Publications by authors named "Hatem A Mousa"

22 Publications

  • Page 1 of 1

Effect of metformin on biomarkers of placental- mediated disease: A systematic review and meta-analysis.

Placenta 2021 Mar 9;107:51-58. Epub 2021 Mar 9.

University Hospitals of Leicester NHS Trust, Leicester, UK.

Metformin reduces the incidence of placental-mediated disease (PMD) in pregnancies with and without diabetes, but the mechanism through which it exerts these effects is not yet fully understood. We performed a systematic review and meta-analysis to examine the effect of metformin on biomarkers implicated in the pathogenesis of PMD. We searched Medline, Embase and the Cochrane Library for studies of metformin and biomarkers of PMD in pregnancy. Meta-analysis was undertaken where comparable data were obtained from two or more studies. 12 studies were included in the final review. Meta-analysis of 2 studies including 323 pregnant women showed significantly reduced CRP levels following treatment with metformin compared to placebo [mean difference = -1.72, 95% CI (-2.97; -0.48); p = 0.007]. Metformin exposure was also associated with decreased levels of the inflammatory cytokines TNFα, IL-1a, IL-1b and IL-6 in serum, placenta and omental tissue taken from pregnant women. Metformin significantly decreased the release of anti-angiogenic factors sFlt-1 and sEng from ex-vivo placental and umbilical vein tissue, and increased maternal serum levels of non-phosphorylated IGFBP-1. Overall, our findings show that metformin mediates several molecular pathways implicated in the pathogenesis of pre-eclampsia and intrauterine growth retardation. Metformin therefore has exciting potential as a therapeutic, as well as preventative, agent in the treatment of PMD, which warrants further investigation.
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http://dx.doi.org/10.1016/j.placenta.2021.02.021DOI Listing
March 2021

Noninvasive prenatal screening in twin pregnancies with cell-free DNA using the IONA test: a prospective multicenter study.

Am J Obstet Gynecol 2021 Jan 15. Epub 2021 Jan 15.

Fetal Medicine Unit, Department of Obstetrics and Gynaecology, and Twins Trust Centre for Research and Clinical Excellence, St George's University Hospitals NHS Foundation Trust, London, United Kingdom; Nuffield Department of Women's and Reproductive Health, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.

Background: In singleton pregnancies, studies investigating cell-free DNA in maternal blood have consistently reported high detection rate and low false-positive rate for the 3 common fetal trisomies (trisomies 21, 18, and 13). The potential advantages of noninvasive prenatal testing in twin pregnancies are even greater than in singletons, in particular lower need for invasive testing and consequent fetal loss rate. However, several organizations do not recommend cell-free DNA in twin pregnancies and call for larger prospective studies.

Objective: In response to this, we undertook a large prospective multicenter study to establish the screening performance of cell-free DNA for the 3 common trisomies in twin pregnancies. Moreover, we combined our data with that reported in published studies to obtain the best estimate of screening performance.

Study Design: This was a prospective multicenter blinded study evaluating the screening performance of cell-free DNA in maternal plasma for the detection of fetal trisomies in twin pregnancies. The study took place in 6 fetal medicine centers in England, United Kingdom. The primary outcome was the screening performance and test failure rate of cell-free DNA using next generation sequencing (the IONA test). Maternal blood was taken at the time of (or after) a conventional screening test. Data were collected at enrolment, at any relevant invasive testing throughout pregnancy, and after delivery until the time of hospital discharge. Prospective detailed outcome ascertainment was undertaken on all newborns. The study was undertaken and reported according to the Standards for Reporting of Diagnostic Accuracy Studies. A pooled analysis was also undertaken using our data and those in the studies identified by a literature search (MEDLINE, Embase, CENTRAL, Cochrane Library, and ClinicalTrials.gov) on June 6, 2020.

Results: A total of 1003 women with twin pregnancies were recruited, and complete data with follow-up and reference data were available for 961 (95.8%); 276 were monochorionic and 685 were dichorionic. The failure rate was 0.31%. The mean fetal fraction was 12.2% (range, 3%-36%); all 9 samples with a 3% fetal fraction provided a valid result. There were no false-positive or false-negative results for trisomy 21 or trisomy 13, whereas there was 1 false-negative and 1 false-positive result for trisomy 18. The IONA test had a detection rate of 100% for trisomy 21 (n=13; 95% confidence interval, 75-100), 0% for trisomy 18 (n=1; 95% confidence interval, 0-98), and 100% for trisomy 13 (n=1; 95% confidence interval, 3-100). The corresponding false-positive rates were 0% (95% confidence interval, 0-0.39), 0.10% (95% confidence interval, 0-0.58), and 0% (95% confidence interval, 0-0.39), respectively. By combining data from our study with the 11 studies identified by literature search, the detection rate for trisomy 21 was 95% (n=74; 95% confidence interval, 90-99) and the false-positive rate was 0.09% (n=5598; 95% confidence interval, 0.03-0.19). The corresponding values for trisomy 18 were 82% (n=22; 95% confidence interval, 66-93) and 0.08% (n=4869; 95% confidence interval, 0.02-0.18), respectively. There were 5 cases of trisomy 13 and 3881 non-trisomy 13 pregnancies, resulting in a computed average detection rate of 80% and a false-positive rate of 0.13%.

Conclusion: This large multicenter study confirms that cell-free DNA testing is the most accurate screening test for trisomy 21 in twin pregnancies, with screening performance similar to that in singletons and very low failure rates (0.31%). The predictive accuracy for trisomies 18 and 13 may be less. However, given the low false-positive rate, offering first-line screening with cell-free DNA to women with twin pregnancy is appropriate in our view and should be considered a primary screening test for trisomy 21 in twins.
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http://dx.doi.org/10.1016/j.ajog.2021.01.005DOI Listing
January 2021

Mechanical and surgical interventions for treating primary postpartum haemorrhage.

Cochrane Database Syst Rev 2020 07 1;7:CD013663. Epub 2020 Jul 1.

Department of Women's and Children's Health, The University of Liverpool, Liverpool, UK.

Background: Primary postpartum haemorrhage (PPH) is commonly defined as bleeding from the genital tract of 500 mL or more within 24 hours of birth. It is one of the most common causes of maternal mortality worldwide and causes significant physical and psychological morbidity. An earlier Cochrane Review considering any treatments for the management of primary PPH, has been split into separate reviews. This review considers treatment with mechanical and surgical interventions.

Objectives: To determine the effectiveness and safety of mechanical and surgical interventions used for the treatment of primary PPH.

Search Methods: We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (26 July 2019) and reference lists of retrieved studies.

