Publications by authors named "Christoph Lees"

128 Publications

Pregnancy and neonatal outcomes of COVID-19: co-reporting of common outcomes from PAN-COVID and AAP SONPM registries.

Ultrasound Obstet Gynecol 2021 Feb 23. Epub 2021 Feb 23.

Institute of Reproductive and Developmental Biology, Imperial College London, Centre for Fetal Care Imperial College Healthcare NHS Trust.

Objective: Few large cohort studies have reported data on maternal, fetal, perinatal and neonatal outcomes associated with SARS-CoV-2 infection in pregnancy. We report the outcome of infected pregnancies from a collaboration formed early during the pandemic between the investigators of two registries, the UK and global Pregnancy and Neonatal outcomes in COVID-19 (PAN-COVID) study and the US American Academy of Pediatrics Section on Neonatal Perinatal Medicine (AAP SONPM) National Perinatal COVID-19 Registry.

Methods: This was an analysis of data from the PAN-COVID registry (January 1 to July 25 2020), which includes pregnancies with suspected or confirmed maternal SARS-CoV-2 infection at any stage in pregnancy, and the AAP SONPM National Perinatal COVID-19 registry (April 4 to August 8 2020), which includes pregnancies with positive maternal testing for SARS-CoV-2 from 14 days before delivery to 3 days after delivery. The registries collected data on maternal, fetal, perinatal and neonatal outcomes. The PAN-COVID results are presented both overall for pregnancies with suspected or confirmed SARS-CoV-2 infection and separately in those with confirmed infection.

Results: We report on 4005 pregnant women with suspected or confirmed SARS-CoV-2 infection (1606 from PAN-COVID and 2399 from AAP SONPM). For obstetric outcomes, in PAN-COVID overall, those with confirmed infection in PAN-COVID and AAP SONPM, respectively, maternal death occurred in 0.5%, 0.5% and 0.2% of cases, early neonatal death in 0.2%, 0.3% and 0.3% of cases and stillbirth in 0.5%, 0.6% and 0.4% of cases. Delivery was pre-term (<37 weeks' gestation) in 12.0% of all women in PAN-COVID, in 16.2% of those women with confirmed infection in PAN-COVID and in 15.7% of women in AAP SONPM. Extremely preterm delivery (< 27 weeks' gestation) occurred in 0.5% of cases in PAN-COVID and 0.3% in AAP SONPM. Neonatal SARS-CoV-2 infection was reported in 0.8% of all deliveries in PAN-COVID, in 2.0% in those with confirmed infection in PAN-COVID and in 1.8% in AAP SONPM; the proportions of neonates tested were 9.5%, 20.7% and 87.2%, respectively. The rates of a SGA neonate were 8.2% in PAN-COVID overall, 9.7% in those with confirmed infection and 9.6% in AAP SONPM. Mean gestational age adjusted birth-weight z-scores were -0.03 in PAN-COVID and -0.18 in AAP SONPM.

Conclusions: The findings from the UK and US registries of pregnancies with SARS-CoV-2 infection were remarkably concordant. Preterm delivery affected a higher proportion of women than expected based on historical and contemporaneous national data. The proportions of pregnancies affected by stillbirth, a small for gestational age infant or early neonatal death were comparable to those in historical and contemporaneous UK and US data. Although maternal death was uncommon, the rate was higher than expected based on UK and US population data, which is likely explained by under-ascertainment of women affected by milder or asymptomatic infection in pregnancy in the PAN-COVID study although not in the AAP SONPM study. The data presented support strong guidance for enhanced precautions to prevent SARS-CoV-2 infection in pregnancy, particularly in the context of increased risks of preterm delivery and maternal mortality, and for priority vaccination of women planning pregnancy. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/uog.23619DOI Listing
February 2021

Evaluation of the Tramline Sign in the Prediction of Placenta Accreta Spectrum and Perioperative Outcomes in Anterior Placenta Previa.

Ultraschall Med 2021 Feb 8. Epub 2021 Feb 8.

Queen Charlottes and Chelsea Hospital, Imperial College Hleathcare NHS Trust, London, United Kingdom.

Purpose:  To evaluate perioperative outcomes and the prognostic role of the tramline sign in a cohort of women with anterior placenta previa.

Materials And Methods:  Retrospective analysis of 3D ultrasound volumes from women with anterior placenta previa who underwent ultrasound examination beyond 32 weeks. 3D and 3D color volumes were obtained from a sagittal section of the uterus bisecting a partially full bladder and processed using Crystal Vue and Crystal Vue Flow rendering to look for the "tramline sign". "Partial obliteration" was defined as a loss of some or part of the uterine-serosal interface and "full obliteration" as when both interfaces were interrupted. Postnatal ascertainment of placenta accreta spectrum (PAS) was confirmed by findings recorded intraoperatively or on a pathology report.

Results:  65 cases were included. The tramline sign was "partially" (17) or "fully" (19) obliterated in 36 cases (55.4 %), and present in 29 (44.6 %). Obliteration was associated with earlier gestational age at delivery (35 + 1 (26 + 3-38 + 3) vs. 36 + 4 (25 + 3-38 + 0) weeks, p = 0.005), greater estimated blood loss (800 (400-11 000) vs. 600 (300-2100) mls, p = 0.003), longer operative time (155 (60-240) vs. 54 (25-80) minutes, p < 0.001), higher rate of hysterectomy (97.2 % vs. 0.0 %, p < 0.001), longer postoperative admission (7 (3-19) vs. 3 (1-5) days, p < 0.001) and a 100 % rate of postnatal diagnosis of PAS. The finding of an "obliterated" tramline sign identified all women that required hysterectomy and all cases of PAS.

Conclusion:  A "partially or fully obliterated" tramline sign is strongly associated with indicators of operative complexity, the postnatal confirmation of PAS, and the need for peripartum hysterectomy.
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http://dx.doi.org/10.1055/a-1309-1665DOI Listing
February 2021

Pregnancy and neonatal outcomes in COVID-19: study protocol for a global registry of women with suspected or confirmed SARS-CoV-2 infection in pregnancy and their neonates, understanding natural history to guide treatment and prevention.

BMJ Open 2021 01 29;11(1):e041247. Epub 2021 Jan 29.

Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, UK

Introduction: Previous novel COVID-19 pandemics, SARS and middle east respiratory syndrome observed an association of infection in pregnancy with preterm delivery, stillbirth and increased maternal mortality. COVID-19, caused by SARS-CoV-2 infection, is the largest pandemic in living memory.Rapid accrual of robust case data on women in pregnancy and their babies affected by suspected COVID-19 or confirmed SARS-CoV-2 infection will inform clinical management and preventative strategies in the current pandemic and future outbreaks.

