Publications by authors named "Christoph C Lees"

68 Publications

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejogrb.2020.12.023DOI Listing
February 2021

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
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.
View Article and Find Full Text PDF

Download full-text PDF

Source
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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejogrb.2020.04.038DOI Listing
July 2020

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/a-0972-1098DOI Listing
February 2021

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1098/rsif.2019.0013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6544891PMC
May 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/14767058.2018.1540584DOI Listing
June 2020

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
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.
View Article and Find Full Text PDF

Download full-text PDF

Source
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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-018-31914-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6134117PMC
September 2018

Ultrasound is better tolerated than vaginal examination in and before labour.

Aust N Z J Obstet Gynaecol 2019 06 19;59(3):362-366. Epub 2018 Jul 19.

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

Background: Intrapartum ultrasound has been proposed as a method of assessing labour progress but its acceptability has not been comprehensively assessed.

Aims: We evaluated the acceptability of intrapartum ultrasound in women having vaginal examination (VE) and ultrasound (US) assessment (transabdominal (TA) and transperineal (TP)) prior to delivery, with and without regional analgesia (RA).

Materials And Methods: Women at 24-42 weeks gestation were included in a prospective observational cohort study. The acceptability of digital VE and TP US were assessed pre- and post-examination using the modified validated Wijma Delivery Experience Questionnaire. Acceptability scores ranged 6-36 (6 being most and 36 being least positive) in six domains: positive-trust and relax, negative-harmful to baby, worrying, painful, intrusive.

Results: Of 119 women recruited, 104 completed both pre- and post-assessment questionnaires. Eighty-nine per cent of women were nulliparous with median gestation 40 + 2 weeks (25-42 ). Thirty-two per cent had RA before assessment, 91% in total. The combined acceptability scores of both negative and positive experiences (6 = most acceptable, 36 = least acceptable) for VE and US pre-assessment were 15 and 7 respectively (P < 0.0001: Mann-Whitney U-test). VE was associated with less positive / more negative domain scoring post-assessment 12 and 6, respectively (P < 0.0001). Although RA made no difference to the perceived experience pre-VE (P = 0.9), post-VE, women with RAs considered VEs more acceptable than those without RA (P = 0.0022).

Conclusion(s): This is the first study to comprehensively assess the acceptability of VE and intrapartum US. US assessment prior to delivery is more acceptable than VE. RA ameliorated the negative experience of the VE post-assessment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ajo.12864DOI Listing
June 2019

Etiology and Prognosis of Severe Ventriculomegaly Diagnosed at Late Gestation.

Ultraschall Med 2018 Dec 5;39(6):675-689. Epub 2018 Jul 5.

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

Objectives:  We sought to assess the causes and outcomes of severe VM diagnosed de novo after 24 weeks of gestation where a mid-trimester anomaly scan was described as normal.

Methods:  Multicenter retrospective study of five European fetal medicine centers. The inclusion criteria were normal anatomy at the mid-trimester scan, uni/bilateral finding of posterior ventricle measuring ≥ 15 mm after 24 weeks with neonatal and postnatal pediatric and/or neurological assessment data.

Results:  Of 74 potentially eligible cases, 10 underwent termination, the outcome was missing in 19 cases and there was 1 neonatal death. Therefore, 44 formed the study cohort with a median gestation at diagnosis of 32 + 0 weeks (25 + 6 - 40 + 5). VM was unilateral in five cases. Agenesis of the corpus callosum (ACC) and grade III/IV intraventricular hemorrhage (IVH) accounted for 14 cases each. ACC was isolated in 9 fetuses. Obstructive abnormalities included 5 arachnoid and 1 cavum velum interpositum cyst. Four fetuses had an associated suspected or confirmed genetic condition, 2 congenital infections, 1 abnormal cortical development and the etiology was unknown in 3/44. Postnatal assessment at median 20 months (3 - 96) showed 22/44 (50 %) normal, 7 (16 %) mildly abnormal and 15 (34 %) severely abnormal neurodevelopmental outcomes.

