Botulinum Toxin Injection for Internal Rotation Contractures in Brachial Plexus Birth Palsy. A Minimum 5-Year Prospective Observational Study.

BACKGROUND: Brachial plexus birth palsy is frequently associated with internal rotation contractures of the shoulder as a result of muscle imbalance. The purpose of this study is to assess the effect of botulinum toxin A (BTX-A) injection in the subscapular (SC) muscle on external rotation and the need for tendon transfer for external rotation of the shoulder. METHODS: A prospective comparative study was performed including 15 consecutive patients treated with BTX-A and a historic control group of 67 patients with mean age 30 months (SD 10). The BTX-A injection (2 IU/kg body weight) was performed immediately following MRI under general anesthesia in the SC muscle. Passive external rotation, the need for tendon transfer surgery, glenohumeral deformity, and muscle degeneration were evaluated. The hazard ratio for no relapse of internal rotation contracture after BTX-A injection compared with no BTX-A injection was calculated. RESULTS: In the BTX-A group, the passive external rotation in adduction increased from -1 degree (95% CI, -10 to 8) to 32 degrees (95% CI, 17-46) at 3 months and 6 patients were indicated for surgery compared with a decline from -2 degrees (95% CI, -7 to 3) to -11 degrees (95% CI, -17 to -6) in the control group with 66 indications for surgery. At 5 years of follow-up, 10 patients in the BTX-A group were indicated for surgery with a hazard ratio of 4.0 (95% CI, 1.9 to 8.4). CONCLUSIONS: BTX-A injection in the SC muscle of brachial plexus birth palsy patients can reduce internal rotation contractures and subsequently the need for tendon transfer surgery. At 5 years of follow-up a relapse was seen in 67% of the patients treated with BTX-A. Because at MRI less SC degeneration was found in the good responders on BTX-A treatment, this group seems to be the best target group. Further research is needed on patient selection for BTX-A injection including glenohumeral deformity, SC degeneration, as well as doses of BTX-A to be used. LEVEL OF EVIDENCE: Level II-prospective comparative study.

Fetal exposure to HIV-1 alters chemokine receptor expression by CD4+T cells and increases susceptibility to HIV-1.

Absolute numbers of lymphocytes are decreased in uninfected infants born to HIV-1-infected women (HIV-1-exposed). Although the exact mechanism is unknown, fetal exposure to maternal HIV-1-infection could prime the immune system and affect T cell trafficking. We compared the expression of chemokine receptors on cord blood CD4(+) T cells from HIV-1-exposed children and healthy controls. At baseline CD4(+) T cells had a largely naïve phenotype. However, stimulation with cytokines resulted in an upregulation of inflammatory response-related chemokine receptors on CD4(+) T cells, with HIV-1-exposed infants having a significantly higher frequency of CD4(+) T cells expressing, in particularly Th2 associated chemokine receptors (CCR3 p < 0.01, CCR8 p = 0.03). Numbers of naive CCR7(+) CD4(+) T cells were reduced (p = 0.01) in HIV-1-exposed infants. We further assessed whether the inflammatory phenotype was associated with susceptibility to HIV-1 and detected higher levels of p24 upon in in vitro infection of stimulated CD4(+) T cells of HIV-1-exposed infants. In summary, fetal exposure to HIV-1 primes the immune system in the infant leading to an enhanced immune activation and altered T cell homing, with potential ramifications regarding T cell responses and the acquisition of HIV-1 as an infant.

Association of three different techniques to measure blood pressure in the first trimester with the development of hypertensive disorders of pregnancy.