Methods And Analysis: The pregnancy and neonatal outcomes in COVID-19 (PAN-COVID) registry are an observational study collecting focused data on outcomes of pregnant mothers who have had suspected COVID-19 in pregnancy or confirmed SARS-CoV-2 infection and their neonates via a web-portal. Among the women recruited to the PAN-COVID registry, the study will evaluate the incidence of: (1) miscarriage and pregnancy loss, (2) fetal growth restriction and stillbirth, (3) preterm delivery, (4) vertical transmission (suspected or confirmed) and early onset neonatal SARS-CoV-2 infection.Data will be centre based and collected on individual women and their babies. Verbal consent will be obtained, to reduce face-to-face contact in the pandemic while allowing identifiable data collection for linkage. Statistical analysis of the data will be carried out on a pseudonymised data set by the study statistician. Regular reports will be distributed to collaborators on the study research questions.

Ethics And Dissemination: This study has received research ethics approval in the UK. For international centres, evidence of appropriate local approval will be required to participate, prior to entry of data to the database. The reports will be published regularly. The outputs of the study will be regularly disseminated to participants and collaborators on the study website (https://pan-covid.org) and social media channels as well as dissemination to scientific meetings and journals.

Study Registration Number: ISRCTN68026880.
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http://dx.doi.org/10.1136/bmjopen-2020-041247DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7849873PMC
January 2021

Fetal weight change close to term is proportional to the birthweight percentile.

Eur J Obstet Gynecol Reprod Biol 2021 Feb 13;257:84-87. Epub 2020 Dec 13.

Queen Charlotte's & Chelsea Hospital, Du Cane Road, London W12 0HS, United Kingdom; Department of Obstetrics & Gynaecology, KU Leuven, 3000 Leuven, Belgium. Electronic address:

Objective: To investigate the relationship between the difference in estimated fetal weight and birthweight at or close to term, and in relation to Doppler parameters.

Study Design: A cohort study of all term singleton pregnancies who underwent an ultrasound within two weeks of delivery after 36 weeks at one institution in one calendar year. When available, Doppler measurements of umbilical and middle cerebral artery pulsatility index were recorded. Data were analysed by Pearson rank correlation.

Results: Of 8517 eligible deliveries, 885 women had an ultrasound scan within 2 weeks of delivery. Mean daily differences between estimated fetal weight and birth weight were: those born <10th percentile lost 26 g per day (95 % CI -36 to -16), 10-50th percentile gained 7 g per day (95 % CI -2 to 15), 50th-90th percentile gained 27 g per day (95 % CI 19-35) and >90th percentile gained 48 g per day (95 % CI 32-64). There was a negative correlation between umbilical: middle cerebral artery pulsatility index and the change in weight per day (n = 348, p = 0.001, r = 0.17).

Conclusions: Difference in the estimated fetal weight and birthweight, expressed as grams growth per day, is proportional to the birthweight percentile. Fetuses with a birthweight >10th percentile gain weight, while those with a birthweight <10th percentile apparently decline in weight between their final ultrasound estimated fetal weight and delivery. In babies with the smallest or apparent negative weight gain there was an association with Doppler parameters that signified hypoxia indicating fetal growth at term may be restricted by impaired placental function. Estimated fetal weight may be a poor predictor of birthweight for reasons other than ultrasound or algorithmic error.
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http://dx.doi.org/10.1016/j.ejogrb.2020.12.023DOI Listing
February 2021

Uterine Transplantation; Review of Livebirths and Reproductive Implications.

Transplantation 2020 Dec 10. Epub 2020 Dec 10.

Hammersmith Hospital, Imperial College NHS Trust, W12 0HS London, UK.

Uterine transplantation (UTx) is a fertility restoring treatment for women with absolute uterine factor infertility. At a time when there is no question of the procedure's feasibility, and as the number of livebirths begins to increase exponentially, various important reproductive, fetal and maternal medicine implications have emerged. Detailed outcomes from 17 livebirths following UTx are now available, which are reviewed herein, along with contextualized extrapolation from pregnancy outcomes in other solid organ transplants. Differences in recipient demographics and reproductive aspirations between UTx and other transplant recipients make extrapolating management strategies and outcomes in other solid organ transplants inappropriate. Whereas preterm delivery remains prominent, small for gestational age or hypertensive disorders do not appear to be as prevalent following UTx when compared to other solid organ transplants. Given the primary objective of undertaking UTx is to achieve a livebirth, publication of reproductive outcomes is essential at this early stage, to reflect upon and optimize the management of future cases.
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http://dx.doi.org/10.1097/TP.0000000000003578DOI Listing
December 2020

Maternal Cardiovascular Dysfunction is Associated with Hypoxic Cerebral and Umbilical Doppler Changes.

J Clin Med 2020 Sep 7;9(9). Epub 2020 Sep 7.

Centre for Fetal Care, Queen Charlotte's and Chelsea Hospital, Imperial College Healthcare NHS Trust, London W12 0HS, UK.

We investigate the relationship between maternal cardiovascular (CV) function and fetal Doppler changes in healthy pregnancies and those with pre-eclampsia (PE), small for gestational age (SGA) or fetal growth restriction (FGR). This was a three-centre prospective study, where CV assessment was performed using inert gas rebreathing, continuous Doppler or impedance cardiography. Maternal cardiac output (CO) and peripheral vascular resistance (PVR) were analysed in relation to the uterine artery, umbilical artery (UA) and middle cerebral artery (MCA) pulsatility indices (PI, expressed as -scores by gestational week) using polynomial regression analyses, and in relation to the presence of absent/reversed end diastolic (ARED) flow in the UA. We included 81 healthy controls, 47 women with PE, 65 with SGA/FGR and 40 with PE + SGA/FGR. Maternal CO was inversely related to fetal UA PI and positively related to MCA PI; the opposite was observed for PVR, which was also positively associated with increased uterine artery impedance. CO was lower (-score 97, = 0.02) and PVR higher (-score 2.88, = 0.02) with UA ARED flow. We report that maternal CV dysfunction is associated with fetal vascular changes, namely raised impedance in the fetal-placental circulation and low impedance in the fetal cerebral vessels. These findings are most evident with critical UA Doppler changes and represent a potential mechanism for therapeutic intervention.
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http://dx.doi.org/10.3390/jcm9092891DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7565559PMC
September 2020

Maternal and fetal cardiovascular and metabolic effects of intra-operative uterine handling under general anesthesia during pregnancy in sheep.

Sci Rep 2020 07 2;10(1):10867. Epub 2020 Jul 2.

Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, CB2 3EG, UK.

A cohort study of 6,500,000 human pregnancies showed an increased risk of adverse fetal outcomes following abdominal but not non-abdominal surgery under general anesthesia. This may be the consequence of uterine handling during abdominal surgery. However, there are no data on any effects on the cardiometabolic physiology of the fetus or mother in response to uterine manipulation in otherwise healthy pregnancy. Consequently, 9 sheep in late gestation were anesthetized with isofluorane and maternal and fetal catheters and flow probes were implanted to determine cardiovascular and metabolic changes during uterine handling. Uterine handling led to an acute increase in uterine artery vascular resistance, fetal peripheral vasoconstriction, a reduction in oxygen delivery to the femoral circulation, worsening fetal acidosis. There was no evidence of systemic fetal hypoxia, or changes in fetal heart rate, carotid blood flow or carotid oxygen delivery. Therefore, the data support that uterine handling during abdominal surgery under general anesthesia can impact adversely on fetal cardiometabolic health. This may provide a potential explanation linking adverse fetal outcomes in abdominal compared with non-abdominal surgery during pregnancy. The data have important implications for human fetal surgery where the uterus is handled, as operative procedures during late gestation under general maternal anesthesia become more prevalent.
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http://dx.doi.org/10.1038/s41598-020-67714-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7331497PMC
July 2020

Evaluation of perioperative complications using a newly described staging system for placenta accreta spectrum.