Conclusion:  One half of babies with severe VM diagnosed after 24 weeks have normal infant outcome with ACC and IVH representing the most common causes. Etiology is the most important factor affecting the prognosis of fetuses with severe VM diagnosed at late gestation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/a-0627-7173DOI Listing
December 2018

Association Between Prepregnancy Cardiovascular Function and Subsequent Preeclampsia or Fetal Growth Restriction.

Hypertension 2018 08 2;72(2):442-450. Epub 2018 Jul 2.

From the Institute for Reproductive and Developmental Biology, Imperial College, London, United Kingdom (F.L.F., G.M., S.C., D.A.M., P.R.B., C.C.L.)

Preeclampsia and fetal growth restriction during pregnancy are associated with increased risk of maternal cardiovascular disease later in life. It is unclear whether this association is causal or driven by similar antecedent risk factors. Clarification requires recruitment before conception which is methodologically difficult with high attrition rates and loss of outcome numbers to nonconception/miscarriage. Few prospective studies have, therefore, been adequately powered to address these questions. We recruited 530 healthy women (mean age: 35.0 years) intending to conceive and assessed cardiac output, cardiac index, stroke volume, total peripheral resistance, mean arterial pressure, and heart rate before pregnancy. Participants were followed to completion of subsequent pregnancy with repeat longitudinal assessments. Of 356 spontaneously conceived pregnancies, 15 (4.2%) were affected by preeclampsia and fetal growth restriction. Women who subsequently developed preeclampsia/fetal growth restriction had lower preconception cardiac output (4.9 versus 5.8 L/min; =0.002) and cardiac index (2.9 versus 3.3 L/min per meter; =0.031) while mean arterial pressure (87.1 versus 82.3 mm Hg; =0.05) and total peripheral resistance (1396.4 versus 1156.1 dynes sec cm; <0.001) were higher. Longitudinal trajectories for cardiac output and total peripheral resistance were similar between affected and healthy pregnancies, but the former group showed a more exaggerated fall in mean arterial pressure in the first trimester, followed by a steeper rise and a steeper fall to postpartum values. Significant relationships were observed between cardiac output, total peripheral resistance, and mean arterial pressure and gestational epoch. We conclude that in healthy women, an altered prepregnancy hemodynamic phenotype is associated with the subsequent development of preeclampsia/fetal growth restriction.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/HYPERTENSIONAHA.118.11092DOI Listing
August 2018

Performance of a wearable acoustic system for fetal movement discrimination.

PLoS One 2018 7;13(5):e0195728. Epub 2018 May 7.

Department of Bioengineering, Imperial College London, London, United Kingdom.

Fetal movements (FM) are a key factor in clinical management of high-risk pregnancies such as fetal growth restriction. While maternal perception of reduced FM can trigger self-referral to obstetric services, maternal sensation is highly subjective. Objective, reliable monitoring of fetal movement patterns outside clinical environs is not currently possible. A wearable and non-transmitting system capable of sensing fetal movements over extended periods of time would be extremely valuable, not only for monitoring individual fetal health, but also for establishing normal levels of movement in the population at large. Wearable monitors based on accelerometers have previously been proposed as a means of tracking FM, but such systems have difficulty separating maternal and fetal activity and have not matured to the level of clinical use. We introduce a new wearable system based on a novel combination of accelerometers and bespoke acoustic sensors as well as an advanced signal processing architecture to identify and discriminate between types of fetal movements. We validate the system with concurrent ultrasound tests on a cohort of 44 pregnant women and demonstrate that the garment is capable of both detecting and discriminating the vigorous, whole-body 'startle' movements of a fetus. These results demonstrate the promise of multimodal sensing for the development of a low-cost, non-transmitting wearable monitor for fetal movements.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0195728PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5937742PMC
July 2018

Early and late preeclampsia are characterized by high cardiac output, but in the presence of fetal growth restriction, cardiac output is low: insights from a prospective study.

Am J Obstet Gynecol 2018 05 21;218(5):517.e1-517.e12. Epub 2018 Feb 21.

