Trends in family planning and counselling for women with sickle cell disease in the UK over two decades.

BACKGROUND: Pregnancies in women with sickle cell disease (SCD) are known to have high rates of maternal and fetal mortality and morbidity. Given these pregnancy-associated problems for women with SCD, advice both about pregnancy planning and about effective contraception are of paramount importance. This study sought to discover the contraception methods used by women with SCD, what complications women with SCD encounter with contraception, and their experiences of pre-pregnancy counselling and pregnancy planning, and how such issues may have changed over the past two decades. METHOD: The study was a multicentre, interview-based, cross-sectional study. Interviews were carried out with 102 women with SCD, in north and central London during 2010, concerning their current and previous contraceptive use, their pregnancy history, their menstrual history, and the advice they received concerning pregnancy planning and contraception. Patient information was anonymised and ethical approval was obtained. These data were compared with data from a similar study undertaken in 1993. RESULTS: There were significant differences in a number of key areas: the number of unplanned pregnancies decreased from 64% in 1993 to 53% in 2010. The number of women with SCD who were advised not to become pregnant also fell, from 36% to 15%. The use of combined oral contraceptive pills declined, from 45% of the women in 1993 to 31% in 2010. Conversely the use of depot medroxyprogesterone acetate contraception (DMPA) and the levonorgestrel intrauterine system (LNG-IUS) both increased. CONCLUSIONS: Significant changes in the contraceptive methods used by women with SCD are demonstrated in the London population. LNG-IUS use in SCD has not been investigated before. There has been an encouraging decrease in the number of women with SCD who are advised not to become pregnant, perhaps reflecting an improvement in their overall health. Although the number of unplanned pregnancies has fallen, it remains high - emphasising the continuing need for women with SCD to have access to informed advice about pregnancy-associated issues and contraception.

Raised concentrations of lipid peroxidation products (LPO) in pregnant women with impaired glucose tolerance.

INTRODUCTION: Lipid peroxidation (LPO) results from oxidative damage to membrane lipids. Whereas LPO rises in normal pregnancy, the effect of gestational diabetes mellitus (GDM) on this process has not been clearly defined. MATERIALS AND METHOD: Fasting blood concentrations of malondialdehyde+4-hydroxyalkenals (MDA+4-HDA), as LPO index, TNFa soluble receptors (sTNF-R1 and sTNF-R2), and soluble adhesion molecules (sICAM-1, sVCAM-1), were measured in 51 women at 28 weeks of gestation. The women were divided according to the results of 50.0 g glucose challenge test (GCT) and 75.0 g oral glucose tolerance test (OGTT): Controls (n=20), normal responses to both GCT and OGTT; Intermediate Group (IG) (n=15), abnormal GCT but normal OGTT; GDM group (n=16), abnormal both GCT and OGTT. RESULTS: Glucose concentrations in women diagnosed with GDM were within the range of impaired glucose tolerance. There were no significant differences in concentrations of either TNF a soluble receptors R1 and R2, or sICAM-1 or sVCAM-1. LPO concentrations [MDA+4-HDA (nmol/mg protein)] were significantly higher in women with GDM than in the other two groups [64.1±24.3 (mean±SD), 39.3±23.1, 47.0±18.1, for GDM, IG and Controls, respectively; p<0.05]. In multivariate analysis, the only significant independent correlation was between LPO level and glucose at 120 minutes of OGTT (rs=0.42; p=0.009). CONCLUSIONS: Oxidative damage to membrane lipids is increased in GDM and might result directly from hyperglycaemia. Physiological significance of this phenomenon remains to be elucidated.

Serum levels of matrix metalloproteinases MMP-2 and MMP-9 and their inhibitors in women with glucose intolerance in pregnancy and normal controls.

