Recent Submissions

  • Interventions to increase vaccination against COVID-19, influenza and pertussis during pregnancy: a systematic review and meta-analysis

    Ravindram, Pahalavi (2023-12-28)
    Background: Pregnant women and their babies face significant risks from three vaccine-preventable diseases: COVID-19, influenza and pertussis. However, despite these vaccines' proven safety and effectiveness, uptake during pregnancy remains low. Methods: We conducted a systematic review (PROSPERO CRD42023399488; January 2012-December 2022 following PRISMA guidelines) of interventions to increase COVID-19/influenza/pertussis vaccination in pregnancy. We searched nine databases, including grey literature. Two independent investigators extracted data; discrepancies were resolved by consensus. Meta-analyses were conducted using random-effects models to estimate pooled effect sizes. Heterogeneity was assessed using the I2 statistics. Results: From 2681 articles, we identified 39 relevant studies (n = 168 262 participants) across nine countries. Fifteen studies (39%) were randomized controlled trials (RCTs); the remainder were observational cohort, quality-improvement or cross-sectional studies. The quality of 18% (7/39) was strong. Pooled results of interventions to increase influenza vaccine uptake (18 effect estimates from 12 RCTs) showed the interventions were effective but had a small effect (risk ratio = 1.07, 95% CI 1.03, 1.13). However, pooled results of interventions to increase pertussis vaccine uptake (10 effect estimates from six RCTs) showed no clear benefit (risk ratio = 0.98, 95% CI 0.94, 1.03). There were no relevant RCTs for COVID-19. Interventions addressed the 'three Ps': patient-, provider- and policy-level strategies. At the patient level, clear recommendations from healthcare professionals backed by text reminders/written information were strongly associated with increased vaccine uptake, especially tailored face-to-face interventions, which addressed women's concerns, dispelled myths and highlighted benefits. Provider-level interventions included educating healthcare professionals about vaccines' safety and effectiveness and reminders to offer vaccinations routinely. Policy-level interventions included financial incentives, mandatory vaccination data fields in electronic health records and ensuring easy availability of vaccinations. Conclusions: Interventions had a small effect on increasing influenza vaccination. Training healthcare providers to promote vaccinations during pregnancy is crucial and could be enhanced by utilizing mobile health technologies.
  • Early pregnancy complications including recurrent pregnancy loss and obesity

    Potdar, Neelam; Iyasere, Cecilia (2023-06-23)
    This review on early pregnancy complications and obesity will focus on the known pregnancy complications such as miscarriage (whether spontaneous or after fertility treatment), polycystic ovaries and risk of miscarriage, recurrent pregnancy loss, ectopic pregnancy, hyperemesis gravidarum and birth defects. Evidence will be assessed and mechanistic pathways for the outcomes will be described. We know that obesity is now a pandemic and has an impact on early pregnancy complications. The evidence has been summarised to provide the reader with a comprehensive overview and advice for pregnant women with obesity in early pregnancy.
  • Duration of type 2 diabetes and incidence of cancer: an observational study in England

    Zaccardi, Francesco; Brown, Karen; Davies, Melanie (2023-08-28)
    Objective: To investigate the association between duration of type 2 diabetes and cancer incidence. Research design and methods: In the Clinical Practice Research Datalink database, we identified 130,764 individuals with type 2 diabetes aged ≥35 years at diagnosis who were linked to hospital and mortality records. We used sex-stratified Royston-Parmar models with two time scales to estimate incidence rates of all cancers, the four commonest cancers in the United Kingdom (colorectal, lung, prostate, breast), and the obesity-related cancers (e.g., liver, ovary) between 1 January 1998 and 14 January 2019, by age and diabetes duration. Results: During 1,089,923 person-years, 18,977 incident cancers occurred. At the same age, rates of all cancers in men and women did not vary across durations ranging from diagnosis to 20 years; conversely, for any duration, there was a strong, positive association between age and cancer rates. In men, the rate ratio (95% CI) comparing 20 with 5 years of duration was 1.18 (0.82-1.69) at 60 years of age and 0.90 (0.75-1.08) at 80 years; corresponding ratios in women were 1.07 (0.71-1.63) and 0.84 (0.66-1.05). This pattern was observed also for the four commonest cancers. For obesity-related cancers, although rates were generally higher in individuals with a higher BMI, there was no association with duration at any level of BMI. Conclusions: In this study, we did not find evidence of an association between duration of type 2 diabetes and risk of cancer, with the higher risk observed for longer durations related to ageing.
  • Does treatment modality affect measures of arterial stiffness in women with gestational diabetes?

