Pregnancy-associated venous thrombosis.

Pregnant women are at an increased risk of venous thromboembolism (VTE) and the consequences of an acute event in pregnancy can be debilitating, long-lasting or fatal. Screening for risk factors early in pregnancy and the provision of thromboprophylaxis are useful ways of preventing VTE in some women, but even when performed diligently, acute events are likely to remain common for the foreseeable future. It is therefore important for obstetric and non-obstetric clinicians to recognize the symptoms and signs of deep vein thrombosis and pulmonary embolism in pregnancy, to understand how a diagnosis can be reached in an effective yet safe manner and to be aware of the available treatment modalities.

The use of a scoring system to guide thromboprophylaxis in a high-risk pregnant population.

Guidelines for thromboprophylaxis in pregnancy are usually based upon clinical observations and expert opinion. For optimal impact, their use must be attended by consistency in the advice given to women. In this observational study, we evaluated the performance of a scoring system, used as a guide for clinicians administering dalteparin to pregnant women at increased risk of venous thromboembolism. The work included 47 women treated with dalteparin prior to adoption of the scoring system and 58 women treated with dalteparin after its adoption. The indication for thromboprophylaxis was recorded in each case together with details of the regimen employed, obstetric, and haematological outcomes. The main outcome measure was to determine whether consistency improved after adoption of the scoring system. We also recorded the occurrence of any new venous thromboembolism, haemorrhage, the use of regional anaesthesia during labour, evidence of allergy, and thrombocytopenia. We found that use of the scoring system improved the consistency of advice and increased the mean duration of thromboprophylaxis. None of the subjects suffered venous thromboembolism after assessment using the scoring system. There was no increase in obstetric or anaesthetic morbidity when dalteparin was given antenatally period and no evidence of heparin-induced thrombocytopenia.

Induction of labour in nulliparous and multiparous women: a UK, multicentre, open-label study of intravaginal misoprostol in comparison with dinoprostone.

OBJECTIVE: To compare the efficacy and safety of a 25-microgram vaginal tablet of misoprostol (APL202) with dinoprostone (3-mg vaginal tablet) in cervical ripening and labour induction. DESIGN: A randomised, open-label, noninferiority, comparative study in two maternal populations. SETTING: Eighteen NHS study centres across the UK. POPULATION: Nulliparous or multiparous women with a singleton pregnancy eligible for induction of labour. METHODS: Women were randomised to receive either misoprostol, initially 25 micrograms (50 micrograms in nulliparous women with Bishop score < or =4) followed by 25 micrograms after 4 and 8 hours, or dinoprostone, initially 3 mg followed by 3 mg after 6 hours. Clinical noninferiority of misoprostol was defined as an absolute difference between treatments of no more than 10% for the primary outcome. MAIN OUTCOME MEASURES: The number of vaginal deliveries achieved within 24 hours of labour induction. Maternal and fetal safety outcomes. RESULTS: A total of 626 women were randomised to misoprostol (n = 318) or dinoprostone (n = 308) treatment. The rate of vaginal deliveries achieved within 24 hours of induction did not significantly differ between the misoprostol and dinoprostone (43 versus 47%; 3.74% difference, 95% CI -3.58 to 11.05, respectively) treatment groups. The treatments were generally comparable for other secondary efficacy measures. Maternal and fetal adverse events were similarly distributed across the misoprostol and dinoprostone groups. CONCLUSIONS: Low-dose misoprostol is efficacious in cervical ripening and labour induction and demonstrates a similar fetal and maternal safety profile to dinoprostone.

Factors influencing maternal length of stay after giving birth in a UK hospital and the impact of those factors on bed occupancy.

On average, the length of time women remain in hospital after giving birth in the UK has deceased in recent years but most women are nevertheless admitted to a postnatal ward after childbirth. In this unique, prospective, observational study, we drew upon the expertise of caregivers on postnatal wards to reveal a wide range of obstetric, medical, neonatal and social problems that can lead to prolonged hospital stay. A woman's stay was likely to be increased by the greatest amount if her baby required specialised care but bed occupancy was more strongly influenced by the presence of obstetric complications because these were common. In this paper, we describe inpatient postnatal activity in detail and make recommendations for the safe and effective development of postnatal services.