Centre for Fetal Care, Queen Charlotte's and Chelsea Hospital, Imperial College Healthcare National Health Service 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: Preeclampsia and fetal growth restriction are considered to be placentally mediated disorders. The clinical manifestations are widely held to relate to gestation age at onset with early- and late-onset preeclampsia considered to be phenotypically distinct. Recent studies have reported conflicting findings in relation to cardiovascular function, and in particular cardiac output, in preeclampsia and fetal growth restriction.

Objective: We conducted this study to examine the possible relation between cardiac output and peripheral vascular resistance in preeclampsia and fetal growth restriction.

Study Design: We investigated maternal cardiovascular function in relation to clinical subtype in 45 pathological pregnancies (14 preeclampsia only, 16 fetal growth restriction only, 15 preeclampsia and fetal growth restriction) and compared these with 107 healthy person observations. Cardiac output was the primary outcome measure and was assessed using an inert gas-rebreathing method (Innocor), from which peripheral vascular resistance was derived; arterial function was assessed by Vicorder, a cuff-based oscillometric device. Cardiovascular parameters were normalized for gestational age in relation to healthy pregnancies using Z scores, thus allowing for comparison across the gestational range of 24-40 weeks.

Results: Compared with healthy control pregnancies, women with preeclampsia had higher cardiac output Z scores (1.87 ± 1.35; P = .0001) and lower peripheral vascular resistance Z scores (-0.76 ± 0.89; P = .025); those with fetal growth restriction had higher peripheral vascular resistance Z scores (0.57 ± 1.18; P = .04) and those with both preeclampsia and fetal growth restriction had lower cardiac output Z scores (-0.80 ± 1.3 P = .007) and higher peripheral vascular resistance Z scores (2.16 ± 1.96; P = .0001). These changes were not related to gestational age of onset. All those affected by preeclampsia and/or fetal growth restriction had abnormally raised augmentation index and pulse wave velocity. Furthermore, in preeclampsia, low cardiac output was associated with low birthweight and high cardiac output with high birthweight (r = 0.42, P = .03).

Conclusion: Preeclampsia is associated with high cardiac output, but if preeclampsia presents with fetal growth restriction, the opposite is true; both conditions are nevertheless defined by hypertension. Fetal growth restriction without preeclampsia is associated with high peripheral vascular resistance. Although early and late gestation preeclampsias are considered to be different diseases, we show that the hemodynamic characteristics of preeclampsia were unrelated to gestational age at onset but were strongly associated with the presence or absence of fetal growth restriction. Fetal growth restriction more commonly coexists with preeclampsia at early gestation, thus explaining the conflicting results of previous studies. Furthermore, antihypertensive agents act by reducing cardiac output or peripheral vascular resistance and are administered without reference to cardiovascular function in preeclampsia. The underlying pathology (preeclampsia, fetal growth restriction, preeclampsia and fetal growth restriction) defines cardiovascular phenotype, providing a rational basis for choice of therapy in which high or low cardiac output or peripheral vascular resistance is the predominant feature.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ajog.2018.02.007DOI Listing
May 2018

Sonographic prediction of outcome of vacuum deliveries: a multicenter, prospective cohort study.

Am J Obstet Gynecol 2017 07 19;217(1):69.e1-69.e10. Epub 2017 Mar 19.

National Center for Fetal Medicine, Trondheim University Hospital (St Olav's Hospital) and Department of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology, Trondheim, Norway.

Background: Safe management of the second stage of labor is of great importance. Unnecessary interventions should be avoided and correct timing of interventions should be focused. Ultrasound assessment of fetal position and station has a potential to improve the precision in diagnosing and managing prolonged or arrested labors. The decision to perform vacuum delivery is traditionally based on subjective assessment by digital vaginal examination and clinical expertise and there is currently no method of objectively quantifying the likelihood of successful delivery. Prolonged attempts at vacuum delivery are associated with neonatal morbidity and maternal trauma, especially so if the procedure is unsuccessful and a cesarean is performed.

Objective: The aim of the study was to assess if ultrasound measurements of fetal position and station can predict duration of vacuum extractions, mode of delivery, and fetal outcome in nulliparous women with prolonged second stage of labor.