    Anness, Abigail; Mousa, Hatem (2023-04-26)
    Objectives: The incidence of gestational diabetes mellitus (GDM) is increasing and is associated with adverse maternal, fetal and neonatal outcomes. Arterial stiffness (AS) is raised in pregnancies complicated by placental-mediated diseases such as pre-eclampsia. We investigated if AS is different between healthy pregnancies and women with GDM on different treatment modalities. Methods: We conducted a prospective longitudinal cohort study to assess and compare AS in pregnancies complicated by GDM with low-risk controls. AS, measured by pulse wave velocity (PWV) and brachial (BrAIx) and aortic (AoAIx) augmentation Index, was recorded using the Arteriograph® at four gestational windows: 24+0 to 27+6; 28+0 to 31+6; 32+0 to 35+6 and ≥36+0 weeks of gestation (windows W1-W4, respectively). Women with GDM were considered both as a single group, and as subgroups defined by treatment modality. Data were analyzed using a linear mixed model on each AS variable (log-transformed) with group, gestational windows, maternal age, ethnicity, parity, body mass index, mean arterial pressure and heart rate as fixed effects and individual as a random effect. We compared the group means including relevant contrasts and adjusted the p-values using the Bonferroni correction. Results: The study population comprised 155 low-risk controls and 127 with GDM, of whom 59 were treated with dietary intervention, 47 with metformin alone and 21 with metformin plus insulin. The two-way interaction term of study group and gestational age was significant for BrAIx and AoAIx (p<0.001), though there was no evidence (p=0.729) that mean AoPWV was different between the study groups. Women in the control group demonstrated significantly lower BrAIx and AoAIX at gestational windows W1-3 compared to the combined GDM group, but not at W4. Mean (95% CI) difference in log adjusted BrAIx was -0.37 (-0.52, 0.22), -0.23 (-0.35, -0.12), and -0.29 (-0.40, -0.18) at W1, W2 and W3, respectively. Mean (95% CI) difference in log adjusted AoAIx was -0.49 (-0.69, -0.3), -0.32 (-0.47, -0.18) and -0.38 (-0.52, -0.24) at W1, W2 and W3, respectively. Similarly, women in the control group also demonstrated significantly lower BrAIx and AoAIx compared with each of the GDM treatment subgroups (diet, metformin and metformin plus insulin) at W1-3. The increase in mean BrAIx and AoAIx seen between W2 and W3 in the women with GDM treated with dietary management was attenuated in the metformin and metformin with insulin groups, however the mean differences in BrAIx and AoAIx between these treatment groups were not statistically significant at any gestational window. Conclusions: Pregnancies complicated by GDM demonstrate significantly higher AS compared to low-risk pregnancies regardless of treatment modality. Our data provides a basis for further investigation into the association of metformin therapy with changes in AS and risk of placental-mediated diseases. This article is protected by copyright. All rights reserved.
  • Nelson syndrome and perinatal challenges: A case report and systematic review of the literature