Selection Criteria: Randomised controlled trials (RCTs) of mechanical/surgical methods for the treatment of primary PPH compared with standard care or another mechanical/surgical method. Interventions could include uterine packing, intrauterine balloon insertion, artery ligation/embolism, or uterine compression (either with sutures or manually). We included studies reported in abstract form if there was sufficient information to permit risk of bias assessment. Trials using a cluster-RCT design were eligible for inclusion, but quasi-RCTs or cross-over studies were not.

Data Collection And Analysis: Two review authors independently assessed studies for inclusion and risk of bias, independently extracted data and checked data for accuracy. We used GRADE to assess the certainty of the evidence.

Main Results: We included nine small trials (944 women) conducted in Pakistan, Turkey, Thailand, Egypt (four trials), Saudi Arabia, Benin and Mali. Overall, included trials were at an unclear risk of bias. Due to substantial differences between the studies, it was not possible to combine any trials in meta-analysis. Many of this review's important outcomes were not reported. GRADE assessments ranged from very low to low, with the majority of outcome results rated as very low certainty. Downgrading decisions were mainly based on study design limitations and imprecision; one study was also downgraded for indirectness. External uterine compression versus normal care (1 trial, 64 women) Very low-certainty evidence means that we are unclear about the effect on blood transfusion (risk ratio (RR) 2.33, 95% confidence interval (CI) 0.66 to 8.23). Uterine arterial embolisation versus surgical devascularisation plus B-Lynch (1 trial, 23 women) The available evidence for hysterectomy to control bleeding (RR 0.73, 95% CI 0.15 to 3.57) is unclear due to very low-certainty evidence. The available evidence for intervention side effects is also unclear because the evidence was very low certainty (RR 1.09; 95% CI 0.08 to 15.41). Intrauterine Tamponade Studies included various methods of intrauterine tamponade: the commercial Bakri balloon, a fluid-filled condom-loaded latex catheter ('condom catheter'), an air-filled latex balloon-loaded catheter ('latex balloon catheter'), or traditional packing with gauze. Balloon tamponade versus normal care (2 trials, 356 women) One study(116 women) used the condom catheter. This study found that it may increase blood loss of 1000 mL or more (RR 1.52, 95% CI 1.15 to 2.00; 113 women), very low-certainty evidence. For other outcomes the results are unclear and graded as very low-certainty evidence: mortality due to bleeding (RR 6.21, 95% CI 0.77 to 49.98); hysterectomy to control bleeding (RR 4.14, 95% CI 0.48 to 35.93); total blood transfusion (RR 1.49, 95% CI 0.88 to 2.51); and side effects. A second study of 240 women used the latex balloon catheter together with cervical cerclage. Very low-certainty evidence means we are unclear about the effect on hysterectomy (RR 0.14, 95% CI 0.01 to 2.74) and additional surgical interventions to control bleeding (RR 0.20, 95% CI 0.01 to 4.12). Bakri balloon tamponade versus haemostatic square suturing of the uterus (1 trial, 13 women) In this small trial there was no mortality due to bleeding, serious maternal morbidity or side effects of the intervention, and the results are unclear for blood transfusion (RR 0.57, 95% CI 0.14 to 2.36; very low certainty). Bakri balloon tamponade may reduce mean 'intraoperative' blood loss (mean difference (MD) -426 mL, 95% CI -631.28 to -220.72), very low-certainty evidence. Comparison of intrauterine tamponade methods (3 trials, 328 women) One study (66 women) compared the Bakri balloon and the condom catheter, but it was uncertain whether the Bakri balloon reduces the risk of hysterectomy to control bleeding due to very low-certainty evidence (RR 0.50, 95% CI 0.05 to 5.25). Very low-certainty evidence also means we are unclear about the results for the risk of blood transfusion (RR 0.97, 95% CI 0.88 to 1.06). A second study (50 women) compared Bakri balloon, with and without a traction stitch. Very low-certainty evidence means we are unclear about the results for hysterectomy to control bleeding (RR 0.20, 95% CI 0.01 to 3.97). A third study (212 women) compared the condom catheter to gauze packing and found that it may reduce fever (RR 0.47, 95% CI 0.38 to 0.59), but again the evidence was very low certainty. Modified B-Lynch compression suture versus standard B-Lynch compression suture (1 trial, 160 women) Low-certainty evidence suggests that a modified B-Lynch compression suture may reduce the risk of hysterectomy to control bleeding (RR 0.33, 95% CI 0.11 to 0.99) and postoperative blood loss (MD -244.00 mL, 95% CI -295.25 to -192.75).

Authors' Conclusions: There is currently insufficient evidence from RCTs to determine the relative effectiveness and safety of mechanical and surgical interventions for treating primary PPH. High-quality randomised trials are urgently needed, and new emergency consent pathways should facilitate recruitment. The finding that intrauterine tamponade may increase total blood loss > 1000 mL suggests that introducing condom-balloon tamponade into low-resource settings on its own without multi-system quality improvement does not reduce PPH deaths or morbidity. The suggestion that modified B-Lynch suture may be superior to the original requires further research before the revised technique is adopted. In high-resource settings, uterine artery embolisation has become popular as the equipment and skills become more widely available. However, there is little randomised trial evidence regarding efficacy and this requires further research. We urge new trial authors to adopt PPH core outcomes to facilitate consistency between primary studies and subsequent meta-analysis.
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http://dx.doi.org/10.1002/14651858.CD013663DOI Listing
July 2020

Antifibrinolytic drugs for treating primary postpartum hemorrhage.

Emergencias 2020 06;32(3):203-205

University Department of Obstetrics and Gynaecology, Fetal and Maternal Medicine Unit, Leicester Royal Infirmary, Leicester, Reino Unido.

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June 2020

An integrated in utero MR method for assessing structural brain abnormalities and measuring intracranial volumes in fetuses with congenital heart disease: results of a prospective case-control feasibility study.

Neuroradiology 2019 May 22;61(5):603-611. Epub 2019 Feb 22.

Academic Unit of Radiology, University of Sheffield, Floor C, Royal Hallamshire Hospital, Glossop Road, Sheffield, S10 2JF, UK.

Purpose: To refine methods that assess structural brain abnormalities and calculate intracranial volumes in fetuses with congenital heart diseases (CHD) using in utero MR (iuMR) imaging. Our secondary objective was to assess the prevalence of brain abnormalities in this high-risk cohort and compare the brain volumes with normative values.