Nuclear retinoid receptor expression in normal human endometrium throughout the menstrual cycle.

Previous work has shown that retinoic acid receptors (RARs) and retinoid X receptors (RXRs) are expressed in human endometrial epithelial and stromal cells. These nuclear receptors mediate the biological effects of retinoic acid, a vitamin A derivative which may have an important, though poorly characterized role in the functional differentiation of secretory epithelia. The aim of this study was to find out whether the expression of RAR and RXR mRNA in endometrial epithelial and stromal cells varies in relation to the menstrual cycle. The expression of RARs and RXRs was investigated by Northern blotting and, for stromal cells, there were no differences in expression of RAR-alpha, RAR-beta, RAR-gamma and RXR-alpha between the proliferative and secretory phases of the menstrual cycle. Similarly, for epithelial tissue, there were no significant differences between the proliferative and secretory phases with respect to the expression of RAR-alpha, RAR-gamma and RXR-alpha. However, RAR-beta was expressed at a 1.7-fold higher level in epithelial samples from the proliferative phase compared to the secretory phase. Overall, the levels of expression of RAR-alpha, RAR-beta and RAR-gamma were 1.7- to 4-fold higher in stromal cells compared to epithelial cells whereas RXR-alpha was expressed at a similar level in both cell types. We have previously suggested that retinoic acid has a role in endometrial differentiation or function which may be reflected by cyclical changes in intracellular retinoic acid levels. These data indicate that RARs and RXRs are expressed at a similar level throughout the menstrual cycle, with the possible exception of RAR-beta, implying that any menstrual cycle-related function of RARs in controlled by ligand availability rather than by changes in expression of the receptors.

Menstrual cycle related differences in the proliferative responses of cultured human endometrial stromal cells to retinoic acid.

Although ovarian-derived steroid hormones are central to the control of endometrial growth and secretory differentiation, all-trans retinoic acid, a derivative of vitamin A, may also play an important role. Since the retinoids can inhibit the proliferation of both fibroblasts and epithelial cells in experimental systems, we investigated whether the proliferation of endometrial stromal cells was inhibited by all-trans retinoic acid. A sensitive spectrophotometric assay was used to show that the proliferation rates of primary cultures of endometrial stromal fibroblasts varied with the timing of biopsy, and that all-trans retinoic acid inhibited the growth of late secretory phase cells but had no effect on cells sampled at other times. Furthermore, since the expression of mRNA encoding cellular retinoic acid binding protein type II decreases in endometrial stromal cells in the secretory phase, a rise in intracellular all-trans retinoic acid concentrations could be fundamental to the control of endometrial stromal cell proliferation and differentiation in vivo.

Variation in the expression of cellular retinoid binding proteins in human endometrium throughout the menstrual cycle.

Human endometrium is a glandular epithelial tissue with a substantial underlying stroma. Under the influence of ovarian steroids, endometrium undergoes a cyclical pattern of proliferation followed by secretory differentiation. Since retinoids promote the differentiation of many epithelia to secretory phenotypes they may be involved in controlling the secretory differentiation of human endometrial epithelium. Cytosolic binding proteins for retinol (cellular retinol binding protein) and retinoic acid (cellular retinoic acid binding protein) may play an important part in regulating the availability of retinoic acid to its nuclear receptors and we have therefore asked whether expression of mRNA for these proteins varies in relation to endometrial differentiation. In a series of 54 endometrial biopsies, both endometrial epithelial and stromal cells expressed mRNA for cellular retinol binding protein type I at a constant level throughout the menstrual cycle. Cellular retinoic acid binding protein type II was also expressed but the level of expression varied dramatically, being elevated in the proliferative phase and depressed during the secretory phase of the menstrual cycle in both epithelial and stromal cells. These data suggest that cytosolic binding proteins modulate the supply of retinoic acid to the nuclei of endometrial cells during the menstrual cycle and that retinoic acid is involved in the cyclical control of endometrial differentiation.