AIM: Matrix metalloprotenases (MMPs) are proteolytic enzymes active in inflammatory states. We have examined MMP-9, MMP-2, and their respective tissue inhibitors: TIMP-1 and TIMP-2 in sera of women with gestational diabetes mellitus (GDM) and various degrees of insulin resistance (IR) in the third trimester of pregnancy. METHODS: Fasting serum levels of MMP-9, MMP-2, TIMP-1 and TIMP-2 were measured in 26th-28th week of gestation in 51 women divided according to their response to a 50-g glucose challenge test (GCT) and a 75-g OGTT: controls (n = 20): both tests normal; the GDM group (n = 16) both tests abnormal; the intermediate group (IG; n = 15) abnormal GCT and normal OGTT. MMPs and TIMPs were correlated with the parameters of IR: homeostasis model assessment (HOMA) and insulin resistance index (IRI). RESULTS: MMP-9, MMP-2, TIMP-1 and MMP-9/TIMP-1 ratio were not different among the groups. TIMP-2 levels were significantly higher in the GDM and IG groups than in controls (p < 0.01). MMP-2/TIMP-2 ratio was lower in the GDM group than in the other groups (p < 0.01) and was correlated to HOMA and IRI (r = -0.465 and r = -0.43 respectively, p < 0.01). CONCLUSIONS: Serum MMP levels do not reflect inflammation in GDM. Elevated TIMP-2 and consequently lower MMP-2/TIMP-2 levels in GDM need to be clarified, but are unlikely to be a consequence of inflammation.

Elevated concentrations of retinol-binding protein-4 (RBP-4) in gestational diabetes mellitus: negative correlation with soluble vascular cell adhesion molecule-1 (sVCAM-1).

BACKGROUND: Retinol-binding protein-4 (RBP-4) may increase insulin resistance (IR) in animals, with elevated levels reported in humans with obesity and type 2 diabetes. There are, however, few data on concentrations of RBP-4 in gestational diabetes mellitus (GDM). METHODS: We measured fasting serum levels of RBP-4, soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) in 50 women at 28 weeks of gestation, divided according to the results of a 50 g glucose challenge test (GCT) and a 75 g oral glucose tolerance test (OGTT): (1) controls (n = 20), normal responses to both GCT and OGTT; (2) intermediate group (IG) (n = 15): false positive GCT, but normal OGTT; and (3) GDM group (n = 15), both GCT and OGTT abnormal. IR was assessed by homeostasis model assessment (HOMA-IR) and by insulin resistance index (IRI) based on glycemia and insulinemia during OGTT. RESULTS: All groups were matched for age and body mass index (BMI). RBP-4 levels (microg/ml, mean+/-standard deviation) were higher in women with GDM vs. controls (53.9 +/- 17.9 vs. 29.7 +/- 13.9, p < or = 0.001), with a trend towards higher RBP-4 in GDM compared with IG (38.0 +/- 19.3, p = 0.07). There was no significant correlation between RBP-4 and age, BMI, insulin, IRI or HOMA-IR, but there was a moderate, significant negative correlation between RBP-4 and sVCAM-1 (r(2) = 0.20, p = 0.001). CONCLUSIONS: RBP-4 levels are elevated in women with GDM, but do not correlate with IR indices and correlate negatively with sVCAM-1. The physiological significance of RBP-4 rise in women with GDM remains to be elucidated.

Fertility and pregnancy in thalassemia major.

Over the last 15 years, 22 women with thalassemia major have completed 29 pregnancies at the Royal Hospital in London. The major pre-pregnancy issues, medications, and pregnancy care are reviewed. Experience suggests that, with proper care and guidance, pregnancies among women with thalassemia major are practical and can have successful outcomes.

Binding of ovarian steroids to erythrocytes in patients with sickle cell disease; effects on cell sickling and osmotic fragility.

Ovarian steroids appear to influence the manifestations of sickle cell disease (SCD); oestrogens can adversely affect erythrocyte function, whereas progestogens may inhibit sickling and decrease the osmotic fragility of erythrocytes. The aims of the present studies were: (i) to characterise the binding of oestradiol and progesterone to erythrocytes from women with HbSS, HbSC and HbAA genotypes; (ii) to investigate whether steroids modulate susceptibility to sickling or osmotic fragility of HbSS and HbAA erythrocytes. Erythrocytes were incubated for 1h with [3H]-steroids at 4 and 37 degrees C. Binding of both oestradiol and progesterone was independent of temperature and steroid concentration, but was decreased by sequential "washing" of erythrocytes in fresh incubation buffer. Binding capacity was 80 +/- 6% greater for oestradiol (versus progesterone) in all three genotypes, and binding of both steroids was decreased by > or = 70% in HbSS erythrocytes compared to HbSC or HbAA erythrocytes. Pre-incubation of erythrocytes with 35 microM oestradiol or 30 microM progesterone had no significant effect on susceptibility of HbSS and HbAA erythrocytes to sickling, or on osmotic fragility. We conclude that both oestradiol and progesterone bind in a low affinity, non-saturable manner to erythrocytes with decreased binding in cells from women with HbSS. However, steroid binding does not affect susceptibility to sickling or osmotic fragility irrespective of haemoglobin genotype.