Methods: We performed iuMR on 16 pregnant women carrying a fetus with CHD and gestational age ≥ 28-week gestation and no brain abnormality on ultrasonography. All cases had fetal echocardiography by a pediatric cardiologist. Structural brain abnormalities on iuMR were recorded. Intracranial volumes were made from 3D FIESTA acquisitions following manual segmentation and the use of 3D Slicer software and were compared with normal fetuses. Z scores were calculated, and regression analyses were performed to look for differences between the normal and CHD fetuses.

Results: Successful 2D and 3D volume imaging was obtained in all 16 cases within a 30-min scan. Despite normal ultrasonography, 5/16 fetuses (31%) had structural brain abnormalities detected by iuMR (3 with ventriculomegaly, 2 with vermian hypoplasia). Brain volume, extra-axial volume, and total intracranial volume were statistically significantly reduced, while ventricular volumes were increased in the CHD cohort.

Conclusion: We have shown that it is possible to perform detailed 2D and 3D studies using iuMR that allow thorough investigation of all intracranial compartments in fetuses with CHD in a clinically appropriate scan time. Those fetuses have a high risk of structural brain abnormalities and smaller brain volumes even when brain ultrasonography is normal.
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http://dx.doi.org/10.1007/s00234-019-02184-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6477996PMC
May 2019

Haemodynamic differences amongst women who were screened for gestational diabetes in comparison to healthy controls.

Pregnancy Hypertens 2018 Oct 27;14:23-28. Epub 2018 Jul 27.

Consultant/Honorary Senior Lecturer in Maternal and Fetal Medicine, University of Leicester, United Kingdom. Electronic address:

Aim: To assess the changes in haemodynamics amongst pregnant women who were screened for gestational diabetes mellitus (GDM) in comparison to low-risk healthy pregnant controls.

Methodology: A total of 120 pregnant women of mean (standard deviation) age 31.03 (5.41) years who attended their oral glucose tolerance test as part of the national screening for GDM (study), and 60 low-risk healthy pregnant women (control) of mean age 29.71 (5.33) years, were invited to participate in this study. All women included in the study booked at the University Hospitals of Leicester NHS Trust and fulfilled the relevant inclusion criteria. Non-invasive assessment of arterial stiffness and cardiac output were undertaken on participants between 26 and 28 weeks of pregnancy. The mean difference between GDM and low-risk group for each of the arterial stiffness and cardiac output measurements was assessed by a two-sample unpaired t-test.

Results: Significant differences were found between the study and control groups for brachial (-64.5 vs. -69.5, p < 0.04) and aortic augmentation indices (5.2 vs. 2.7, p = 0.04), though there was no significant difference for PWV (8.3 vs. 8.1, p = 0.49). Cardiac output (7.6 vs. 7.0, p = 0.011), stroke volume (84.4 vs. 76.9, p = 0.013) and central mean arterial pressure (71 vs. 58, <0.001) were also significantly different between groups. However, no significant differences were reported for heart rate, systolic and diastolic blood pressure, or total peripheral resistance.

Conclusion: Pregnant women at risk of GDM between gestational weeks 26 and 28 had significantly increased measures of arterial stiffness, as assessed by brachial and aortic augmentation indices, compared with low-risk healthy controls. Whether these women are at greater long-term cardiovascular disease risk warrants further investigation.
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http://dx.doi.org/10.1016/j.preghy.2018.07.007DOI Listing
October 2018

The effects of metformin on maternal haemodynamics in gestational diabetes mellitus: A pilot study.

Diabetes Res Clin Pract 2018 May 7;139:170-178. Epub 2018 Mar 7.

University of Leicester, UK. Electronic address:

Background: Gestational diabetes mellitus (GDM) is a major clinical challenge and is likely to remain so as the incidence of GDM continues to increase.

Aim: To assess longitudinal changes in maternal haemodynamics amongst women diagnosed with GDM requiring either metformin or dietary intervention in comparison to low-risk healthy controls.

Methodology: Fifty-six pregnant women attending their first appointment at the GDM clinic and 60 low-risk healthy pregnant controls attending their routine antenatal clinics were recruited and assigned to three groups: GDM Metformin (GDM-M), GDM Diet (GDM-D) and Control. Non-invasive assessment of maternal haemodynamics, using recognised measures of arterial stiffness and central blood pressure (Arteriograph®), were undertaken under controlled conditions within four gestational windows: antenatal; AN1 (26-28 weeks), AN2 (32-34 weeks) and AN3 (37-40 weeks), and postnatal (PN) (6-8 weeks after delivery). Data were analysed using a linear mixed model incorporating gestational age and other relevant predictors, including age, blood pressure (BP), baseline bodyweight and pulse as fixed effects, and patient as a random effect.

Results: Fitted linear mixed models showed evidence of a two-way interaction effect between groups (GDM-D, GDM-M and Control) and stages of gestation (AN1, AN2, AN3 and PN) for maternal haemodynamic parameters: brachial artery augmentation index (AIx) (p = 0.004), aortic AIx (p = 0.008), and central systolic BP (p = 0.001). However, differences in respect of aortic pulse wave velocity (p = 0.001) and heart rate (p < 0.001) were only significant for gestational stage. At AN2, we did not observe any evidence that the mean brachial Aix in the GDM-M was different from the control group (p = 0.158).

Conclusion: AIx and central systolic BP measures of arterial stiffness are adversely affected by GDM in comparison to controls during pregnancy. The possible beneficial effects of metformin therapy seen at 32 to 34 weeks of gestation require further exploration.
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http://dx.doi.org/10.1016/j.diabres.2018.03.003DOI Listing
May 2018

Antifibrinolytic drugs for treating primary postpartum haemorrhage.

Cochrane Database Syst Rev 2018 02 20;2:CD012964. Epub 2018 Feb 20.

Clinical Trials Unit, London School of Hygiene & Tropical Medicine, Keppel Street, London, UK, WC1E 7HT.

Background: Postpartum haemorrhage (PPH) - heaving bleeding within the first 24 hours after giving birth - is one of the main causes of death of women after childbirth. Antifibrinolytics, primarily tranexamic acid (TXA), have been shown to reduce bleeding in surgery and safely reduces mortality in trauma patients with bleeding without increasing the risk of adverse events.An earlier Cochrane review on treatments for primary PPH covered all the various available treatments - that review has now been split by types of treatment. This new review concentrates only on the use of antifibrinolytic drugs for treating primary PPH.

Objectives: To determine the effectiveness and safety of antifibrinolytic drugs for treating primary PPH.

Search Methods: We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (28 May 2017) and reference lists of retrieved studies.