OBJECTIVE: It is not known whether automated devices for measuring blood pressure perform better than conventional sphygmomanometry in predicting preeclampsia. This study compares two different automated devices with conventional sphygmomanometry for their association with development of preeclampsia or gestational hypertension. DESIGN: Prospective observational cohort study. SETTING: University hospital, Amsterdam, the Netherlands. POPULATION: 289 healthy normotensive women of whom 235 were nulliparous and 44 parous with preeclampsia in a previous pregnancy. METHODS: At 8-11 weeks of pregnancy, blood pressure was measured with two different automated devices (continuous finger arterial pressure waveform registration and ambulatory blood pressure monitoring) and with conventional sphygmomanometry. MAIN OUTCOME MEASURES: Preeclampsia and gestational hypertension. RESULTS: Blood pressure in the first trimester, as measured with all three methods, was significantly higher in women who developed preeclampsia or gestational hypertension. After adjustment for previous preeclampsia, the point estimate of the odds ratios for association with later preeclampsia for both automated devices were comparable and higher than for conventional sphygmomanometry; however, differences were not statistically significant. The odds ratio (95% confidence intervals) for every 1 mmHg pressure increase of mean arterial pressure was 1.08 (1.02-1.15) for sphygmomanometry, 1.17 (1.09-1.27) for finger arterial pressure waveform registration, and 1.17 (1.07-1.27) for ambulatory blood pressure monitoring. Results were comparable if preeclampsia and gestational hypertension were analyzed together. CONCLUSION: Blood pressure in the first trimester was associated with the development of hypertensive disorders of pregnancy. No significant differences were found between measurements by automatic devices compared with conventional sphygmomanometry.

Memory CD4(+)CCR5(+) T cells are abundantly present in the gut of newborn infants to facilitate mother-to-child transmission of HIV-1.

Despite potential clinical importance, target cells for mother-to-child transmission of HIV-1 have not yet been identified. Cord blood-derived CD4(+) T cells are largely naive and do not express CCR5, the mandatory coreceptor for transmitted HIV-1 R5 strains in infants. In the present study, we demonstrate that in the human fetal and infant gut mucosa, there is already a large subset of mucosal memory CD4(+)CCR5(+) T cells with predominantly a Th1 and Th17 phenotype. Using next-generation sequencing of the TCRß chain, clonally expanded T cells as a hallmark for memory development predominated in the gut mucosa (30%), whereas few were found in the lymph nodes (1%) and none in cord blood (0%). The gut mucosal fetal and infant CD4(+) T cells were highly susceptible to HIV-1 without any prestimulation; pol proviral DNA levels were similar to infected phytohemagglutinin-stimulated adult PBMCs. In conclusion, in the present study, we show that extensive adaptive immunity is present before birth and the gut mucosa is the preferential site for memory CD4(+) T cells. These CD4(+)CCR5(+) T cells in the infant mucosa provide a large pool of susceptible cells for ingested HIV-1 at birth and during breastfeeding, indicating a mucosal route of mother-to-child transmission that can be targeted in prevention strategies.

Hcv coinfection, an important risk factor for hepatotoxicity in pregnant women starting antiretroviral therapy.

OBJECTIVES: This retrospective cohort study evaluated the risk of hepatotoxicity in HIV-1 positive pregnant and non-pregnant women starting combined ART. METHODS: Data were used from the ATHENA observational cohort. The study population consisted of HIV-1 infected, therapy naïve, pregnant and non-pregnant women, followed between January 1997 and February 2008. Demographic, treatment and pregnancy related data were collected. Risk of hepatotoxicity was determined using univariate and multivariate logistic regression. Analyses were adjusted for age, region of origin, baseline HIV-RNA levels and CD4 cell counts, cART regimen and hepatitis B and C coinfection. ALT and AST values of more than 5 times ULN were considered as hepatotoxicity. RESULTS: Four-hundred and twenty-five pregnant and 1121 non-pregnant women were included. Independent risk factors of hepatotoxicity in all women were the presence of detectable HCV RNA (OR 5.48, 95% CI 2.25-13.38, p<0.001) and NVP use (OR 2.63, 95% CI 1.54-4.55, p<0.001). Stratified for pregnancy, the adjusted risk of hepatotoxicity was significantly associated with HCV coinfection only during pregnancy (OR 23.53, 95% CI 4.69-118.01, p<0.001). NVP use is related to hepatotoxicity in pregnant (OR 5.26, 95% CI 1.61-16.67, p<0.005) as well as in non-pregnant women (OR 2.13, 95% CI 1.11-4.00, p=0.02). CONCLUSION: HCV coinfection and NVP use are associated with a higher risk of cART induced hepatotoxicity in pregnant women.