Eur J Obstet Gynecol Reprod Biol 2020 Jul 21;250:54-60. Epub 2020 Apr 21.

Centre for Fetal Care, Queen Charlotte's and Chelsea Hospital, Imperial College Healthcare NHS Trust, London, United Kingdom; Department of Metabolism, Digestion and Reproduction, Institute of Reproductive and Developmental Biology, Imperial College London, United Kingdom; Department of Development and Regeneration, KU Leuven, Belgium. Electronic address:

Introduction: The antenatal diagnosis of placenta accreta spectrum (PAS) is in large part subjective and based on expert interpretation. The aim of this study was to externally evaluate a recently developed staging system based on specific and defined prenatal ultrasound (US) features in a cohort of women at risk of PAS undergoing specialist prenatal US, in particular relating to surgical morbidity at delivery.

Materials And Methods: Database study of cases with confirmed placenta previa. In all, the placenta was evaluated in a systematic fashion. PAS was subclassified in PAS0-PAS3 according to the loss of clear zone, placental lacunae, bladder wall interruption, uterovesical hypervascularity and increased vascularity in the parametrial region.

Results: 43 cases were included, of whom 33 had major placenta previa. 31 cases were categorized as PAS0; 3, 4 and 5 cases as PAS1, PAS2 and PAS3, respectively. All women underwent caesarean section and hysterectomy was required in 10. The comparison of the perinatal outcomes among the PAS categories yielded greater operative time (50 (35-129) minutes for PAS0 vs 70 (48-120) for PAS1 vs 95 (60-150) for PAS2 vs 100 (87-180) for PAS3, p < 0.001) and estimated blood loss (800 (500-2500) mls for PAS0 vs 3500 (800-7500) for PAS1 vs 2850 (500-7500) for PAS2 vs 6000 (2500-11000) for PAS3, p < 0.001) for the highest PAS categories, which were also associated with a higher rate of hysterectomy (p < 0.001), blood transfusion (p = 0.002) and admission to ITU or HDU (p < 0.001) and longer postoperative admission of 3 (1-9) days for PAS0 vs 3 (2-12) for PAS1 vs 4.5 (3-6) for PAS2 vs 5 (3-22) for PAS3, p = 0.02.

Conclusion: Perioperative complications are closely associated with PAS stage. This information is useful for counselling women and may be important in allocating staff and infrastructure resources at the time of delivery.
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http://dx.doi.org/10.1016/j.ejogrb.2020.04.038DOI Listing
July 2020

Acute cardiovascular changes in women undergoing in vitro fertilisation (IVF), a systematic review and meta-analysis.

Eur J Obstet Gynecol Reprod Biol 2020 May 17;248:245-251. Epub 2020 Feb 17.

Imperial College London: Institute of Developmental and Reproductive Biology, Hammersmith Hospital, Du Cane Rd, London, W12 OHS, United Kingdom; Queen Charlotte's & Chelsea Hospital, Du Cane Rd, London, W12 OHS, United Kingdom. Electronic address:

Objectives: Ovarian stimulation during fertility treatment leads to profound maternal physiological changes. Women undergoing in vitro fertilisation (IVF) may be at an increased risk of future cardiovascular morbidity, though little is known about the effects on maternal cardiovascular function. We aim to systematically review whether IVF treatment is associated with changes in maternal haemodynamic parameters, and the effects of different protocols.

Study Design: A systematic review and meta-analysis of English language studies identified on Medline and EMBASE database, between 1978, to 2019. Search terms: IVF, maternal haemodynamics, and cardiovascular. Studies reporting on ovulation induction, intrauterine insemination, and oocyte donation were excluded. Methodological quality was assessed by using the adapted Critical Appraisal Skills Programme (CASP) checklist. A meta-analysis was conducted for blood pressure and heart rate on patients undergoing the long GnRH agonist protocol according to Cochrane guidelines. We considered four time points in the IVF cycle, in chronological order: pre-treatment, pituitary down regulation, peak oestradiol and the luteal phase.

Results: Nine suitable studies were identified; four fulfilled the criteria for meta-analysis. Two studies measuring heart rate found a significant increase in heart rate from pituitary down-regulation to peak estradiol levels, which was supported by the meta-analysis (3.78 ± 2.18 (p= < 0.0001)). Three studies reported a significant decrease in blood pressure from baseline, with those suitable for meta-analysis showing a significant decrease in mean arterial pressure (-2.08 ± 1.79 (p= < 0.0001)). Cardiac functional changes were reported for all studies and the changes depended on the type of protocol used.

Conclusions: In Vitro Fertilisation leads to acute changes in maternal haemodynamics at different time points of the stimulation protocol. We found an increase in heart rate from pituitary down-regulation to peak estradiol levels and a significant decrease in blood pressure from baseline or pituitary down-regulation to the luteal phase. Cardiac functional changes were reported for all studies on the agonist protocol, but no significant changes were found using the antagonist protocol. It remains unclear as to whether these acute changes were associated with pregnancy complications or chronic cardiovascular sequelae.
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http://dx.doi.org/10.1016/j.ejogrb.2020.01.033DOI Listing
May 2020

Peri-implantation urinary hormone monitoring distinguishes between types of first-trimester spontaneous pregnancy loss.

Paediatr Perinat Epidemiol 2020 09 13;34(5):495-503. Epub 2020 Feb 13.

Institute for Reproductive and Developmental Biology, Imperial College, London, UK.

Background: Lutenising hormone (LH) and human chorionic gonadotropin (hCG) hormone are useful biochemical markers to indicate ovulation and embryonic implantation, respectively. We explored "point-of-care" LH and hCG testing using a digital home-testing device in a cohort trying to conceive.

Objective: To determine conception and spontaneous pregnancy loss rates, and to assess whether trends in LH-hCG interval which are known to be associated with pregnancy viability could be identified with point-of-care testing.

Methods: We recruited healthy women aged 18-44 planning a pregnancy. Participants used a home monitor to track LH and hCG levels for 12 menstrual cycles or until pregnancy was conceived. Pregnancy outcomes (viable, clinical miscarriage, or biochemical pregnancy loss) were recorded. Monitor data were analysed by a statistician blinded to pregnancy outcome.

Results: From 387 recruits, there were 290 pregnancies with known outcomes within study timeline. Adequate monitor data for analysis were available for 150 conceptive cycles. Overall spontaneous first-trimester pregnancy loss rate was 30% with clinically recognised miscarriage rate of 17%. The difference to LH-hCG interval median had wider spread for biochemical losses (0.5-8.5 days) compared with clinical miscarriage (0-5 days) and viable pregnancies (0-6 days). Fixed effect hCG profile change distinguished between pregnancy outcomes from as early as day-2 post-hCG rise from baseline.