Selection Criteria: Randomised controlled trials (RCTs), including cluster-randomised trials of antifibrinolytic drugs (aprotinin, TXA, epsilon-aminocaproic acid (EACA) and aminomethylbenzoic acid, administered by whatever route) for primary PPH in women.Participants in the trials were women after birth following a pregnancy of at least 24 weeks' gestation with a diagnosis of PPH, regardless of mode of birth (vaginal or caesarean section) or other aspects of third stage management.We have not included quasi-randomised trials, or cross-over studies. Studies reported as abstracts have not been included if there was insufficient information to allow assessment of risk of bias.In this review we only identified studies looking at TXA.

Data Collection And Analysis: Two review authors independently extracted data from each study using an agreed form. We entered data into Review Manager software and checked for accuracy.For key review outcomes, we rated the quality of the evidence as 'high', 'moderate', 'low' or 'very low' according to the GRADE approach.

Main Results: Three trials (20,412 women) met our inclusion criteria. Two trials (20,212 women) compared intravenous (IV) TXA with placebo or standard care and were conducted in acute hospital settings (labour ward, emergency department) (in high-, middle- and low-income countries).One other trial (involving 200 women) was conducted in Iran and compared IV TXA with rectal misoprostol, but did not report on any of this review's primary or GRADE outcomes. There were no trials that assessed EACA, aprotinin or aminomethylbenzoic acid.Standard care plus IV TXA for the treatment of primary PPH compared with placebo or standard care aloneTwo trials (20,212 women) assessed the effect of TXA for the treatment of primary PPH compared with placebo or standard care alone. The larger of these (The WOMAN trial) contributed over 99% of the data and was assessed as being at low risk of bias. The quality of the evidence varied for different outcomes, Overall, evidence was mainly graded as moderate to high quality.The data show that IV TXA reduces the risk of maternal death due to bleeding (risk ratio (RR) 0.81, 95% confidence interval (CI) 0.65 to 1.00; two trials, 20,172 women; quality of evidence: moderate). The quality of evidence was rated as moderate due to imprecision of effect estimate. The effect was more evident in women given treatment between one and three hours after giving birth with no apparent reduction when given after three hours (< one hour = RR 0.80, 95% CI 0.55 to 1.16; one to three hours = RR 0.60, 95% CI 0.41 to 0.88; > three hours = RR 1.07, 95% 0.76 to 1.51; test for subgroup differences: Chi² = 4.90, df = 2 (P = 0.09), I² = 59.2%). There was no heterogeneity in the effect by mode of birth (test for subgroup differences: Chi² = 0.01, df = 1 (P = 0.91), I² = 0%). There were fewer deaths from all causes in women receiving TXA, although the 95% CI for the effect estimate crosses the line of no effect (RR 0.88, 95% CI 0.74 to 1.05; two trials, 20,172 women, quality of evidence: moderate). Results from one trial with 151 women suggest that blood loss of ≥ 500 mL after randomisation may be reduced (RR 0.50, 95% CI 0.27 to 0.93; one trial, 151 women; quality of evidence: low). TXA did not reduce the risk of serious maternal morbidity (RR 0.99, 95% CI 0.83 to 1.19; one trial, 20,015 women; quality of evidence: high), hysterectomy to control bleeding (RR 0.95, 95% CI 0.81 to 1.12; one trial, 20,017 women; quality of evidence: high) receipt of blood transfusion (any) (RR 1.00, 95% CI 0.97 to 1.03; two trials, 20,167 women; quality of evidence: moderate) or maternal vascular occlusive events (any), although results were imprecise for this latter outcome (RR 0.88, 95% CI 0.54 to 1.43; one trial, 20,018 women; quality of evidence: moderate). There was an increase in the use of brace sutures in the TXA group (RR 1.19, 95% CI 1.01, 1.41) and a reduction in the need for laparotomy for bleeding (RR 0.64, 95% CI 0.49, 0.85).

Authors' Conclusions: TXA when administered intravenously reduces mortality due to bleeding in women with primary PPH, irrespective of mode of birth, and without increasing the risk of thromboembolic events. Taken together with the reliable evidence of the effect of TXA in trauma patients, the evidence suggests that TXA is effective if given as early as possible.Facilities for IV administration may not be available in non-hospital settings therefore, alternative routes to IV administration need to be investigated.
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http://dx.doi.org/10.1002/14651858.CD012964DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6491317PMC
February 2018

Association between arterial stiffness and wave reflection with subsequent development of placental-mediated diseases during pregnancy: findings of a systematic review and meta-analysis.

J Hypertens 2018 05;36(5):1005-1014

Department of Maternal and Fetal Medicine, University Hospitals of Leicester, Leicester.

Objective: We present a comprehensive systematic review of published literature to examine, whether arterial stiffness and wave reflection measurements during pregnancy differed between healthy patients and patients with placental-mediated diseases including preeclampsia (PET), small for gestational age (SGA), fetal death, and placental abruption, and a quantitative assessment of the findings using the meta-analysis approach.

Methods: We searched Medline, Embase, and The Cochrane Library for studies of arterial stiffness in pregnancy, analyzed pregnancy outcomes and conducted the meta-analysis of data evaluated by trimesters of pregnancy. Hemodynamic parameters evaluated included: pulse wave velocity (PWV), augmentation index (AIx), and augmentation index-75 (AIx-75).

Results: We screened 2806 citations, reviewed 36 studies and included nine (n = 15 923) studies for further quantitative assessment. Compared with healthy pregnancy, measures of arterial stiffness and wave reflection were consistently increased among pregnant women who subsequently developed PET during all trimesters. In the first trimester, mean AIx-75 (%) in the PET group was significantly higher with estimated standardized mean difference (SMD) of 0.90 [95% confidence intervals (95% CI) 0.07-1.73; P = 0.034]. In the second trimester, the PET group had significantly higher PWV (m/s) with estimated SMD of 1.26 (95% CI 0.22-2.30; P = 0.018). Concerning the SGA group, mean AIx (%) was greater during the second trimester only: 65.5 (SD 15.6) vs. 57.0 (11.2), P < 0.01.

Conclusion: There is significant increase in arterial stiffness and wave reflection parameters among pregnant women who subsequently developed PET and SGA fetuses. Larger studies with consistent methodological designs are required to evaluate the role and usefulness of arterial stiffness and wave reflection measurements as a screening tool for placental-mediated diseases during pregnancy.
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http://dx.doi.org/10.1097/HJH.0000000000001664DOI Listing
May 2018

Longitudinal study to assess changes in arterial stiffness and cardiac output parameters among low-risk pregnant women.

Pregnancy Hypertens 2017 Oct 16;10:256-261. Epub 2017 Oct 16.