    Jones, Kate; Reis, Ines; Levy, Miles; Potdar, Neelam (2023-05-02)
    Nelson syndrome is a rare and potentially life-threatening complication of treatment with total bilateral adrenalectomy for women with Cushing disease. A successful term pregnancy following fertility treatment in a patient with Nelson syndrome is presented. Our study provides guidance in the prenatal and intrapartum management of this condition. A case report and a systematic review of 14 papers describing 50 pregnancies are presented. An electronic database search included Medline (1946 to September 2022), Embase (1980 to September 2022), Cochrane Library, and UKOSS. A small number of pregnancies in women with Nelson syndrome are reported in literature, but there are no guidelines. Some authors detail the prenatal care provided to their patients. Four studies report prenatal monitoring with visual field checks and two report monitoring with X-rays. Five studies report the use of parenteral hydrocortisone at the time of delivery. Where described, women delivered appropriately grown newborns at term, with timing and mode of delivery dictated by obstetric indications. Preconception counseling and optimization of maternal health status improve pregnancy outcomes in women with Nelson syndrome. Multidisciplinary review in a combined obstetric-endocrine prenatal clinic is ideal. Awareness about potential complications during pregnancy and the postnatal period is crucial in providing optimal care to the mother and baby.
  • Direct current cardioversion in pregnancy: a multicentre study

    Bolger, Aidan; Siddiqui, Farah (2023-04-11)
    Objective: Direct current cardioversion (DCCV) in pregnancy is rarely required and typically only documented in single case reports or case series. A recent UK confidential enquiry reported on several maternal deaths where appropriate DCCV appeared to have been withheld. Design: Retrospective cohort study. Setting: Seventeen UK and Ireland specialist maternity centres. Sample: Twenty-seven pregnant women requiring DCCV in pregnancy. Main outcome measures: Maternal and fetal outcomes following DCCV. Results: Twenty-seven women had a total of 29 DCCVs in pregnancy. Of these, 19 (70%) initial presentations were to Emergency Departments and eight (30%) to maternity settings. There were no maternal deaths. Seventeen of the women (63%) had a prior history of heart disease. Median gestation at DCCV was 28 weeks, median gestation at delivery was 35 weeks, with a live birth in all cases. The abnormal heart rhythms documented at the first cardioversion were atrial fibrillation in 12/27 (44%) cases, atrial flutter in 8/27 (30%), supraventricular tachycardia in 5/27 (19%) and atrial tachycardia in 2/27 (7%). Fetal monitoring was undertaken following DCCV on 14/29 (48%) occasions (10 of 19 (53%) at ≥26 weeks) and on 2/29 (7%) occasions, urgent delivery was required post DCCV. Conclusions: Direct current cardioversion in pregnancy is rarely required but should be undertaken when clinically indicated according to standard algorithms to optimise maternal wellbeing. Once the woman is stable post DCCV, gestation-relevant fetal monitoring should be undertaken. Maternity units should develop multidisciplinary processes to ensure pregnant women receive the same standard of care as their non-pregnant counterparts.
  • Blood biomarkers to predict the onset of pre-eclampsia: A systematic review and meta-analysis

    Khunti, Kamlesh; Tan, Bee (2022-11-04)
    Pre-eclampsia is one of the most common pregnancy complications, and a major cause of fetal and maternal morbidity and mortality globally. Diagnosis currently takes place in the third trimester based on clinical symptoms. This systematic review and meta-analysis sought to determine the blood biomarkers that are associated with pre-eclampsia, and in particular, the biomarkers that could predict pre-eclampsia in early pregnancy. We searched the electronic databases (Medline, Embase, Cochrane Library) from inception up to March 2022. Prospective studies with 1000 or more participants that measured blood biomarkers to predict or diagnose pre-eclampsia have been included in this systematic review. Biomarkers' measurements were considered from the first up to the third trimester, but not during labor. Data concerning pre-eclampsia, biomarker measurements and study characteristics were extracted. Meta-analysis was performed when possible. We found a total of 43 studies (assessing 62 different biomarkers in 18,170 pregnancies, have been included in this systematic review, and a total of 6 studies (assessing 2 biomarkers have been included in the meta-analysis). Statistical analysis was performed for PlGF and sFlt-1. Mean difference in PlGF levels between pre-eclampsia and healthy pregnancies, appear to increase as the pregnancy progresses. Results of sFlt-1 meta-analysis were inconclusive. No significant publication bias was identified. This is the most comprehensive and up to date systematic review and meta-analysis on this important topic on blood biomarkers for the early prediction of pre-eclampsia. Further This research highlights the urgent needed for further discovery research to identify blood biomarkers that could predict the development of pre-eclampsia.
  • Spontaneous coronary artery dissection associated with infertility treatment