Conclusions: The risk of first-trimester spontaneous pregnancy loss in our prospective cohort is comparable to studies utilising daily urinary hCG collection and laboratory assays. A wider LH-hCG interval range is associated with biochemical pregnancy loss and may relate to late or early implantation. Although early hCG changes discriminate between pregnancies that will miscarry from viable pregnancies, this point-of-care testing model is not sufficiently developed to be predictive.
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http://dx.doi.org/10.1111/ppe.12613DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7496486PMC
September 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

Burnout, well-being and defensive medical practice among obstetricians and gynaecologists in the UK: cross-sectional survey study.

BMJ Open 2019 11 25;9(11):e030968. Epub 2019 Nov 25.

Department of Development & Regeneration, KU Leuven, Leuven, Belgium.

Objectives: To determine the prevalence of burnout in doctors practising obstetrics and gynaecology, and assess the association with defensive medical practice and self-reported well-being.

Design: Nationwide online cross-sectional survey study; December 2017-March 2018.

Setting: Hospitals in the UK.

Participants: 5661 practising obstetrics and gynaecology consultants, specialty and associate specialist doctors and trainees registered with the Royal College of Obstetricians and Gynaecologists.

Primary And Secondary Outcome Measures: Prevalence of burnout using the Maslach Burnout Inventory and defensive medical practice (avoiding cases or procedures, overprescribing, over-referral) using a 12-item questionnaire. The odds ratios (OR) of burnout with defensive medical practice and self-reported well-being.

Results: 3102/5661 doctors (55%) completed the survey. 3073/3102 (99%) met the inclusion criteria (1462 consultants, 1357 trainees and 254 specialty and associate specialist doctors). 1116/3073 (36%) doctors met the burnout criteria, with levels highest amongst trainees (580/1357 (43%)). 258/1116 (23%) doctors with burnout reported increased defensive practice compared with 142/1957 (7%) without (adjusted OR 4.35, 95% CI 3.46 to 5.49). ORs of burnout with well-being items varied between 1.38 and 6.37, and were highest for anxiety (3.59, 95% CI 3.07 to 4.21), depression (4.05, 95% CI 3.26 to 5.04) and suicidal thoughts (6.37, 95% CI 95% CI 3.95 to 10.7). In multivariable logistic regression, being of younger age, white or 'other' ethnicity, and graduating with a medical degree from the UK or Ireland had the strongest associations with burnout.

Conclusions: High levels of burnout were observed in obstetricians and gynaecologists and particularly among trainees. Burnout was associated with both increased defensive medical practice and worse doctor well-being. These findings have implications for the well-being and retention of doctors as well as the quality of patient care, and may help to inform the content of future interventions aimed at preventing burnout and improving patient safety.
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http://dx.doi.org/10.1136/bmjopen-2019-030968DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6887071PMC
November 2019

The relationship between maternal characteristics and carotid intima-media thickness using an automated ultrasound technique.

Hypertens Pregnancy 2019 Nov 19;38(4):252-259. Epub 2019 Sep 19.

Imperial College School of Medicine, Imperial College London , London , UK.

To investigate CIMT and its relationship with maternal demographic characteristics in healthy pregnancy. CIMT was measured using an au. CIMT showed no relationship with gestational age (rho=-0.124, p=0.335), parity (Z=-0.055, p=0.960) and MAP (rho=0.110, p=0.393). A relationship was found between CIMT and maternal age (rho=0.277, p=0.028), booking BMI (rho=0.278, p=0.027), and BMI at time of study (rho=0.287, p=0.023). CIMT ranged from 0.30-0.80mm, the 97.5th percentile was 0.63 mm. In healthy pregnancy, we reported CIMT was related to BMI and maternal age but not parity or gestational age.
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http://dx.doi.org/10.1080/10641955.2019.1667382DOI Listing
November 2019

Sex differences in fetal growth and immediate birth outcomes in a low-risk Caucasian population.

Biol Sex Differ 2019 09 9;10(1):48. Epub 2019 Sep 9.

KU Leuven Department of Development and Regeneration: Pregnancy, Fetus and Neonate, Gynaecology and Obstetrics, University Hospitals Leuven, Herestraat 49, 3000, Leuven, Belgium.

Background: According to the WHO Multicentre Growth Reference Study Group recommendations, boys and girls have different growth trajectories after birth. Our aim was to develop gender-specific fetal growth curves in a low-risk population and to compare immediate birth outcomes.

Methods: First, second, and third trimester fetal ultrasound examinations were conducted between 2002 and 2012. The data was selected using the following criteria: routine examinations in uncomplicated singleton pregnancies, Caucasian ethnicity, and confirmation of gestational age by a crown-rump length (CRL) measurement in the first trimester. Generalized Additive Model for Location, Scale and Shape (GAMLSS) was used to align the time frames of the longitudinal fetal measurements, corresponding with the methods of the postnatal growth curves of the WHO MGRS Group.

Results: A total of 27,680 complete scans were selected from the astraia© ultrasound database representing 12,368 pregnancies. Gender-specific fetal growth curves for biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC), and femur length (FL) were derived. The HC and BPD were significantly larger in boys compared to girls from 20 weeks of gestation onwards (p < 0.001) equating to a 3-day difference at 20-24 weeks. Boys were significantly heavier, longer, and had greater head circumference than girls (p < 0.001) at birth. The Apgar score at 1 min (p = 0.01) and arterial cord pH (p < 0.001) were lower in boys.

Conclusions: These longitudinal fetal growth curves for the first time allow integration with neonatal and pediatric WHO gender-specific growth curves. Boys exceed head growth halfway of the pregnancy, and immediate birth outcomes are worse in boys than girls. Gender difference in intrauterine growth is sufficiently distinct to have a clinically important effect on fetal weight estimation but also on the second trimester dating. Therefore, these differences might already play a role in early fetal or immediate neonatal management.
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http://dx.doi.org/10.1186/s13293-019-0261-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6734449PMC
September 2019

Effects of Antenatal Betamethasone on Fetal Doppler Indices and Short Term Fetal Heart Rate Variation in Early Growth Restricted Fetuses.

Ultraschall Med 2021 Feb 2;42(1):56-64. Epub 2019 Sep 2.

Department of Surgery and Cancer, Imperial College London, United Kingdom of Great Britain and Northern Ireland.

Purpose:  To investigate the effects of the antenatal administration of betamethasone on fetal Doppler and short term fetal heart rate variation (CTG-STV) in early growth restricted (FGR) fetuses.

Materials And Methods:  Post hoc analysis of data derived from the TRUFFLE study, a prospective, multicenter, randomized management trial of severe early onset FGR. Repeat Doppler and CTG-STV measurements between the last recording within 48 hours before the first dose of betamethasone (baseline value) and for 10 days after were evaluated. Multilevel analysis was performed to analyze the longitudinal course of the umbilico-cerebral ratio (UC ratio), the ductus venosus pulsatility index (DVPIV) and CTG-STV.