University Hospitals of Leicester, United Kingdom; University of Leicester, United Kingdom. Electronic address:

Aim: A single-centre, prospective longitudinal study to assess changes in maternal arterial stiffness and cardiac output parameters among low-risk healthy pregnant women.

Methodology: Thirty low-risk, healthy, pregnant women attending their routine antenatal dating ultrasound scan were recruited. Non-invasive assessment of arterial stiffness and cardiac output was undertaken at five gestational windows from 11 to 40 weeks of pregnancy. Data were analysed using a linear mixed model incorporating time and other relevant predictors as fixed effects, and patient as a random effect.

Results: Gestational age had a significant effect on all arterial stiffness parameters, including brachial augmentation index (AIx) (p = .001), aortic AIx (p = .002) and aortic pulse wave velocity (p = .002). The aortic AIx (%) reduced during pregnancy: the lowest mean (standard error, SE) was 4.07 (1.01) at 28 weeks before it increased to 7.04 (SE 1.64) at 40 weeks. Similarly, non-invasive assessments of cardiac output (p < .001), stroke volume (p = .014), heart rate (p < .001) and total peripheral resistance (p < .001) demonstrated significant changes with gestational age. Mean cardiac output (l/m) increased during pregnancy reaching a peak at 28 weeks gestation 6.66 (SE 0.28), but dropped thereafter to reach 5.71 (SE 0.25) around term.

Conclusion: The current study provides pregnancy normograms for gestational changes in arterial stiffness and cardiac output parameters among low-risk, healthy pregnant women. Further work will be required to assess the risk of placental mediated diseases and pregnancy outcome among pregnant women with parameters outside the normal range.
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http://dx.doi.org/10.1016/j.preghy.2017.10.007DOI Listing
October 2017

Diurnal variation and repeatability of arterial stiffness and cardiac output measurements in the third trimester of uncomplicated pregnancy.

J Hypertens 2017 12;35(12):2436-2442

aUniversity Hospitals of Leicester bDepartment of Obstetrics and Gynaecology, Health Sciences Division, University of Leicester, Leicester cDepartment of Cardiovascular Sciences and NIHR Leicester Biomedical Research Centre, University of Leicester, Leicester dSt George's University of London, and St Georges University Hospitals NHS Foundation Trust. Molecular and Clinical Sciences Research Institute, London eDiabetes Research Centre and NIHR Leicester Biomedical Research Centre, University of Leicester, Leicester, UK.

Aim: To investigate same day repeated measures and diurnal variation of arterial stiffness, cardiac output (CO), stroke volume (SV) and total peripheral resistance (TPR) during the third trimester of normal pregnancy.

Methodology: Pulse wave velocity (PWV) and augmentation index (AIx) were recorded using the Arteriograph, while CO, SV and TPR were recorded using noninvasive cardiac output monitoring. The measurements were obtained in the third trimester of pregnancy from 21 healthy pregnant women at four time points (morning, afternoon, evening and midnight) over a 24-h period. Triplicate measurements of 67 women were obtained at 5-min intervals to assess repeatability between measurements within a patient.

Results: Diurnal measurements of arterial stiffness for brachial AIx, aortic AIx and PWV were not statistically significantly different at any of the four time points. Estimated means (SD) for PWV at the four stated time points were 7.81 (2.05), 8.45 (1.68), 7.87 (1.74) and 7.64 m/s (1.15), respectively (P = 0.267). Estimates for AIx at those time points were 10.22 (15.62), 4.44 (10.07), 6.49 (10.92) and 8.40% (8.16), respectively (P = 0.295). Similarly, mean arterial pressure, SV, SV index and TPR did not show any evidence of diurnal variation. However, we observed that the mean CO, cardiac index (CI) and heart rate (HR) varied from morning to midnight; the mean CO, HR and CI increased significantly in the afternoon compared with the corresponding mean morning measurements in a similar fashion to HR. Mean (SD) CO estimates at the four stated time points were 5.90 (1.33), 6.38 (1.49), 6.18 (1.43) and 5.80 ml/min (1.19), respectively, (P < 0.001), whereas mean CI estimates were 3.65 (0.58), 3.93 (0.68), 3.81 (0.65), and 3.57 (0.48), respectively, (P < 0.001), and mean HR estimates were 95 (12), 98 (13), 95 (12) and 88 (12.98), respectively (P < 0.001). Triplicate measurements of 61 women in our repeatability study showed moderate-to-high correlation between observations on the same woman for all Arteriograph and noninvasive cardiac output monitoring variables (estimates of intraclass correlation ranged from 0.49 to 0.91).

Conclusion: With the exception of CO, CI and HR which showed a diurnal variation, measurements of most haemodynamic parameters did not change significantly from morning to midnight, suggesting there was no evidence of systematic differences in the mean values of these variables at these time points. Multiple consecutive noninvasive measurements of vascular stiffness, CO, SV and TPR were highly correlated confirming repeatability of measurements in the third trimester of uncomplicated pregnancy, so these haemodynamic measurements do not need to be undertaken at a specific time period of the day.
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http://dx.doi.org/10.1097/HJH.0000000000001482DOI Listing
December 2017

Renal anomalies and lymphedema distichiasis syndrome. A rare association?

Am J Med Genet A 2017 Aug 23;173(8):2251-2256. Epub 2017 May 23.

Department of Clinical Genetics, University Hospitals Leicester NHS Trust, Leicester, United Kingdom.

Lymphedema distichiasis syndrome (LDS) is a rare, autosomal dominant genetic condition, characterized by lower limb lymphedema and distichiasis. Other associated features that have been reported include varicose veins, cleft palate, congenital heart defects, and ptosis. We update a previously reported family with a pathogenic variant in FOXC2 (c.412-413insT) where five affected individuals from the youngest generation had congenital renal anomalies detected on prenatal ultrasound scan. These included four fetuses with hydronephrosis and one with bilateral renal agenesis. A further child with LDS had prominence of the left renal pelvis on postnatal renal ultrasound. We also describe a second family in whom the proband and his affected son had congenital renal anomalies; left ectopic kidney, right duplex kidney, and bilateral duplex collecting systems with partial duplex kidney with mild degree of malrotation, respectively. Foxc2 is expressed in the developing kidney and therefore congenital renal anomalies may well be associated, potentially as a low penetrance feature. We propose that all individuals diagnosed with LDS should have a baseline renal ultrasound scan at diagnosis. It would also be important to consider the possibility of renal anomalies during prenatal ultrasound of at risk pregnancies, and that the presence of hydronephrosis may be an indication that the baby is affected with LDS.
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http://dx.doi.org/10.1002/ajmg.a.38293DOI Listing
August 2017

Should we offer prenatal testing for 17q12 microdeletion syndrome to all cases with prenatally diagnosed echogenic kidneys? Prenatal findings in two families with 17q12 microdeletion syndrome and review of the literature.

