood flow redistribution is identified, based on umbilical to middle cerebral artery pulsatility index ratio values. Computerised cardiotocography (cCTG) must show normal fetal heart rate short term variation (≥4.5 msec) and absence of decelerations at randomisation. Randomisation will be 1:1 to immediate delivery or delayed delivery (based on cCTG abnormalities or other worsening fetal condition). The primary outcome is poor condition at birth and/or fetal or neonatal death and/or major neonatal morbidity, the secondary non-inferiority outcome is 2-year infant general health and neurodevelopmental outcome based on the Parent Report of Children’s Abilities-Revised questionnaire.Ethics and dissemination The Study Coordination Centre has obtaine

Journal article

Lees CC, Romero R, Stampalija T, Dall'Asta A, DeVore GA, Prefumo F, Frusca T, Visser GHA, Hobbins JC, Baschat AA, Bilardo CM, Galan HL, Campbell S, Maulik D, Figueras F, Lee W, Unterscheider J, Valensise H, Da Silva Costa F, Salomon LJ, Poon LC, Ferrazzi E, Mari G, Rizzo G, Kingdom JC, Kiserud T, Hecher Ket al., 2022, Clinical Opinion: The diagnosis and management of suspected fetal growth restriction: an evidence-based approach, American Journal of Obstetrics and Gynecology, Vol: 226, Pages: 366-378, ISSN: 0002-9378

This study reviewed the literature about the diagnosis, antepartum surveillance, and time of delivery of fetuses suspected to be small for gestational age or growth restricted. Several guidelines have been issued by major professional organizations, including the International Society of Ultrasound in Obstetrics and Gynecology and the Society for Maternal-Fetal Medicine. The differences in recommendations, in particular about Doppler velocimetry of the ductus venosus and middle cerebral artery, have created confusion among clinicians, and this review has intended to clarify and highlight the available evidence that is pertinent to clinical management. A fetus who is small for gestational age is frequently defined as one with an estimated fetal weight of <10th percentile. This condition has been considered syndromic and has been frequently attributed to fetal growth restriction, a constitutionally small fetus, congenital infections, chromosomal abnormalities, or genetic conditions. Small for gestational age is not synonymous with fetal growth restriction, which is defined by deceleration of fetal growth determined by a change in fetal growth velocity. An abnormal umbilical artery Doppler pulsatility index reflects an increased impedance to flow in the umbilical circulation and is considered to be an indicator of placental disease. The combined finding of an estimated fetal weight of <10th percentile and abnormal umbilical artery Doppler velocimetry has been widely accepted as indicative of fetal growth restriction. Clinical studies have shown that the gestational age at diagnosis can be used to subclassify suspected fetal growth restriction into early and late, depending on whether the condition is diagnosed before or after 32 weeks of gestation. The early type is associated with umbilical artery Doppler abnormalities, whereas the late type is often associated with a low pulsatility index in the middle cerebral artery. A large randomized clinical trial indicate

Journal article

Srinivasan D, Shaw CJ, Dall'Asta A, Papanikoloau K, Yazbek J, Lees CCet al., 2022, Expert opinion: Stepwise ultrasound assessment of suspected placenta accreta spectrum using 2D, Doppler and 3D imaging, EUROPEAN JOURNAL OF OBSTETRICS & GYNECOLOGY AND REPRODUCTIVE BIOLOGY, Vol: 270, Pages: 181-189, ISSN: 0301-2115

Journal article

Salvesen K, Ter Haar G, Miloro P, Sinkovskaya E, Lees C, Bourne T, Maršál K, Dall'asta A, Bioeffects and Safety Committee and the Board of the International Society of Ultrasound in Obstetrics and Gynecology ISUOGet al., 2022, ISUOG Safety Committee updated recommendation on use of respirators by practitioners undertaking obstetric and gynecological ultrasound in context of SARS-CoV-2 Omicron variant of concern, Ultrasound in Obstetrics and Gynecology, Vol: 59, Pages: 411-411, ISSN: 0960-7692