Results:  We included 115 fetuses. A significant increase from baseline in CTG-STV was found on day + 1 (p = 0.019) but no difference thereafter. The DVPIV was not significantly different from baseline in any of the 10 days following the first dose of betamethasone (p = 0.167). Multilevel analysis revealed that, over 10 days, the time elapsed from antenatal administration of betamethasone was significantly associated with a decrease in CTG-STV (p = 0.045) and an increase in the DVPIV (p = 0.001) and UC ratio (p < 0.001).

Conclusion:  Although steroid administration in early FGR has a minimal effect on increasing CTG-STV one day afterwards, the effects on Doppler parameters were extremely slight with regression coefficients of small magnitude suggesting no clinical significance, and were most likely related to the deterioration with time in FGR. Hence, arterial and venous Doppler assessment of fetal health remains informative following antenatal steroid administration to accelerate fetal lung maturation.
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http://dx.doi.org/10.1055/a-0972-1098DOI Listing
February 2021

Uterine and fetal placental Doppler indices are associated with maternal cardiovascular function: Reply.

Am J Obstet Gynecol 2019 09 15;221(3):291-292. Epub 2019 Jun 15.

Department of Surgery and Cancer, Imperial College, London, UK. Electronic address:

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http://dx.doi.org/10.1016/j.ajog.2019.06.012DOI Listing
September 2019

The impact of cross-border IVF on maternal and neonatal outcomes in multiple pregnancies: Experience from a UK fetal medicine service.

Eur J Obstet Gynecol Reprod Biol 2019 Jul 2;238:63-67. Epub 2019 May 2.

Centre for Fetal Care, Queen Charlotte's & Chelsea Hospital, Imperial College Healthcare NHS trust, London, United Kingdom; Imperial College London, United Kingdom. Electronic address:

Objectives: To determine whether women seeking NHS care for IVF multiple pregnancies were more likely to have sought IVF treatment overseas and whether this was associated with different maternal and neonatal outcomes.

Study Design: A single large tertiary centre, for perinatal care in northwest London. Sixty-five women were referred to our fetal medicine centre, between 2012-2016, with IVF conceived multiple pregnancies.

Inclusion Criteria: In Vitro fertilisation and conception of twins/ triplets/quadruplets.

Exclusion Criteria: Intra-uterine insemination, ovulation induction, Clomid-conception and singleton pregnancies. The primary outcome measure was the Country where IVF treatment was performed. The secondary outcomes measures included the specifics of IVF treatment (e.g. number of embryos transferred), subsequent pregnancy outcomes (e.g. live-births and prematurity) and neonatal outcomes (e.g. length and cost of care).

Results And Conclusion: Thirty-eight women had IVF overseas; they were older and had more pre-existing medical conditions. Eleven pregnancies used donor embryos, of which ten were from overseas treatment. 75% of women treated overseas conceived a triplet or higher order pregnancy compared to fewer than 10% of women who conceived in the UK. Almost half of all women treated overseas had more than two embryos transferred. Overseas IVF pregnancies had poorer obstetric and neonatal outcomes: 24% of live born babies died in the neonatal period compared to 0% in the UK group. The average neonatal costs per baby born from overseas IVF were £20, 600: two-and-a-half times higher than for those whose mothers conceived in the UK. Higher order multiple pregnancies are greatly over-represented by those undergoing IVF in overseas clinics. These are associated with poorer obstetric and neonatal outcomes. Perhaps paradoxically, improving NHS provision of fertility services might improve outcomes for the mother and babies while reducing the long-term burden to both fertility patients and the NHS.
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http://dx.doi.org/10.1016/j.ejogrb.2019.04.030DOI Listing
July 2019

Comparing the relation between ultrasound-estimated fetal weight and birthweight in cohort of small-for-gestational-age fetuses.

Acta Obstet Gynecol Scand 2019 11 6;98(11):1435-1441. Epub 2019 Jun 6.

Queen Charlotte's and Chelsea Hospital, London, UK.

Introduction: Small-for-gestational-age (SGA) confers a higher perinatal risk of adverse outcomes. Birthweight cannot be accurately measured until delivery, therefore accurate estimated fetal weight (EFW) based on ultrasonography is important in identifying this high-risk population. We aimed to establish the sensitivity of detecting SGA infants antenatally in a unit with a selective third-trimester ultrasound policy and to investigate the association between EFW and birthweight in these babies.

Material And Methods: A retrospective cohort study was conducted on non-anomalous singleton pregnancies delivered after 36 weeks of gestation where SGA (<10th percentile) was diagnosed at delivery. The EFW at the time of the third-trimester ultrasound scan was recorded using standard Hadlock formulae.

Results: In 2017, there were 8392 non-anomalous singleton pregnancies live born after 36 weeks, excluding late bookers. 797 were live-born SGA <10th percentile for birthweight and 464 <5th percentile, who met our inclusion criteria. The antenatal detection rate of SGA was 19.6% for babies with birthweight <10th percentile and 24.1% <5th percentile. There was a significant correlation between the EFW and birthweight of fetuses undergoing ultrasound assessment within 2 weeks of delivery (P < .001, r = 0.73 (Pearson correlation). For these cases, EFW was greater than the birthweight in 65% of cases. After adjusting all EFWs using the discrepancy between EFW and actual birthweight for those babies born within 48 hours of the scan, the mean difference between the birthweight and adjusted EFW 7 days before delivery was 111 g (95% CI 87-136 g) and at 14 days was 200 g (95% CI 153-248 g). Despite adjusting the EFW, 61/213 cases (28.6%) apparently lost weight between the ultrasound scan and delivery.

Conclusions: Small-for-gestational-age infants with a birthweight <10th percentile are poorly identified antenatally with little improvement for those <5th percentile. In SGA babies, ultrasound EFW overestimated birthweight. Discrepancies between birthweight and EFW are not explicable only by the limitations of third-trimester sonography, a reduction in fetal weight close to delivery in a proportion of liveborn SGA babies is plausible.
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http://dx.doi.org/10.1111/aogs.13645DOI Listing
November 2019

Maternal and fetal cardiometabolic recovery following ultrasound-guided high-intensity focused ultrasound placental vascular occlusion.