    Iyasere, Cecilia (2022-09-26)
    Assisted conception involving hormonals is a risk factor for spontaneous coronary artery dissection (SCAD), and pregnant women with spontaneous coronary artery dissection are more likely to have had treatment for subfertility. Increasingly, there is a risk of maternal death in women after assisted conception, and so, the need to assess the cardiovascular sequelae after assisted conception is imperative. This is an illustrative case of spontaneous coronary artery dissection shortly after a repeat cycle of in vitro fertilisation (IVF). The aetiology of spontaneous coronary artery dissection is believed to be multi-factorial, affecting mostly young women, a population similar to women requiring assisted conception. The oestrogen and progesterone used in in vitro fertilisation are believed to trigger structural weakening in the coronary blood vessels, leading to vascular rupture. Repeat in vitro fertilisation cycles and successful conception are thought to increase spontaneous coronary artery dissection risk by increasing hormonal exposure. The management of spontaneous coronary artery dissection is dependent on if pregnancy has been achieved or not, and a multi-disciplinary approach to its management is essential. More research is needed to identify women at higher risk of this life-threatening event.
  • Control measurements of escherichia coli Biofilm: A review

    Tan, Bee (2022-08-16)
    Escherichia coli (E. coli) is a common pathogen that causes diarrhea in humans and animals. In particular, E. coli can easily form biofilm on the surface of living or non-living carriers, which can lead to the cross-contamination of food. This review mainly summarizes the formation process of E. coli biofilm, the prevalence of biofilm in the food industry, and inhibition methods of E. coli biofilm, including chemical and physical methods, and inhibition by bioactive extracts from plants and animals. This review aims to provide a basis for the prevention and control of E. coli biofilm in the food industry.
  • Haemolysis, elevated liver enzymes and low platelets: Diagnosis and management in critical care

    Poimenidi, Evangelia; Archer, Natasha (2021-06-17)
    A thirty-year-old pregnant woman was admitted to hospital with headache and gastrointestinal discomfort. She developed peripheral oedema and had an emergency caesarean section following an episode of tonic-clonic seizures. Her delivery was further complicated by postpartum haemorrhage and she was admitted to the Intensive Care Unit (ICU) for further resuscitation and seizure control which required infusions of magnesium and multiple anticonvulsants. Despite haemodynamic optimisation she developed an acute kidney injury with evidence of liver damage, thrombocytopenia and haemolysis. Haemolysis, Elevated Liver enzymes and Low Platelets (HELLP) syndrome, a multisystem disease of advanced pregnancy which overlaps with pre-eclampsia, was diagnosed. HELLP syndrome is associated with a range of complications which may require critical care support, including placental abruption and foetal loss, acute kidney injury, microangiopathic haemolytic anaemia, acute liver failure and liver capsule rupture. Definitive treatment of HELLP is delivery of the fetus and in its most severe forms requires admission to the ICU for multiorgan support. Therapeutic strategies in ICU are mainly supportive and include blood pressure control, meticulous fluid balance and possibly escalation to renal replacement therapy, mechanical ventilation, neuroprotection, seizure control, and management of liver failure-related complications. Multidisciplinary input is essential for optimal treatment.
  • Building leadership capabilities in maternity

    Ashmore, Ayisha; Archer, Natasha (2021-11-26)
    Background: Over recent years, there has been increasing recognition that effective leadership is critical to establishing positive organisational culture and improving patient outcomes. In maternity, there is a unique interplay between different specialties and disciplines in providing high-quality services. Methods: Review of literature pertaining to leadership and maternity. Results: Good leadership is the key determinant in ensuring that our multi-professional teams function effectively. The relational aspects of teamworking, linked to safer delivery of services, have been explored in great detail in maternity services. However, there has been less focus on the application of leadership theory in this environment and the impact of interventions used in developing leadership skills within maternity teams. Conclusions: In this paper, we discuss how leadership theory can be used to understand high profile maternity service failures and how effective team culture, clinical team building and individual leadership skill-development are strong contributors to this thinking. Specific examples are used to describe ongoing work in our drive for improvement and to highlight the current lack of evidence in this area.
  • Screening for type 2 diabetes after a diagnosis of gestational diabetes by ethnicity: A retrospective cohort study