Study Design: We performed a prospective cohort study in nulliparous women at term with prolonged second stage of labor in 7 European maternity units from 2013 through 2016. Fetal head position and station were determined using transabdominal and transperineal ultrasound, respectively. Our preliminary clinical experience assessing head-perineum distance prior to vacuum delivery suggested that we should set 25 mm for the power calculation, a level corresponding roughly to +2 below the ischial spines. The main outcome was duration of vacuum extraction in relation to ultrasound measured head-perineum distance with a predefined cut-off of 25 mm, and 220 women were needed to discriminate between groups using a hazard ratio of 1.5 with 80% power and alpha 5%. Secondary outcomes were delivery mode and umbilical artery cord blood samples after birth. The time interval was evaluated using survival analyses, and the outcomes of delivery were evaluated using receiver operating characteristic curves and descriptive statistics. Results were analyzed according to intention to treat.

Results: The study population comprised 222 women. The duration of vacuum extraction was shorter in women with head-perineum distance ≤25 mm (log rank test <0.01). The estimated median duration in women with head-perineum distance ≤25 mm was 6.0 (95% confidence interval, 5.2-6.8) minutes vs 8.0 (95% confidence interval, 7.1-8.9) minutes in women with head-perineum distance >25 mm. The head-perineum distance was associated with spontaneous delivery with area under the curve 83% (95% confidence interval, 77-89%) and associated with cesarean with area under the curve 83% (95% confidence interval, 74-92%). In women with head-perineum distance ≤35 mm, 7/181 (3.9%) were delivered by cesarean vs 9/41 (22.0%) in women with head-perineum distance >35 mm (P <.01). Ultrasound-assessed position was occiput anterior in 73%. Only 3/138 (2.2%) fetuses in occiput anterior position and head-perineum distance ≤35 mm vs 6/17 (35.3%) with nonocciput anterior position and head-perineum distance >35 mm were delivered by cesarean. Umbilical cord arterial pH <7.10 occurred in 2/144 (1.4%) women with head-perineum distance ≤35 mm compared to 8/40 (20.0%) with head-perineum distance >35 mm (P < .01).

Conclusion: Ultrasound has the potential to predict labor outcome in women with prolonged second stage of labor. The information obtained could guide whether vacuum delivery should be attempted or if cesarean is preferable, whether senior staff should be in attendance, and if the vacuum attempt should be performed in the operating theater.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ajog.2017.03.009DOI Listing
July 2017

Pre-eclampsia: the Potential of GSNO Reductase Inhibitors.

Curr Hypertens Rep 2017 Mar;19(3):20

Imperial College London, London, UK.

Purpose Of Review: Pre-eclampsia remains a leading worldwide cause of maternal death and of perinatal morbidity. There remains no definitive treatment except delivery of the fetus.

Recent Findings: Recent insights into the cardiovascular changes that are evident prior to, during, and persist after pre-eclampsia have improved understanding of the underlying pathophysiology-disruption of normal endothelial function and decreased nitric oxide bioavailability. S-nitrosoglutathione (GSNO) is an endogenous S-nitrosothiol that acts as a NO pool and, by replenishing or preventing the breakdown of GSNO, endothelial dysfunction can be ameliorated. GSNO reductase inhibitors are a novel class of drug that can increase NO bioavailability. GSNO reductase inhibitors have demonstrated improvement of endothelial dysfunction in animal models, and in vivo human studies have shown them to be well tolerated. GSNOR inhibitors offer a potentially promising option for the management of pre-eclampsia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11906-017-0717-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5340829PMC
March 2017

Quantitative analysis of fetal facial morphology using 3D ultrasound and statistical shape modeling: a feasibility study.

Am J Obstet Gynecol 2017 07 14;217(1):76.e1-76.e8. Epub 2017 Feb 14.

Centre for Fetal Care, Queen Charlotte's and Chelsea Hospital, Imperial College Healthcare National Health Service Trust, London, United Kingdom; Institute of 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 antenatal detection of facial dysmorphism using 3-dimensional ultrasound may raise the suspicion of an underlying genetic condition but infrequently leads to a definitive antenatal diagnosis. Despite advances in array and noninvasive prenatal testing, not all genetic conditions can be ascertained from such testing.