Prenat Diagn 2015 Dec 9;35(13):1336-41. Epub 2015 Nov 9.

Clinical Genetics Department, University Hospitals Leicester NHS Trust, Leicester, UK.

Objective: The objective of this study is to report the prenatal ultrasound scan findings in four fetuses from two families postnatally diagnosed with 17q12 microdeletion syndrome on microarray CGH and review the literature.

Methods: We report two families presenting with prenatally detected hyperechogenic kidneys. In family 1, the mother had three pregnancies complicated by anhydramnios with bilateral hyperechogenic kidneys, hyperechogenic enlarged cystic kidneys, and bilateral hyperechogenic kidneys with polyhydramnios respectively. In family 2, prenatal ultrasound scans detected hyperechogenic kidneys. A pubmed search for all reported cases of 17q12 deletion between 2005 and 2015 was performed. All publications were reviewed, and findings summarised.

Results: Fourteen publications were deemed suitable for literature review; there was a diagnosis of 17q12 deletion with documented prenatal findings in 25 cases. Prenatal renal anomalies were reported in 88% of these cases. Anomalies were documented from 15 weeks, and most common presentation was hyperechogenic, muticystic, or enlarged kidneys. Both oligohydramnios and polyhydramnios were seen. Postnatal renal ultrasound scan findings were of muticystic or multicystic dysplastic kidney. There did not appear to be correlation of prenatal presentation and severity of renal disease.

Conclusion: Prenatal testing should be offered to all cases of hyperechogenic kidneys, with unknown cause.
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http://dx.doi.org/10.1002/pd.4701DOI Listing
December 2015

Planned home versus hospital care for preterm prelabour rupture of the membranes (PPROM) prior to 37 weeks' gestation.

Cochrane Database Syst Rev 2014 Apr 14(4):CD008053. Epub 2014 Apr 14.

Department of Obstetrics and Gynaecology, Queen's Medical Centre, Nottingham University Hospital, Derby Road, Nottingham, Nottinghamshire, UK, NG7 2UH.

Background: Preterm prelabour rupture of membranes (PPROM) is associated with increased risk of maternal and neonatal morbidity and mortality. Women with PPROM have been predominantly managed in hospital. It is possible that selected women could be managed at home after a period of observation. The safety, cost and women's views about home management have not been established.

Objectives: To assess the safety, cost and women's views about planned home versus hospital care for women with PPROM.

Search Methods: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 July 2013) and the reference lists of all the identified articles.

Selection Criteria: Randomised and quasi-randomised trials comparing planned home versus hospital management for women with PPROM before 37 weeks' gestation.

Data Collection And Analysis: Two review authors independently assessed clinical trials for eligibility for inclusion, risk of bias, and carried out data extraction.

Main Results: We included two trials (116 women) comparing planned home versus hospital management for PPROM. Overall, the number of included women in each trial was too small to allow adequate assessment of pre-specified outcomes. Investigators used strict inclusion criteria and in both studies relatively few of the women presenting with PPROM were eligible for inclusion. Women were monitored for 48 to 72 hours before randomisation. Perinatal mortality was reported in one trial and there was insufficient evidence to determine whether it differed between the two groups (risk ratio (RR) 1.93, 95% confidence interval (CI) 0.19 to 20.05).  There was no evidence of differences between groups for serious neonatal morbidity, chorioamnionitis, gestational age at delivery, birthweight and admission to neonatal intensive care.There was no information on serious maternal morbidity or mortality. There was some evidence that women managed in hospital were more likely to be delivered by caesarean section (RR (random-effects) 0.28, 95% CI 0.07 to 1.15). However, results should be interpreted cautiously as there is moderate heterogeneity for this outcome (I² = 35%). Mothers randomised to care at home spent approximately 10 fewer days as inpatients (mean difference -9.60, 95% CI -14.59 to -4.61) and were more satisfied with their care. Furthermore, home care was associated with reduced costs.

Authors' Conclusions: The review included two relatively small studies that did not have sufficient statistical power to detect meaningful differences between groups. Future large and adequately powered randomised controlled trials are required to measure differences between groups for relevant pre-specified outcomes. Special attention should be given to the assessment of maternal satisfaction with care and cost analysis as they will have social and economic implications in both developed and developing countries.
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http://dx.doi.org/10.1002/14651858.CD008053.pub3DOI Listing
April 2014

Treatment for primary postpartum haemorrhage.

Cochrane Database Syst Rev 2014 Feb 13(2):CD003249. Epub 2014 Feb 13.

University Department of Obstetrics and Gynaecology, Fetal and Maternal Medicine Unit, Leicester Royal Infirmary, Infirmary Square, Leicester, UK, LE1 5WW.

Background: Primary postpartum haemorrhage (PPH) is one of the top five causes of maternal mortality in both developed and developing countries.

Objectives: To assess the effectiveness and safety of any intervention used for the treatment of primary PPH.

Search Methods: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 August 2013).

Selection Criteria: Randomised controlled trials comparing any interventions for the treatment of primary PPH.

Data Collection And Analysis: We assessed studies for eligibility and quality and extracted data independently. We contacted authors of the included studies to request more information.

Main Results: Ten randomised clinical trials (RCTs) with a total of 4052 participants fulfilled our inclusion criteria and were included in this review.Four RCTs (1881 participants) compared misoprostol with placebo given in addition to conventional uterotonics. Adjunctive use of misoprostol (in the dose of 600 to 1000 mcg) with simultaneous administration of additional uterotonics did not provide additional benefit for our primary outcomes including maternal mortality (risk ratio (RR) 6.16, 95% confidence interval (CI) 0.75 to 50.85), serious maternal morbidity (RR 0.34, 95% CI 0.01 to 8.31), admission to intensive care (RR 0.79, 95% CI 0.30 to 2.11) or hysterectomy (RR 0.93, 95% CI 0.16 to 5.41).  Two RCTs (1787 participants) compared 800 mcg sublingual misoprostol versus oxytocin infusion as primary PPH treatment; one trial included women who had received prophylactic uterotonics, and the other did not. Primary outcomes did not differ between the two groups, although women given sublingual misoprostol were more likely to have additional blood loss of at least 1000 mL (RR 2.65, 95% CI 1.04 to 6.75). Misoprostol was associated with a significant increase in vomiting and shivering.Two trials attempted to test the effectiveness of estrogen and tranexamic acid, respectively, but were too small for any meaningful comparisons of pre-specified outcomes.One study compared lower segment compression but was too small to assess impact on primary outcomes.We did not identify any trials evaluating surgical techniques or radiological interventions for women with primary PPH unresponsive to uterotonics and/or haemostatics.