    Khunti, Kamlesh; Davies, Melanie (2022-03-26)
    Aims: To estimate rates and identify determinants of post-partum glucose screening attendance in women with a history of gestational diabetes mellitus (GDM). Methods: Retrospective cohort study using the Clinical Practice Research Datalink linked to Hospital Episode Statistics, to identify women diagnosed with GDM between 01/01/2000 and 05/11/2018. Age adjusted odds ratios (aOR) and 95% confidence intervals (CI) were estimated using multivariable logistic regression models. Results: In 10,868 women with GDM, with an average follow-up of 5.38 years (95% CI 5.31,5.45), there was an average of 3.79 (95% CI 3.70,3.89) screening episodes per individual, with a mean time to first screening test of 1.22 (95% CI 1.18, 1.25) years. South Asian women had a significantly greater likelihood of being screened compared to White women within the first 5 years post-partum, aOR: 1.89 95% CI (1.20,2.98). A low proportion of women received at least one test per year of follow-up (23.87%). Older age at GDM diagnosis, polycystic ovary syndrome, prescribed medication for GDM, and living in England, were all associated with a greater likelihood of being screened. Conclusion: While the majority of women with previous GDM receive at least one glucose screening test within the first 5 years post-partum, fewer than a quarter of them receive on average one test per year of follow-up. Developing strategies to motivate more women to attend screening in primary care is essential.
  • Effects of supervised exercise on the development of hypertensive disorders of pregnancy: A systematic review and meta-analysis

    Khunti, Kamlesh; Tan, Bee (2022-02-01)
    Hypertensive disorders of pregnancy (HDP) are the most common medical complication in pregnancy, affecting approximately 10-15% of pregnancies worldwide. HDP are a major cause of maternal and perinatal morbidity and mortality, and each year, worldwide, around 70,000 mothers and 500,000 babies die because of HDP. Up-to-date high-quality systematic reviews quantifying the role of exercise and the risks of developing HDP are currently lacking. Physical exercise is considered to be safe and beneficial to pregnant women. Supervised exercise has been shown to be safe and to be more beneficial than unsupervised exercise in the general population, as well as during pregnancy in women with obesity and diabetes. Therefore, we undertook a systematic review and meta-analysis to investigate the effects of women performing supervised exercise during pregnancy compared to a control group (standard antenatal care or unsupervised exercise) on the development of HDP. We searched Medline, Embase, CINHAL, and the Cochrane Library, which were searched from inception to December 2021. We included only randomized controlled trials (RCTs) investigating the development of HDP compared to a control group (standard antenatal care or unsupervised exercise) in pregnant women performing supervised exercise. Two independent reviewers selected eligible trials for meta-analysis. Data collection and analyses were performed by two independent reviewers. The PROSPERO registration number is CRD42020176814. Of 6332 articles retrieved, 16 RCTs met the eligibility criteria, comparing a total of 5939 pregnant women (2904 pregnant women in the intervention group and 3035 controls). The risk for pregnant women to develop HDP was significantly reduced in the intervention compared to the control groups, with an estimated pooled cumulative incidence of developing HDP of 3% in the intervention groups (95% CI: 3 to 4) and of 5% in the control groups (95% CI: 5 to 6), and a pooled odds ratio (OR) comparing intervention to control of 0.54 (95% CI:0.40 to 0.72, p < 0.001). A combination of aerobic and anaerobic exercise, or yoga alone, had a greater beneficial effect compared to performing aerobic exercise only (mixed-OR = 0.50, 95% CI:0.33 to 0.75, p = 0.001; yoga-OR = 0.28, 95% CI:0.13 to 0.58, p = 0.001); aerobic exercise only-OR = 0.87, 95% CI:0.55 to 1.37, p = 0.539). Pregnancy is an opportunity for healthcare providers to promote positive health activities, thus optimizing the health of pregnant women with potential short- and long-term benefits for both mother and child. This systematic review and meta-analysis support a beneficial effect of either structured exercise (combination of aerobic, strength, and flexibility workouts) or yoga for preventing the onset of HDP. Yoga, considered a low-impact physical activity, could be more acceptable and safer for women in pregnancy in reducing the risk of developing HDP.
  • Pregnancies in women with Turner syndrome: a retrospective multicentre UK study