Objectives: The aim of this study was to investigate the feasibility of quantitative assessment of fetal face features using prenatal 3-dimensional ultrasound volumes and statistical shape modeling. STUDY DESIGN: Thirteen normal and 7 abnormal stored 3-dimensional ultrasound fetal face volumes were analyzed, at a median gestation of 29 weeks (25 to 36). The 20 3-dimensional surface meshes generated were aligned and served as input for a statistical shape model, which computed the mean 3-dimensional face shape and 3-dimensional shape variations using principal component analysis.

Results: Ten shape modes explained more than 90% of the total shape variability in the population. While the first mode accounted for overall size differences, the second highlighted shape feature changes from an overall proportionate toward a more asymmetric face shape with a wide prominent forehead and an undersized, posteriorly positioned chin. Analysis of the Mahalanobis distance in principal component analysis shape space suggested differences between normal and abnormal fetuses (median and interquartile range distance values, 7.31 ± 5.54 for the normal group vs 13.27 ± 9.82 for the abnormal group) (P = .056).

Conclusion: This feasibility study demonstrates that objective characterization and quantification of fetal facial morphology is possible from 3-dimensional ultrasound. This technique has the potential to assist in utero diagnosis, particularly of rare conditions in which facial dysmorphology is a feature.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ajog.2017.02.007DOI Listing
July 2017

Early onset fetal growth restriction.

Matern Health Neonatol Perinatol 2017 18;3. Epub 2017 Jan 18.

Centre for Fetal Care, Queen Charlotte's and Chelsea Hospital, Imperial College Healthcare NHS Trust, Du Cane Road, London, W12 0HS United Kingdom.

Fetal growth restriction (FGR) diagnosed before 32 weeks is identified by fetal smallness associated with Doppler abnormalities and is associated with significant perinatal morbidity and mortality and maternal complications. Recent studies have provided new insights into pathophysiology, management options and postnatal outcomes of FGR. In this paper we review the available evidence regarding diagnosis, management and prognosis of fetuses diagnosed with FGR before 32 weeks of gestation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40748-016-0041-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5241928PMC
January 2017

Phase-rectified signal averaging method to predict perinatal outcome in infants with very preterm fetal growth restriction- a secondary analysis of TRUFFLE-trial.

Am J Obstet Gynecol 2016 Nov 23;215(5):630.e1-630.e7. Epub 2016 Jun 23.

Frauenklinik und Poliklinik, Technische Universität München, Munich, Germany.

Background: Phase-rectified signal averaging, an innovative signal processing technique, can be used to investigate quasi-periodic oscillations in noisy, nonstationary signals that are obtained from fetal heart rate. Phase-rectified signal averaging is currently the best method to predict survival after myocardial infarction in adult cardiology. Application of this method to fetal medicine has established significantly better identification than with short-term variation by computerized cardiotocography of growth-restricted fetuses.

Objective: The aim of this study was to determine the longitudinal progression of phase-rectified signal averaging indices in severely growth-restricted human fetuses and the prognostic accuracy of the technique in relation to perinatal and neurologic outcome.

Study Design: Raw data from cardiotocography monitoring of 279 human fetuses were obtained from 8 centers that took part in the multicenter European "TRUFFLE" trial on optimal timing of delivery in fetal growth restriction. Average acceleration and deceleration capacities were calculated by phase-rectified signal averaging to establish progression from 5 days to 1 day before delivery and were compared with short-term variation progression. The receiver operating characteristic curves of average acceleration and deceleration capacities and short-term variation were calculated and compared between techniques for short- and intermediate-term outcome.