Authors' Conclusions: Clinical trials included in the current review were not adequately powered to assess impact on the primary outcome measures. Compared with misoprostol, oxytocin infusion is more effective and causes fewer side effects when used as first-line therapy for the treatment of primary PPH. When used after prophylactic uterotonics, misoprostol and oxytocin infusion worked similarly. The review suggests that among women who received oxytocin for the treatment of primary PPH, adjunctive use of misoprostol confers no added benefit.The role of tranexamic acid and compression methods requires further evaluation. Furthermore, future studies should focus on the best way to treat women who fail to respond to uterotonic therapy.
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http://dx.doi.org/10.1002/14651858.CD003249.pub3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6483801PMC
February 2014

Would gestational age and presence of brain anomalies affect interobserver reliability of fetal head biometry? Using off-line analysis of 3-D dataset.

Ultrasound Med Biol 2012 Jan 21;38(1):69-74. Epub 2011 Nov 21.

Fetal and Maternal Medicine Department, Nottingham University Hospitals NHS Trust, Nottingham, UK.

The objective was to assess interobserver reliability of fetal head biometry using archived three-dimensional (3-D) volumes and the impact of gestational age and presence of brain anomalies on examiners' performance. Seventy nine 3-D volume datasets of fetal head were examined: 27 were normal and 52 had brain abnormalities. Off-line analysis was done by three fetal medicine experts (E1, E2 and E2), all were blinded to history and patient details. Measurements of the biparietal diameter (BPD), head circumference (HC), lateral ventricle (Vp) and transcerebellar diameter (TCD) were compared between examiners and to two-dimensional (2-D) measurements. Comparisons were made at two gestational age groups (≤22 and >22 weeks) and in presence and absence of brain anomalies. The intraclass coefficient showed a significantly high level of measurement agreement between 3-D examiners and 2-D, with values >0.9 throughout (p < 0.001). Bias was evident between 3-D examiners. E2 produced smaller measurements. The mean percentage difference between this examiner and the other two in BPD, HC, Vp and TCD measurements was significant, of 1.6%, 1%, 4.9% and 1.8%, respectively. E1 measured statistically larger for HC and TCD. E3 measured significantly larger for only BPD. The presence of anomalies was of no influence on the 3-D examiners' performance except for E3 who showed bias in BPD measurements only in cases with brain anomalies. Unlike other examiners, bias of E2 was only seen at gestational age group ≤22 weeks. Limits of agreement in measurements between observers were narrow for all parameters but were widest for the Vp measurements, being ±23% of the mean difference. Despite the above bias, the actual mean difference between examiners was small and unlikely to be of any clinical significance. Off-line measurement of fetal head biometry using 3-D volumes is reliable. In our study, presence of brain anomalies was unlikely to influence the reproducibility of measurements. Gestational age seemed to be of an impact on examiners' bias. Among experts this bias may be of no clinical significance.
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http://dx.doi.org/10.1016/j.ultrasmedbio.2011.10.016DOI Listing
January 2012

Evaluating the intra- and interobserver reliability of three-dimensional ultrasound and power Doppler angiography (3D-PDA) for assessment of placental volume and vascularity in the second trimester of pregnancy.

Ultrasound Med Biol 2011 Mar 21;37(3):376-85. Epub 2011 Jan 21.

Nottingham University Hospitals NHS Trust, Queen's Medical Centre Campus, Nottingham, United Kingdom.

Three-dimensional (3-D) power Doppler angiography (3-D-PDA) allows visualisation of Doppler signals within the placenta and their quantification is possible by the generation of vascular indices by the 4-D View software programme. This study aimed to investigate intra- and interobserver reproducibility of 3-D-PDA analysis of stored datasets at varying gestations with the ultimate goal being to develop a tool for predicting placental dysfunction. Women with an uncomplicated, viable singleton pregnancy were scanned at 12, 16 or 20 weeks gestational age groups. 3-D-PDA datasets acquired of the whole placenta were analysed using the VOCAL software processing tool. Each volume was analysed by three observers twice in the A plane. Intra- and interobserver reliability was assessed by intraclass correlation coefficients (ICCs) and Bland Altman plots. At each gestational age group, 20 low risk women were scanned resulting in 60 datasets in total. The ICC demonstrated a high level of measurement reliability at each gestation with intraobserver values >0.90 and interobserver values of >0.6 for the vascular indices. Bland Altman plots also showed high levels of agreement. Systematic bias was seen at 20 weeks in the vascular indices obtained by different observers. This study demonstrates that 3-D-PDA data can be measured reliably by different observers from stored datasets up to 18 weeks gestation. Measurements become less reliable as gestation advances with bias between observers evident at 20 weeks.
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http://dx.doi.org/10.1016/j.ultrasmedbio.2010.11.018DOI Listing
March 2011

Planned home versus hospital care for preterm prelabour rupture of the membranes (PPROM) prior to 37 weeks' gestation.

Cochrane Database Syst Rev 2010 Apr 14(4):CD008053. Epub 2010 Apr 14.

Department of Obstetrics and Gynaecology, Queen's Medical Centre, Nottingham University Hospital, Derby Road, Nottingham, Nottinghamshire, UK, NG7 2UH.

Background: Preterm prelabour rupture of membranes (PPROM) is associated with increased risk of maternal and neonatal morbidity and mortality. Women with PPROM have been predominantly managed in hospital. It is possible that selected women could be managed at home after a period of observation. The safety, cost and women's views about home management have not been established.

Objectives: To assess the safety, cost and women's views about planned home versus hospital care for women with PPROM.

Search Strategy: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (January 2010) and the reference lists of all the identified articles.

Selection Criteria: Randomised and quasi-randomised trials comparing planned home versus hospital management for women with PPROM before 37 weeks' gestation.

Data Collection And Analysis: Two review authors independently assessed clinical trials for eligibility for inclusion, risk of bias, and carried out data extraction.