J R Soc Interface 2019 05;16(154):20190013

2 Institute of Reproductive and Developmental Biology, Imperial College London , London W12 0HS , UK.

High-intensity focused ultrasound (HIFU) is a non-invasive method of selective placental vascular occlusion, providing a potential therapy for conditions such as twin-twin transfusion syndrome. In order to translate this technique into human studies, evidence of prolonged fetal recovery and maintenance of a healthy fetal physiology following exposure to HIFU is essential. At 116 ± 2 days gestation, 12 pregnant ewes were assigned to control ( n = 6) or HIFU vascular occlusion ( n = 6) groups and anaesthetized. Placental blood vessels were identified using colour Doppler ultrasound; HIFU-mediated vascular occlusion was performed through intact maternal skin (1.66 MHz, 5 s duration, in situ I 1.8-3.9 kW cm). Unidentifiable colour Doppler signals in targeted vessels following HIFU exposure denoted successful occlusion. Ewes and fetuses were then surgically instrumented with vascular catheters and transonic flow probes and recovered from anaesthesia. A custom-made wireless data acquisition system, which records continuous maternal and fetal cardiovascular data, and daily blood sampling were used to assess wellbeing for 20 days, followed by post-mortem examination. Based on a comparison of pre- and post-treatment colour Doppler imaging, 100% (36/36) of placental vessels were occluded following HIFU, and occlusion persisted for 20 days. All fetuses survived. No differences in maternal or fetal blood pressure, heart rate, heart rate variability, metabolic status or oxygenation were observed between treatment groups. There was evidence of normal fetal maturation and no evidence of chronic fetal stress. There were no maternal injuries and no placental vascular haemorrhage. There was both a uterine and fetal burn, which did not result in any obstetric or fetal complications. This study demonstrates normal long-term recovery of fetal sheep from exposure to HIFU-mediated placental vascular occlusion and underlines the potential of HIFU as a potential non-invasive therapy in human pregnancy.
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http://dx.doi.org/10.1098/rsif.2019.0013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6544891PMC
May 2019

Prediction of mode of delivery using the first ultrasound-based "intrapartum app".

Am J Obstet Gynecol 2019 08 27;221(2):163-166. Epub 2019 Mar 27.

Department of Cancer and Surgery, Imperial College London, London, UK; Centre for Fetal Care, Queen Charlotte's and Chelsea Hospital, Imperial College Healthcare NHS Trust, London, UK; Department of Development & Regeneration, KU Leuven, Leuven, Belgium. Electronic address:

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http://dx.doi.org/10.1016/j.ajog.2019.03.019DOI Listing
August 2019

The use of actograph in the assessment of fetal well-being.

J Matern Fetal Neonatal Med 2020 Jun 5;33(12):2116-2121. Epub 2019 Mar 5.

Centre for Fetal Care, Imperial College London, Queen Charlotte's and Chelsea Hospital, Imperial College Healthcare National Health Service Trust, London, UK.

Third trimester maternal perception of fetal movements is often used to assess fetal well-being. However, its true clinical value is unknown, primarily because of the variability in subjective quantification. The actograph, a technology available on most cardiotocograph machines, quantifies movements, but has never previously been investigated in relation to fetal health and existing monitoring devices. The objective of this study was to quantify actograph output in healthy third trimester pregnancies and investigate this in relation to other methods of assessing fetal well-being. Forty-two women between 24 and 34 weeks of gestation underwent ultrasound scan followed by a computerized cardiotocograph (CTG). Post capture analysis of the actograph recording was performed and expressed as a percentage of activity over time. The actograph output results were analyzed in relation to Doppler, ultrasound and CTG findings expressed as z-score normalized for gestation. There was a significant association between actograph output recording and estimated fetal weight Z-score ( = 0.546, ≤ .005). This activity was not related to estimated fetal weight. Increased actograph activity was negatively correlated with umbilical artery pulsatility index -score ( = -0.306, = .049) and middle cerebral artery pulsatility index Z-score ( = -0.390, = .011). Fetal movements assessed by the actograph are associated both with fetal size in relation to gestation and fetoplacental Doppler parameters. It is not the case that larger babies move more, however, as the relationship with actograph output related only to estimated fetal weight z-score. These findings suggest a plausible link between the frequency of fetal movements and established markers of fetal health.The objective of this study was to quantify actograph output in healthy third trimester pregnancies and investigate this in relation to other methods of assessing fetal well-being. This is a widely available method of assessing fetal movements objectively, which has been shown to be an important marker of fetal health. This research is novel in the fact that actograph has never been truly investigated in relation to fetal well-being, despite being available on most cardiotocograph (CTG) machines.Our results show that fetal movements assessed by the actograph are associated both with fetal size in relation to gestation and fetoplacental Doppler parameters. If this proves to be true, smaller babies that move less maybe at particular perinatal risk.
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http://dx.doi.org/10.1080/14767058.2018.1540584DOI Listing
June 2020

The DESiGN trial (DEtection of Small for Gestational age Neonate), evaluating the effect of the Growth Assessment Protocol (GAP): study protocol for a randomised controlled trial.

Trials 2019 Mar 4;20(1):154. Epub 2019 Mar 4.

Department of Women and Children's Health, School of Life Course Sciences, Faculty of Life Sciences and Medicine, King's College London, Women's Health Academic Centre KHP, 10th Floor North Wing, St. Thomas' Hospital, Westminster Bridge Road, London, SE1 7EH, UK.

Background: Stillbirth rates in the United Kingdom (UK) are amongst the highest of all developed nations. The association between small-for-gestational-age (SGA) foetuses and stillbirth is well established, and observational studies suggest that improved antenatal detection of SGA babies may halve the stillbirth rate. The Growth Assessment Protocol (GAP) describes a complex intervention that includes risk assessment for SGA and screening using customised fundal-height growth charts. Increased detection of SGA from the use of GAP has been implicated in the reduction of stillbirth rates by 22%, in observational studies of UK regions where GAP uptake was high. This study will be the first randomised controlled trial examining the clinical efficacy, health economics and implementation of the GAP programme in the antenatal detection of SGA.

Methods/design: In this randomised controlled trial, clusters comprising a maternity unit (or National Health Service Trust) were randomised to either implementation of the GAP programme, or standard care. The primary outcome is the rate of antenatal ultrasound detection of SGA in infants found to be SGA at birth by both population and customised standards, as this is recognised as being the group with highest risk for perinatal morbidity and mortality. Secondary outcomes include antenatal detection of SGA by population centiles, antenatal detection of SGA by customised centiles, short-term maternal and neonatal outcomes, resource use and economic consequences, and a process evaluation of GAP implementation. Qualitative interviews will be performed to assess facilitators and barriers to implementation of GAP.

Discussion: This study will be the first to provide data and outcomes from a randomised controlled trial investigating the potential difference between the GAP programme compared to standard care for antenatal ultrasound detection of SGA infants. Accurate information on the performance and service provision requirements of the GAP protocol has the potential to inform national policy decisions on methods to reduce the rate of stillbirth.

Trial Registration: Primary registry and trial identifying number: ISRCTN 67698474 . Registered on 2 November 2016.
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http://dx.doi.org/10.1186/s13063-019-3242-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6398257PMC
March 2019

Fetal abdominal cysts: antenatal course and postnatal outcomes.

J Perinat Med 2019 May;47(4):418-421

Centre for Fetal Care, Queen Charlotte's and Chelsea Hospital, Imperial College Healthcare NHS Trust, London, UK.