Results: Average acceleration and deceleration capacities and short-term variation showed a progressive decrease in their diagnostic indices of fetal health from the first examination 5 days before delivery to 1 day before delivery. However, this decrease was significant 3 days before delivery for average acceleration and deceleration capacities, but 2 days before delivery for short-term variation. Compared with analysis of changes in short-term variation, analysis of (delta) average acceleration and deceleration capacities better predicted values of Apgar scores <7 and antenatal death (area under the curve for prediction of antenatal death: delta average acceleration capacity, 0.62 [confidence interval, 0.19-1.0]; delta short-term variation, 0.54 [confidence interval, 0.13-0.97]; P=.006; area under the curve for prediction Apgar <7: average deceleration capacity <24 hours before delivery, 0.64 [confidence interval, 0.52-0.76]; short-term variation <24 hours before delivery, 0.53 [confidence interval, 0.40-0.65]; P=.015). Neither phase-rectified signal averaging indices nor short-term variation showed predictive power for developmental disability at 2 years of age (Bayley developmental quotient, <95 or <85).

Conclusion: The phase-rectified signal averaging method seems to be at least as good as short-term variation to monitor progressive deterioration of severely growth-restricted fetuses. Our findings suggest that for short-term outcomes such as Apgar score, phase-rectified signal averaging indices could be an even better test than short-term variation. Overall, our findings confirm the possible value of prospective trials based on phase-rectified signal averaging indices of autonomic nervous system of severely growth-restricted fetuses.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ajog.2016.06.024DOI Listing
November 2016

Noninvasive high-intensity focused ultrasound treatment of twin-twin transfusion syndrome: A preliminary in vivo study.

Sci Transl Med 2016 07;8(347):347ra95

Institute of Reproductive and Developmental Biology, Imperial College London, London W12 0HS, UK. Department of Obstetrics and Gynaecology, University Hospitals Leuven, 3000 Leuven, Belgium.

We investigated the efficacy, maternofetal responses, and safety of using high-intensity focused ultrasound (HIFU) for noninvasive occlusion of placental vasculature compared to sham treatment in anesthetized pregnant sheep. This technique for noninvasive occlusion of placental vasculature may be translatable to the treatment of conditions arising from abnormal placental vasculature, such as twin-twin transfusion syndrome (TTTS). Eleven pregnant sheep were instrumented with maternal and fetal arterial catheters and time-transit flow probes to monitor cardiovascular, acid-base, and metabolic status, and then exposed to HIFU (n = 5) or sham (n = 6) ablation of placental vasculature through the exposed uterine surface. Placental vascular flow was occluded in 28 of 30 targets, and histological examination confirmed occlusion in 24 of 30 targets. In both HIFU and sham exposures, uterine contact reduced maternal uterine artery flow, but delivery of oxygen and glucose to the fetal brain remained normal. HIFU can consistently occlude in vivo placental vessels and ablate blood flow in a pregnant sheep model. Cardiovascular and metabolic fetal responses suggest that the technique is safe in the short term and potentially translatable to human pregnancy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1126/scitranslmed.aaf2135DOI Listing
July 2016

Fetal movements as a predictor of health.

Acta Obstet Gynecol Scand 2016 Sep;95(9):968-75

Institute of Reproductive and Developmental Biology, Department of Surgery & Cancer, Imperial College London, London, UK.

The key determinant to a fetus maintaining its health is through adequate perfusion and oxygen transfer mediated by the functioning placenta. When this equilibrium is distorted, a number of physiological changes, including reduced fetal growth, occur to favor survival. Technologies have been developed to monitor these changes with a view to prolong intrauterine maturity while reducing the risks of stillbirth. Many of these strategies involve complex interpretation, for example Doppler ultrasound for fetal blood flow and computerized analysis of fetal heart rate changes. However, even with these modalities of fetal assessment to determine the optimal timing of delivery, fetal movements remain integral to clinical decision-making. In high-risk cohorts with fetal growth restriction, the manifestation of a reduction in perceived movements may warrant an expedited delivery. Despite this, there has been little evolution in the development of technologies to objectively evaluate fetal movement behavior for clinical application. This review explores the available literature on the value of fetal movement analysis as a method of assessing fetal wellbeing, and demonstrates how interdisciplinary developments in this area may aid in the improvement of clinical outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/aogs.12944DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6680271PMC
September 2016

Adjunctive use of intrapartum foetal ST-segment analysis (STAN) confers no benefit over conventional foetal heart rate monitoring.

Evid Based Med 2016 06 16;21(3):105-6. Epub 2016 Mar 16.