    Bolger, Aidan; Siddiqui, Farah (2021-11-20)
    Objective: To determine the characteristics and outcomes of pregnancy in women with Turner syndrome. Design: Retrospective 20-year cohort study (2000-20). Setting: Sixteen tertiary referral maternity units in the UK. Population or sample: A total of 81 women with Turner syndrome who became pregnant. Methods: Retrospective chart analysis. Main outcome measures: Mode of conception, pregnancy outcomes. Results: We obtained data on 127 pregnancies in 81 women with a Turner phenotype. All non-spontaneous pregnancies (54/127; 42.5%) were by egg donation. Only 9/31 (29%) pregnancies in women with karyotype 45,X were spontaneous, compared with 53/66 (80.3%) pregnancies in women with mosaic karyotype 45,X/46,XX (P < 0.0001). Women with mosaic karyotype 45,X/46,XX were younger at first pregnancy by 5.5-8.5 years compared with other Turner syndrome karyotype groups (P < 0.001), and more likely to have a spontaneous menarche (75.8% versus 50% or less, P = 0.008). There were 17 miscarriages, three terminations of pregnancy, two stillbirths and 105 live births. Two women had aortic dissection (2.5%); both were 45,X karyotype with bicuspid aortic valves and ovum donation pregnancies, one died. Another woman had an aortic root replacement within 6 months of delivery. Ten of 106 (9.4%) births with gestational age data were preterm and 22/96 (22.9%) singleton infants with birthweight/gestational age data weighed less than the tenth centile. The caesarean section rate was 72/107 (67.3%). In only 73/127 (57.4%) pregnancies was there documentation of cardiovascular imaging within the 24 months before conceiving. Conclusions: Pregnancy in women with Turner syndrome is associated with major maternal cardiovascular risks; these women deserve thorough cardiovascular assessment and counselling before assisted or spontaneous pregnancy managed by a specialist team. Tweetable abstract: Pregnancy in women with Turner syndrome is associated with an increased risk of aortic dissection.
  • Clinical aspects of oocyte retrieval and embryo transfer: tips and tricks for the novice and the expert

    Gelbaya, Tarek (2022-02-18)
    Oocyte retrieval (ovum pick-up) and embryo transfer (ET) are essential steps in in-vitro fertilization and intracytoplasmic sperm injection and over the years, the two procedures were developed in order to improve the clinical outcome. Many suggestions were proposed and applied before, during and after oocyte retrieval such as timing of HCG trigger, pre-operative pelvic scan, vaginal cleansing, type of anesthesia, type and gauge of aspiration needles, aspiration pressure, follicle flushing, and the need for prophylactic antibiotics. Similarly, many steps were suggested and implemented before, during and after ET including patient's position, type of anesthesia/analgesia, dummy (mock) ET, ultrasound-guidance, HCG injection in the uterine cavity, use of relaxing agents, full bladder, removal of the cervical mucus, flushing the cervix with culture medium, type of ET catheter, embryo loading techniques, site of embryo deposition, the use of adherence compounds, as well as bed rest after ET. Complications were also reported with oocyte retrieval and ET. The aim of this review is to evaluate the current practice of these two procedures in the light of available evidence.
  • Pregnancy outcomes after transcervical radiofrequency ablation of uterine fibroids with the sonata system