Background There is little information on which to base the prognostic counselling as to whether an antenatally diagnosed fetal abdominal cyst will grow or shrink, or need surgery. This study aims to provide contemporary data on prenatally diagnosed fetal abdominal cysts in relation to their course and postnatal outcomes. Methods Fetal abdominal cysts diagnosed over 11 years in a single centre were identified. The gestational age at diagnosis and cyst characteristics at each examination were recorded (size, location, echogenity, septation and vascularity) and follow-up data from postnatal visits were collected. Results Eighty abdominal cysts were identified antenatally at 28+4 weeks (range 11+0-38+3). Most (87%) were isolated and the majority were pelvic (52%), simple (87.5%) and avascular (100%). Antenatally, 29% resolved spontaneously; 29% reduced in size; 9% were stable and 33% increased in size. Forty-one percent of cysts under 20 mm diameter increased in size, while only 20% of cysts with a diameter of over 40 mm increased in size. The majority of cysts were ovarian in origin (n=45, 56%), followed by intestinal (n=15, 18%), choledochal (n=3, 4%), liver (n=2, 3%) and renal/adrenal origins (n=2, 3%), respectively. In 16% (n=13), the antenatal diagnosis was not obvious. Seventy-five percent of the cysts that persisted postnatally required surgical intervention. Conclusion Most antenatally diagnosed fetal abdominal cysts were ovarian in origin. Though most disappeared antenatally, nearly three quarters required surgical intervention when present after birth. Cysts of intestinal origin are more difficult to diagnose antenatally and often require surgery.
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http://dx.doi.org/10.1515/jpm-2018-0311DOI Listing
May 2019

The controversial role of the ductus venosus in hypoxic human fetuses.

Acta Obstet Gynecol Scand 2019 07 23;98(7):823-829. Epub 2019 Apr 23.

Department of Clinical Science, Intervention and Technology, Karolinska Institute and Center for Fetal Medicine, Karolinska University Hospital, Stockholm, Sweden.

The ductus venosus plays a critical role in circulatory adaptation to hypoxia in fetal growth restriction but the mechanisms still remain controversial. Increased shunting of blood through the ductus venosus under hypoxic conditions has been shown in animal and human studies. The hemodynamic laws governing the accelerated flow in this vessel suggest that any dilation at its isthmus, which increases the blood flow shunting to the heart, is associated with a low, absent or reversed a-wave and a high pulsatility index. Cardiac dysfunction associated with increased atrial pressure as well as reduced ventricular compliance might be predominant mechanisms determining the profile of ductus venosus velocity waveforms in severe fetal growth restriction with signs of hypoxic compromise. Understanding the pathophysiology of the ductus venosus will underpin translation of the hypotheses developed through biostatistics toward explaining with more confidence Doppler changes in the fetal circulation in predicting clinical outcomes.
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http://dx.doi.org/10.1111/aogs.13572DOI Listing
July 2019

Response to: Vaginal examination and fear of childbirth.

Aust N Z J Obstet Gynaecol 2018 12;58(6):E25

Centre of Fetal Care - Fetal Medicine, Imperial College London, London, UK.

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http://dx.doi.org/10.1111/ajo.12908DOI Listing
December 2018

How to obtain diagnostic planes of the fetal central nervous system using three-dimensional ultrasound and a context-preserving rendering technology.

Am J Obstet Gynecol 2019 03 14;220(3):215-229. Epub 2018 Nov 14.

Centre for Fetal Care, Queen Charlotte's and Chelsea Hospital, Imperial College Healthcare NHS Trust, London, UK; Department of Surgery and Cancer, Imperial College London, UK; Department of Development and Regeneration, KU Leuven, Belgium. Electronic address:

The antenatal evaluation of the fetal central nervous system (CNS) is among the most difficult tasks of prenatal ultrasound (US), requiring technical skills in relation to ultrasound and image acquisition as well as knowledge of CNS anatomy and how this changes with gestation. According to the International Guidelines for fetal neurosonology, the basic assessment of fetal CNS is most frequently performed on the axial planes, whereas the coronal and sagittal planes are required for the multiplanar evaluation of the CNS within the context of fetal neurosonology. It can be even more technically challenging to obtain "nonaxial" views with 2-dimensional (2D) US. The modality of 3-dimensional (3D) US has been suggested as a panacea to overcome the technical difficulties of achieving nonaxial views. The lack of familiarity of most sonologists with the use of 3D US and its related processing techniques may preclude its use even where it could play an important role in complementing antenatal 2D US assessment. Furthermore, once a 3D volume has been acquired, proprietary software allows it to be processed in different ways, leading to multiple ways of displaying and analyzing the same anatomical imaging or plane. These are difficult to learn and time consuming in the absence of specific training. In this article, we describe the key steps for volume acquisition of a 3D US volume, manipulation, and processing with reference to images of the fetal CNS, using a newly developed context-preserving rendering technique.
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http://dx.doi.org/10.1016/j.ajog.2018.11.1088DOI Listing
March 2019

Performance of computerized cardiotocography-based short-term variation in late-onset small-for-gestational-age fetuses and reference ranges for the late third trimester.

Arch Gynecol Obstet 2019 02 16;299(2):353-360. Epub 2018 Nov 16.

Department of Obstetrics and Gynecology, University Hospital rechts der Isar, Technical University of Munich, Ismaninger Str. 22, 81675, Munich, Germany.

Purpose: Fetal Doppler changes are well characterized in early-onset small-for-gestational-age (SGA) and fetal growth restriction (FGR) but less well characterized where the condition is late-onset. The aim of the study was to evaluate the role of computerized CTG (cCTG)-based short-term variation (STV) in late-onset SGA and FGR as an additional monitoring modality and to establish STV reference ranges in late third trimester healthy pregnancies.

Methods: Of 86 late-onset SGA fetuses diagnosed after 32 weeks, 66 were diagnosed with FGR. 138 healthy pregnancies acted as controls. All underwent umbilical artery pulsatility index (PI), middle cerebral artery PI, cerebroplacental ratio and mean uterine artery PI. cCTG recordings were analyzed by Sonicaid FetalCare software for STV calculation as described by Dawes/Redman.

Results: Median interval between inclusion and delivery was 13 (interquantile range = 4-30) days in the FGR group, 22 (12-37) days in the SGA group and 25 (10-40) days in the control group. STV was not different between controls (11.2 ms, 9.7-13.1), late-onset SGA (11.2 ms, 8.1-12.6) and FGR (10.5 ms, 8.5-12.4) fetuses. A greater proportion of late-onset SGA fetuses had STV < 5th percentile (7/86) compared to controls (4/138) (8.1% vs. 2.9%, p = 0.077). In the control group a significant positive correlation was seen between STV, and 1-min (ρ = 0.195, p = 0.026), 5-min (ρ = 0.247, p = 0.004) and 10-min (ρ = 0.211, p = 0.014) Apgar values.

Conclusions: We report no significant difference in STV median values between controls, SGA and FGR pregnancies. However, more SGA fetuses had a low STV compared to controls. Prospective longitudinal studies are needed to investigate if low STV is a useful surveillance method for late-onset FGR.
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http://dx.doi.org/10.1007/s00404-018-4966-3DOI Listing
February 2019

Cardiac output changes from prior to pregnancy to post partum using two non-invasive techniques.