Journal article

Bourne T, Kyriacou C, Shah H, Ceusters J, Preisler J, Metzger U, Landolfo C, Lees C, Timmerman Det al., 2022, The experiences and wellbeing of healthcare professionals working in the field of ultrasound in Obstetrics and Gynecology as the SARS-CoV-2 pandemic was evolving: a cross-sectional survey study, BMJ Open, Vol: 12, Pages: 1-12, ISSN: 2044-6055

Objectives: Assess experience of healthcare professionals (HCPs) working with ultrasound in Obstetrics and Gynecology during the evolving SARS-CoV-2 pandemic given the new and unprecedented challenges involving viral exposure, personal protective equipment (PPE) and wellbeing.Design: Prospective cross-sectional survey study.Setting: Online international survey. Single-best, open box and Hospital and Anxiety Depression Scale (HADS) questions.Participants: The survey was sent to 35,509 HCPs in 124 countries and was open from 7th-21st May 2020. 2237/3237 (69.1%) HCPs from 115 countries who consented to participate completed the survey. 1058 (47.3%) completed the HADS. Primary outcome measures: Overall prevalence of SARS-CoV-2, depression and anxiety amongst HCPs in relation to country and PPE availability.Analyses: Univariate analyses were used to investigate associations without generating erroneous causal conclusions.Results: Confirmed/suspected SARS-CoV-2 prevalence was 13.0%. PPE provision concerns were raised by 74.1% of participants; highest amongst trainees/resident physicians (83.9%), and amongst HCPs in Spain (89.7%). Most participants worked in self-perceived high-risk areas for SARS-CoV-2 (67.5-87.0%), with proportionately more trainees interacting with suspected/confirmed infected patients (57.1% versus 24.2-40.6%) and sonographers seeing more patients who did not wear a mask (33.3% versus 13.9-7.9%). The most frequent PPE combination used were gloves and a surgical mask (22.3%). UK and US respondents reported spending less time self-isolating (8.8 days) and lower satisfaction with their national pandemic response (37.0-43.0%). 19.8% and 8.8% of respondents met the criteria for moderate to severe anxiety and depression respectively. Conclusions: Reported SARS-CoV-2 HCP prevalence is consistent with literature findings. Most respondents used gloves and a surgical mask, with a greater SARS-CoV-2 prevalence compared with those using ‘full’ PPE. HCP

Journal article

Masini G, Foo LF, Tay J, Wilkinson IB, Valensise H, Gyselaers W, Lees CCet al., 2022, Preeclampsia has two phenotypes which require different treatment strategies, American Journal of Obstetrics and Gynecology, Vol: 226, Pages: S1006-S1018, ISSN: 0002-9378

The opinion on the mechanisms underlying the pathogenesis of preeclampsia still divides scientists and clinicians. This common complication of pregnancy has long been viewed as a disorder linked primarily to placental dysfunction, which is caused by abnormal trophoblast invasion, however, evidence from the previous two decades has triggered and supported a major shift in viewing preeclampsia as a condition that is caused by inherent maternal cardiovascular dysfunction, perhaps entirely independent of the placenta. In fact, abnormalities in the arterial and cardiac functions are evident from the early subclinical stages of preeclampsia and even before conception. Moving away from simply observing the peripheral blood pressure changes, studies on the central hemodynamics reveal two different mechanisms of cardiovascular dysfunction thought to be reflective of the early-onset and late-onset phenotypes of preeclampsia. More recent evidence identified that the underlying cardiovascular dysfunction in these phenotypes can be categorized according to the presence of coexisting fetal growth restriction instead of according to the gestational period at onset, the former being far more common at early gestational ages. The purpose of this review is to summarize the hemodynamic research observations for the two phenotypes of preeclampsia. We delineate the physiological hemodynamic changes that occur in normal pregnancy and those that are observed with the pathologic processes associated with preeclampsia. From this, we propose how the two phenotypes of preeclampsia could be managed to mitigate or redress the hemodynamic dysfunction, and we consider the implications for future research based on the current evidence. Maternal hemodynamic modifications throughout pregnancy can be recorded with simple-to-use, noninvasive devices in obstetrical settings, which require only basic training. This review includes a brief overview of the methodologies and techniques used to study hemody

Journal article

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