    Habiba, Marwan
    Objective: To describe pregnancy outcomes in women who conceived after undergoing transcervical fibroid ablation (TFA) as treatment for symptomatic uterine fibroids. Materials and methods: TFA was used to treat symptomatic uterine fibroids with radiofrequency energy, both under clinical trial protocol and commercial usage in hospitals in Europe, the United Kingdom, Mexico, and the United States. All women who reported pregnancies to their physicians after undergoing TFA with the Sonata® System and provided consent for use of their data were included. Results: There have been 36 pregnancies representing 20 deliveries among 28 women who were treated with TFA. Five women conceived more than once postablation, and four conceived as a result of assisted reproductive technology (ART). Outcomes include 8 vaginal deliveries, 12 Cesarean sections, 3 therapeutic abortions, and 8 first trimester spontaneous abortions (four occurring in a patient with a history of recurrent pregnancy loss and an immunologic disorder). Five women are currently pregnant, two of whom previously delivered after TFA. There were no 5-minute Apgar scores <7, and all neonates weighed >2500 g. All deliveries occurred at ≥37 weeks except for one delivery at 35 6/7 weeks. There were no uterine ruptures or abnormal placentation and no reports of postpartum hemorrhage or stillbirths. Ablated fibroids included transmural, submucous, and intramural myomata up to 7 cm in diameter. Conclusions: Normal pregnancy outcomes at term have occurred after TFA with the Sonata System, including in women with recurrent abortion and in those undergoing ART. There were no instances of low Apgar scores, low birthweight, stillbirth, postpartum hemorrhage, or uterine rupture (FAST-EU, NCT01226290; SONATA, NCT02228174; SAGE, NCT03 118037). (J GYNECOL SURG 38:207).
  • A case series review of patients with Thrombocytopenia and Absent-Radii syndrome (TARS) and their management during pregnancy

    Halperin, Daniel; Myers, Bethan (2021)
    Bleeding diatheses due to platelet-related disorders can present challenges to treating clinicians, especially in the context of peri- and post-partum patients in the obstetric setting. Thrombocytopenia and Absent-Radii syndrome (TARS) is an inherited disorder characterized by reduced bone marrow platelet production, skeletal deformities affecting radii and other limbs; cardiac, renal, and other heterogeneous anomalies may occur. It is caused by the co-inheritance of a microdeletion and a nucleotide polymorphism in the RBM8A gene on chromosome 1. Bleeding phenotype is more severe than platelet numbers which might predict especially in infants but improves with age. There is minimal literature regarding the impact of pregnancy and puerperium. We describe the management of three pregnancies in the hematology-obstetrics clinic. As platelet counts normally decrease through pregnancy, close monitoring is required in TARS. No major bleeding was seen antenatally but two required platelet transfusions during labor. No other treatment definitely improves bleeding, although case reports of steroids claim variable success. Tranexamic acid may be helpful, and thrombopoietin agonists represent a potential future option.
  • Maternal hemodynamics and neonatal birth weight in pregnancies complicated by gestational diabetes: new insights from novel causal inference analysis modeling

    Anness, Abigail; Webb, David; Mousa, Hatem
    Objectives: Normal pregnancy is characterised by significant changes in maternal hemodynamics which correlate with fetal growth. Pregnancies complicated by gestational diabetes (GDM) are associated with large for gestational age (LGA) and macrosomia, but the relationship between maternal hemodynamic parameters and birthweight among women with GDM is yet to be established. Our objective was to investigate the influence of maternal hemodynamics on neonatal birthweight in healthy pregnancies and those complicated by GDM. Methods: We conducted a prospective cross-sectional case controlled study. GDM was defined as a fasting glucose ≥5.3mmol/L, and/or serum glucose of ≥7.8mmol/L 2 hours following a 75g oral glucose load. Data were collected on maternal characteristics and pregnancy outcomes, including body mass index (BMI) and birth weight centile, adjusted for gestation at delivery. Maternal hemodynamics were assessed using the Arteriograph® and bioreactance techniques at 34-42 weeks gestation. Graphical causal inference methodology was used to identify causational effects of the measured variables on neonatal birthweight centile. Results: 141 women with GDM and 136 normotensive non-diabetic controls were included in the analysis. 62% of the women with GDM were managed pharmacologically, with metformin and/or insulin. Variables included in the final model were cardiac output (CO), mean arterial pressure (MAP), total peripheral resistance (TPR), aortic augmentation index (AIx), pulse wave velocity (PWV) and BMI. Among controls, maternal BMI, CO and aortic PWV were significantly associated with neonatal birthweight. Each standard deviation increase in BMI, CO and PWV produced an increase of 8.4 (p=0.002), 9.4 (p=0.008) and 7.1 (p=0.017) birth weight centiles, respectively. We found no significant relationship between MAP, TPR or aortic AIx and neonatal birthweight. Among the women with GDM, maternal hemodynamics influenced neonatal birth weight in a similar manner to the control group. Only the relationship between maternal BMI and neonatal birthweight reached statistical significance, with a 1 standard deviation increase in BMI producing a 6.1 centile increase in the birthweight (p=0.019). Conclusions: Maternal BMI, CO and PWV were determinants of birthweight in our control group. The relationship between maternal hemodynamics and neonatal birthweight is similar between women with GDM and healthy controls. Our findings demonstrate that FGR in pregnancies complicated by GDM may indicate maternal cardiovascular dysfunction. The differences between our findings and that of previous work could be reconciled by a non-linear relationship between MAP and neonatal birthweight, which warrants further investigation. This article is protected by copyright. All rights reserved.
  • The impact of chronic kidney disease Stages 3-5 on pregnancy outcomes