Heart 2019 05 30;105(9):715-720. Epub 2018 Oct 30.

Department of Surgery and Cancer, Imperial College London, London, UK.

Objectives: We aimed to describe cardiac output (CO) trend from prepregnancy to post partum using an inert gas rebreathing (IGR) device and compare these measurements with those obtained by a pulse waveform analysis (PWA) technique, both cross-sectionally and longitudinally.

Methods: Non-smoking healthy women, aged 18-44 years, with body mass index <35 were included in this prospective observational study. CO measurements were collected at different time points (prepregnancy, at four different gestational epochs and post partum) using IGR and PWA. A linear mixed model analysis tested whether the longitudinal change in CO differed between the techniques. Bland-Altman analysis and intraclass correlation coefficient (ICC) were used for cross-sectional and a four-quadrant plot for longitudinal comparisons.

Results: Of the 413 participants, 69 had a complete longitudinal assessment throughout pregnancy. In this latter cohort, the maximum CO rise was seen at 15.2 weeks with IGR (+17.5% from prepregnancy) and at 10.4 weeks with PWA (+7.7% from prepregnancy). Trends differed significantly (p=0.0093). Cross-sectional analysis was performed in the whole population of 413 women: the mean CO was 6.14 L/min and 6.38 L/min for PWA and IGR, respectively, the percentage of error was 46% and the ICC was 0.348, with similar results at all separate time points. Longitudinal concordance was 64%.

Conclusions: Despite differences between devices, the maximum CO rise in healthy pregnancies is more modest and earlier than previously reported. The two methods of CO measurement do not agree closely and cannot be used interchangeably. Technique-specific reference ranges are needed before they can be applied in research and clinical settings.
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http://dx.doi.org/10.1136/heartjnl-2018-313682DOI Listing
May 2019

Uterine and fetal placental Doppler indices are associated with maternal cardiovascular function.

Am J Obstet Gynecol 2019 01 19;220(1):96.e1-96.e8. Epub 2018 Sep 19.

Centre for Fetal Care, Queen Charlotte's and Chelsea Hospital, Imperial College Healthcare NHS Trust, London, United Kingdom; Institute for Reproductive and Developmental Biology, Department of Surgery and Cancer, Imperial College London, London, United Kingdom; Department of Development and Regeneration, KU Leuven, Leuven, Belgium. Electronic address:

Background: The mechanism underlying fetal-placental Doppler index changes in preeclampsia and/or fetal growth restriction are unknown, although both are associated with maternal cardiovascular dysfunction.

Objective: We sought to investigate whether there was a relationship between maternal cardiac output and vascular resistance and fetoplacental Doppler findings in healthy and complicated pregnancy.

Study Design: Women with healthy pregnancies (n=62), preeclamptic pregnancies (n=13), preeclamptic pregnancies with fetal growth restriction (n=15), or fetal growth restricted pregnancies (n=17) from 24-40 weeks gestation were included. All of them underwent measurement of cardiac output with the use of an inert gas rebreathing technique and derivation of peripheral vascular resistance. Uterine and fetal Doppler indices were recorded; the latter were z scored to account for gestation. Associations were determined by polynomial regression analyses.

Results: Mean uterine artery pulsatility index was higher in fetal growth restriction (1.37; P=.026) and preeclampsia+fetal growth restriction (1.63; P=.001) but not preeclampsia (0.92; P=1) compared with control subjects (0.8). There was a negative relationship between uterine pulsatility index and cardiac output (r=0.101; P=.025) and umbilical pulsatility index z score and cardiac output (r=0.078; P=.0015), and there were positive associations between uterine pulsatility index and peripheral vascular resistance (r=0.150; P=.003) and umbilical pulsatility index z score and peripheral vascular resistance (r= 0.145; P=.001). There was no significant relationship between cardiac output and peripheral vascular resistance with cerebral Doppler indices.

Conclusion: Uterine artery Doppler change is abnormally elevated in fetal growth restriction with and without preeclampsia, but not in preeclampsia, which may explain the limited sensitivity of uterine artery Doppler changes for all these complications when considered in aggregate. Furthermore, impedance within fetoplacental arterial vessels is at least, in part, associated with maternal cardiovascular function. This relationship may have important implications for fetal surveillance and would inform therapeutic options in those pathologic pregnancy conditions currently, and perhaps erroneously, attributed purely to placental maldevelopment. Uterine and fetal placental Doppler indices are associated significantly with maternal cardiovascular function. The classic description of uterine and fetal Doppler changes being initiated by placental maldevelopment is a less plausible explanation for the pathogenesis of the conditions than that relating to maternal cardiovascular changes.
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http://dx.doi.org/10.1016/j.ajog.2018.09.017DOI Listing
January 2019

Trans-abdominal in vivo placental vessel occlusion using High Intensity Focused Ultrasound.

Sci Rep 2018 09 11;8(1):13631. Epub 2018 Sep 11.

Institute of Reproductive and Developmental Biology, Imperial College London, London, W12 0HS, UK.

Pre-clinically, High Intensity Focused Ultrasound (HIFU) has been shown to safely and effectively occlude placental blood vessels in the acute setting, when applied through the uterus. However, further development of the technique to overcome the technical challenges of targeting and occluding blood vessels through intact skin remains essential to translation into human studies. So too does the assessment of fetal wellbeing following this procedure, and demonstration of the persistence of vascular occlusion. At 115 ± 10 d gestational age (term~147 days) 12 pregnant sheep were exposed to HIFU (n = 6), or to a sham (n = 6) therapy through intact abdominal skin (1.66 MHz, 5 s duration, in situ I 1.3-4.4 kW.cm). Treatment success was defined as undetectable colour Doppler signal in the target placental vessel following HIFU exposures. Pregnancies were monitored for 21 days using diagnostic ultrasound from one day before HIFU exposure until term, when post-mortem examination was performed. Placental vessels were examined histologically for evidence of persistent vascular occlusion. HIFU occluded 31/34 (91%) of placental vessels targeted, with persistent vascular occlusion evident on histological examination 20 days after treatment. The mean diameter of occluded vessels was 1.4 mm (range 0.3-3.3 mm). All pregnancies survived until post mortem without evidence of significant maternal or fetal iatrogenic harm, preterm labour, maternal or fetal haemorrhage or infection. Three of six ewes exposed to HIFU experienced abdominal skin burns, which healed without intervention within 21 days. Mean fetal weight, fetal growth velocity and other measures of fetal biometry were not affected by exposure to HIFU. Fetal Doppler studies indicated a transient increase in the umbilical artery pulsatility index (PI) and a decrease in middle cerebral artery PI as a result of general anaesthesia, which was not different between sham and treatment groups. We report the first successful application of fully non-invasive HIFU for occlusion of placental blood flow in a pregnant sheep model, with a low risk of significant complications. This proof of concept study demonstrates the potential of this technique for clinical translation.
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http://dx.doi.org/10.1038/s41598-018-31914-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6134117PMC
September 2018