Department of Surgery and Cancer, Imperial College London, London, UK Queen Charlotte's and Chelsea Hospitals, Imperial College Healthcare NHS Trust, London and Department of Development and Regeneration, KU Leuven, Belgium.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/ebmed-2015-110304DOI Listing
June 2016

Delivery of the growth-restricted preterm fetus - Author's reply.

Lancet 2015 Oct;386(10001):1336

Department of Surgery and Cancer, Imperial College London, London SW7 2AZ, UK. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S0140-6736(15)00328-1DOI Listing
October 2015

Cerebroplacental ratio in fetal surveillance: an alert bell or a crash sound?

Am J Obstet Gynecol 2016 Feb 8;214(2):297-298. Epub 2015 Oct 8.

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

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ajog.2015.09.097DOI Listing
February 2016

A model to predict vaginal delivery in nulliparous women based on maternal characteristics and intrapartum ultrasound.

Am J Obstet Gynecol 2015 Sep 22;213(3):362.e1-6. Epub 2015 May 22.

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

Objective: Accurate prediction of whether a nulliparous woman will have a vaginal delivery would be a major advance in obstetrics. The objective of the study was to develop such a model based on maternal characteristics and the results of intrapartum ultrasound.

Study Design: One hundred twenty-two nulliparous women in the first stage of labor were included in a prospective observational 2-centre study. Labor was classified as prolonged according to the respective countries' national guidelines. Fetal head position was assessed with transabdominal ultrasound and cervical dilatation by digital examination, and transperineal ultrasound was used to determine head-perineum distance and the presence of caput succedaneum. The subjects were divided into a testing set (n = 61) and a validation set (n = 61) and a risk score derived using multivariable logistic regression with vaginal birth as the outcome, which was dichotomized into no/cesarean delivery and yes/vaginal birth. Covariates included head-perineum distance, caput succedaneum, and occiput posterior position, which were dichotomized respectively into the following: ≤40 mm, >40 mm, <10 mm, ≥10 mm, and no, yes. Maternal age, gestational age, and maternal body mass index were included as continuous covariates.

Results: Dichotomized score is significantly associated with vaginal delivery (P = .03). Women with a score above the median had greater than 10 times the odds of having a vaginal delivery as compared with those with a score below the median. The receiver-operating characteristic curve showed an area under the curve of 0.853 (95% confidence interval, 0.678-1.000).

Conclusion: A risk score based on maternal characteristics and intrapartum findings can predict vaginal delivery in nulliparous women in the first stage of labor.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ajog.2015.05.044DOI Listing
September 2015

2 year neurodevelopmental and intermediate perinatal outcomes in infants with very preterm fetal growth restriction (TRUFFLE): a randomised trial.

Lancet 2015 May 5;385(9983):2162-72. Epub 2015 Mar 5.

Department of Obstetrics and Gynecology, Academic Medical Centre, Amsterdam, Netherlands; Department of Obstetrics and Gynecology, Academic Medical Centre, Amsterdam, Netherlands.

Background: No consensus exists for the best way to monitor and when to trigger delivery in mothers of babies with fetal growth restriction. We aimed to assess whether changes in the fetal ductus venosus Doppler waveform (DV) could be used as indications for delivery instead of cardiotocography short-term variation (STV).

Methods: In this prospective, European multicentre, unblinded, randomised study, we included women with singleton fetuses at 26-32 weeks of gestation who had very preterm fetal growth restriction (ie, low abdominal circumference [<10th percentile] and a high umbilical artery Doppler pulsatility index [>95th percentile]). We randomly allocated women 1:1:1, with randomly sized blocks and stratified by participating centre and gestational age (<29 weeks vs ≥29 weeks), to three timing of delivery plans, which differed according to antenatal monitoring strategies: reduced cardiotocograph fetal heart rate STV (CTG STV), early DV changes (pulsatility index >95th percentile; DV p95), or late DV changes (A wave [the deflection within the venous waveform signifying atrial contraction] at or below baseline; DV no A). The primary outcome was survival without cerebral palsy or neurosensory impairment, or a Bayley III developmental score of less than 85, at 2 years of age. We assessed outcomes in surviving infants with known outcomes at 2 years. We did an intention to treat study for all participants for whom we had data. Safety outcomes were deaths in utero and neonatal deaths and were assessed in all randomly allocated women. This study is registered with ISRCTN, number 56204499.