    Brunskill, Nigel; Carr, Sue (2021-11)
    Background: Contemporaneous data are required for women with chronic kidney disease (CKD) Stages 3-5 to inform pre-pregnancy counselling and institute appropriate antenatal surveillance. Methods: A retrospective cohort study in women with CKD Stages 3-5 after 20 weeks' gestation was undertaken in six UK tertiary renal centres in the UK between 2003 and 2017. Factors predicting adverse outcomes and the impact of pregnancy in accelerating the need for renal replacement therapy (RRT) were assessed. Results: There were 178 pregnancies in 159 women, including 43 women with renal transplants. The live birth rate was 98%, but 56% of babies were born preterm (before 37 weeks' gestation). Chronic hypertension was the strongest predictor of delivery before 34 weeks' gestation. Of 121 women with known pre-pregnancy hypertension status, the incidence of delivery before 34 weeks was 32% (31/96) in women with confirmed chronic hypertension compared with 0% (0/25) in normotensive women. The risk of delivery before 34 weeks doubled in women with chronic hypertension from 20% [95% confidence interval (CI) 9-36%] to 40% (95% CI 26-56%) if the gestational fall in serum creatinine was <10% of pre-pregnancy concentrations. Women with a urinary protein:creatinine ratio >100 mg/mmol prior to pregnancy or before 20 weeks' gestation had an increased risk for birthweight below the 10th centile (odds ratio 2.57, 95% CI 1.20-5.53). There was a measurable drop in estimated glomerular filtration rate (eGFR) between pre-pregnancy and post-partum values (4.5 mL/min/1.73 m2), which was greater than the annual decline in eGFR prior to pregnancy (1.8 mL/min/1.73 m2/year). The effect of pregnancy was, therefore, equivalent to 1.7, 2.1 and 4.9 years of pre-pregnancy renal disease in CKD Stages 3a, 3b and 4-5, respectively. The pregnancy-associated decline in renal function was greater in women with chronic hypertension and in those with a gestational fall in serum creatinine of <10% of pre-pregnancy concentrations. At 1 year post-partum, 46% (58/126) of women had lost ≥25% of their pre-pregnancy eGFR or required RRT. Most women with renal transplants had CKD Stage 3 and more stable renal function prior to pregnancy. Renal transplantation was not independently associated with adverse obstetric or renal outcomes. Conclusions: Contemporary pregnancies in women with CKD Stages 3-5 are complicated by preterm delivery, low birthweight and loss of maternal renal function. Chronic hypertension, pre- or early pregnancy proteinuria and a gestational fall in serum creatinine of <10% of pre-pregnancy values are more important predictors of adverse obstetric and renal outcome than CKD Stages 3-5. Pregnancy in women with CKD Stages 3-5 advances the need for dialysis or transplantation by 2.5 years.