Recent Submissions

  • 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.