Findings: Between Jan 1, 2005 and Oct 1, 2010, 503 of 542 eligible women were randomly allocated to monitoring groups (166 to CTG STV, 167 to DV p95, and 170 to DV no A). The median gestational age at delivery was 30·7 weeks (IQR 29·1-32·1) and mean birthweight was 1019 g (SD 322). The proportion of infants surviving without neuroimpairment did not differ between the CTG STV (111 [77%] of 144 infants with known outcome), DV p95 (119 [84%] of 142), and DV no A (133 [85%] of 157) groups (ptrend=0·09). 12 fetuses (2%) died in utero and 27 (6%) neonatal deaths occurred. Of survivors, more infants where women were randomly assigned to delivery according to late ductus changes (133 [95%] of 140, 95%, 95% CI 90-98) were free of neuroimpairment when compared with those randomly assigned to CTG (111 [85%] of 131, 95% CI 78-90; p=0.005), but this was accompanied by a non-significant increase in perinatal and infant mortality.

Interpretation: Although the difference in the proportion of infants surviving without neuroimpairment was non-significant at the primary endpoint, timing of delivery based on the study protocol using late changes in the DV waveform might produce an improvement in developmental outcomes at 2 years of age.

Funding: ZonMw, The Netherlands and Dr Hans Ludwig Geisenhofer Foundation, Germany.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S0140-6736(14)62049-3DOI Listing
May 2015

NICE guidance on place of birth falls short of neutrality.

BMJ 2014 Dec 31;349:g7776. Epub 2014 Dec 31.

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

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmj.g7776DOI Listing
December 2014

S-Nitrosoglutathione improves haemodynamics in early-onset pre-eclampsia.

Br J Clin Pharmacol 2014 Sep;78(3):660-9

Fetal Medicine Department, Rosie Hospital, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 2QQ, UK.

Aims: To determine the effects of in vivo S-nitrosoglutathione (GSNO) infusion on cardiovascular function, platelet function, proteinuria and biomarker parameters in early-onset pre-eclampsia.

Methods: We performed an open-label dose-ranging study of GSNO in early-onset pre-eclampsia. Six women underwent GSNO infusion whilst receiving standard therapy. The dose of GSNO was increased incrementally to 100 μg min(-1) whilst maintaining blood pressure of >140/80 mmHg. Aortic augmentation index, aortic pulse wave velocity, blood pressure and maternal-fetal Doppler parameters were measured at each dose. Platelet P-selectin, protein-to-creatinine ratio and soluble anti-angiogenic factors were measured pre- and postinfusion.

Results: Augmentation index fell at 30 μg min(-1) S-nitrosoglutathione (-6%, 95% confidence interval 0.6 to 13%), a dose that did not affect blood pressure. Platelet P-selectin expression was reduced [mean (interquartile range), 6.3 (4.9-7.6) vs. 4.1 (3.1-5.7)% positive, P = 0.03]. Soluble endoglin levels showed borderline reduction (P = 0.06). There was a borderline significant change in pre-to-postinfusion protein-to-creatinine ratio [mean (interquartile range), 0.37 (0.09-0.82) vs. 0.23 (0.07-0.49) g mmol(-1) , P = 0.06]. Maternal uterine and fetal Doppler pulsatility indices were unchanged.

Conclusions: In early-onset pre-eclampsia, GSNO reduces augmentation index, a biomarker of small vessel tone and pulse wave reflection, prior to affecting blood pressure. Proteinuria and platelet activation are improved at doses that affect blood pressure minimally. These effects of GSNO may be of therapeutic potential in pre-eclampsia, a condition for which no specific treatment exists. Clinical studies of GSNO in early-onset pre-eclampsia will determine whether these findings translate to improvement in maternal and/or fetal outcome.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/bcp.12379DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4243916PMC
September 2014