Main Results: We included two trials (116 women) comparing planned home versus hospital management for PPROM. Overall, the number of included women in each trial was too small to allow adequate assessment of pre-specified outcomes. Investigators used strict inclusion criteria and in both studies relatively few of the women presenting with PPROM were eligible for inclusion. Women were monitored for 48 to 72 hours before randomisation. Perinatal mortality was reported in one trial and there was insufficient evidence to determine whether it differed between the two groups (risk ratio (RR) 1.93, 95% confidence interval (CI) 0.19 to 20.05). There was no evidence of differences between groups for serious neonatal morbidity, chorioamnionitis, gestational age at delivery, birthweight and admission to neonatal intensive care.There was no information on serious maternal morbidity or mortality. There was some evidence that women managed in hospital were more likely to be delivered by caesarean section (RR (random-effects) 0.28, 95% CI 0.07 to 1.15). However, results should be interpreted cautiously as there is a moderate heterogeneity for this outcome (I(2) = 35%). Mothers randomised to care at home spent approximately 10 fewer days as inpatients (mean difference -9.60, 95% CI -14.59 to -4.61) and were more satisfied with their care. Furthermore, home care was associated with reduced costs.

Authors' Conclusions: The review included two relatively small studies that did not have sufficient statistical power to detect meaningful differences between groups. Future large and adequately powered randomised controlled trials are required to measure differences between groups for relevant pre-specified outcomes. Special attention should be given to the assessment of maternal satisfaction with care and cost analysis as they will have social and economic implications in both developed and developing countries.
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http://dx.doi.org/10.1002/14651858.CD008053.pub2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4170988PMC
April 2010

Risk factors and interventions associated with major primary postpartum hemorrhage unresponsive to first-line conventional therapy.

Acta Obstet Gynecol Scand 2008 ;87(6):652-61

Division of Perinatal and Reproductive Medicine, University of Liverpool, Liverpool, UK.

Background: To examine risk factors and interventions associated with major primary postpartum hemorrhage (PPH) unresponsive to first-line conventional therapy.

Methods: From computerized maternity database, we identified women with major primary PPH defined as blood loss >or=1,000 ml and/or the need for a blood transfusion within 24 h of delivery beyond 24 weeks' gestation. Cases were assigned according to the mode of delivery and response to the first-line therapy (responders and non-responders).

Results: Between 1998 and 2002, 20,610 women delivered after 24 weeks' gestation. A total of 306 women developed primary PPH (14.8/1,000 deliveries) including 103 vaginal and 203 caesarean (CS) births. Out of 103 women with PPH following vaginal birth, 22 (21%) failed to respond to first-line therapy. Following CS, 20 of 203 (10%) failed first line treatment and required examination under anesthesia (EUA) and other interventions to control bleeding. Irrespective of the mode of delivery, antepartum risk factors did not differ between responders and non-responders to first-line therapy. In the vaginal group, non-responders were treated with required bimanual compression and intra-myometrial PGF(2)alpha (49%), repair of cervical tear (14%), vaginal packing (9%), and uterine packing (5%). In the CS group, hysterectomy was the most common surgical intervention (54%) after other methods including uterine packing, B-Lynch procedure, uterine tamponade, and intra-myometrial prostaglandin were ineffective.

Conclusions: The currently known risk factors for primary PPH are not useful in the identification of patients who continue to bleed after first-line therapy. Emergency hysterectomy was the most common surgical intervention used to control major PPH unresponsive to conventional therapy following CS birth.
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http://dx.doi.org/10.1080/00016340802087660DOI Listing
July 2008

Thrombin activatable fibrinolysis inhibitor and its fibrinolytic effect in normal pregnancy.

Thromb Haemost 2004 Nov;92(5):1025-31

Department of Obstetrics and Gynaecology, University of Liverpool, UK.

We investigated changes in both thrombin activatable fibrinolysis inhibitor (TAFI) antigen levels and its functional effect on in vitro fibrinolysis in normal pregnancy. 152 pregnant women and 31 women in the immediate postpartum period were studied, with pregnancy divided into 6 windows at 4 weekly intervals. As TAFI influences and is in turn influenced by components of the protein C (PC) pathway, its measurements were correlated with levels of soluble thrombomodulin, PC, protein S (PS) and the overall phenotype of activated PC resistance (APCR). Compared with mean TAFI levels at booking gestation (6.6 +/- 1.2 microg/ml), levels peaked at 35-39 weeks gestation (9.6 +/- 2 microg/ml, p = 0.001), followed by a significant drop within 24 hours of delivery (7.2 +/- 1.1 microg/ml). In functional terms, the mean clot lysis time (CLT) (101 +/- 13 min at booking) also peaked at 35-39 weeks gestation (141 +/- 42 min, p = 0.007) and dropped after delivery (99 +/- 33 min), and was significantly correlated with gestational age (r = 0.410, p = 0.001) and could be abrogated in the presence of an inhibitor to TAFI activation. A significant negative correlation was found between TAFI levels and APCR (r = -0.478, p <0.001), APCRV (r = -0.598; p <0.001), PS (r = -0.490, P <0.001) and PC (r = -0.198, p = 0.02). In summary, there is a significant increase in TAFI levels, which translates into increased CLT during pregnancy. Furthermore, changes in TAFI contribute to the increasing APCR of pregnancy.
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http://dx.doi.org/10.1160/TH04-06-0387DOI Listing
November 2004

Major postpartum hemorrhage: survey of maternity units in the United Kingdom.

Acta Obstet Gynecol Scand 2002 Aug;81(8):727-30

University Department of Obstetrics & Gynecology, Liverpool Women's Hospital, UK.

Background: To determine current clinical practice among different maternity units in the United Kingdom for the management of major postpartum hemorrhage.

Methods: A postal questionnaire was sent to 258 maternity units in the UK. It was developed to identify the definition of major postpartum hemorrhage, and to identify the medical and surgical interventions used for postpartum hemorrhage, as considered by each unit, and the type and use of thromboprophylaxis following surgery for major hemorrhage after delivery.

Results: A total of 212 (82%) returned the questionnaire, but 13 units indicated that the questionnaire was not applicable to them, leaving 199 (82%) for analysis. There was a lack of agreement between the different units regarding the definition and interventions for major postpartum hemorrhage. The majority of the units use oxytocin, ergometrine and carboprost as a 'first-line' for the treatment of postpartum hemorrhage. Hysterectomy was the most common surgical procedure (89% of units had performed at least one hysterectomy for major hemorrhage in the last 5 years). There was a lack of agreement regarding the use and choice of thromboprophylaxis following surgery for major hemorrhage.

Conclusions: Current management of major postpartum hemorrhage varies considerably. There is an urgent need to identify protocols that will reduce the need for hysterectomy in women with major hemorrhage who are unresponsive to conventional medical therapy.
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http://dx.doi.org/10.1034/j.1600-0412.2002.810807.xDOI Listing
August 2002