Complications of the 2009 influenza A/H1N1 pandemic in pregnant women in The Netherlands: a national cohort study.

The 2009 influenza A/H1N1 pandemic caused an increase in complications in pregnant women. To be well prepared for a next pandemic, we investigated the obstetric and maternal complications of this pandemic. In our national cohort of 59 pregnant women who were admitted to the hospital, no major complications apart from preterm birth and admission to the neonatal intensive care unit were observed. Although the small size of this study precludes us drawing any definitive conclusions, comparing our results with those in other countries suggests that the influenza A/H1N1 pandemic had a relatively benign course in pregnant women in The Netherlands.

Utilizing new evidence in the prevention of recurrent preterm birth.

OBJECTIVE: Treatments that have proven to be effective in large randomized controlled trials are implemented in clinical practice at varying rates. We measured to what extent new and established strategies were applied to prevent recurrent preterm birth in the Netherlands. METHODS: In two academic hospitals, two non-academic teaching hospitals and two non-academic, non-teaching hospitals, we reviewed charts of all women who had delivered in 2006 and at that time had a history of spontaneous preterm birth before 34 weeks. We compared the application of preventive treatments between different types of hospitals. RESULTS: Ninety-one records were identified. In academic centers, screening for bacterial vaginosis and progesterone treatment were applied more often than in other centers (49 vs. 14%, p-value 0.001 and 63 vs. 22%, p-value <0.001, respectively). Cervical length measurement was applied more often in non-academic hospitals (58 vs. 39%, p-value 0.07), but with fewer measurements per patient (average of 3.3 vs. 5.8). CONCLUSION: In the management of women with a history of preterm birth, there is large practice variation. Relatively new treatments such as progesterone injections and screening for bacterial vaginosis are applied more frequently in academic centers, whereas cervical length measurement is more often performed in non-academic hospitals.

Antenatal screening for HIV, hepatitis B and syphilis in the Netherlands is effective.

BACKGROUND: A screening programme for pregnant women has been in place since the 1950s in the Netherlands. In 2004 universal HIV screening according to opting out was implemented. Here, we describe the evaluation of the effectiveness of antenatal screening in the Netherlands for 2006-2008 for HIV, hepatitis B virus (HBV) and syphilis in preventing mother-to-child transmission, by using various data sources. METHODS: The results of antenatal screening (2006-2008) were compared with data from pregnant women and newborns from other data sources. RESULTS: Each year, around 185,000 pregnant women were screened for HIV, HBV and syphilis. Refusal rates for the screening tests were low, and were highest (0.2%) for HIV. The estimated annual prevalence of HIV among pregnant women was 0.05%.Prior to the introduction of screening, 5-10 children were born with HIV annually After the introduction of screening in 2004, only 4 children were born with HIV (an average of 1 per year). Two of these mothers had become pregnant prior to 2004; the third mother was HIV negative at screening and probably became infected after screening; the fourth mother's background was unknown. Congenital syphilis was diagnosed in fewer than 5 newborns annually and 5 children were infected with HBV. In 3 of these, the mothers were HBeAg positive (a marker for high infectivity). We estimated that 5-10 HIV, 50-75 HBV and 10 syphilis cases in newborns had been prevented annually as a result of screening. CONCLUSIONS: The screening programme was effective in detecting HIV, HBV and syphilis in pregnant women and in preventing transmission to the child. Since the introduction of the HIV screening the number of children born with HIV has fallen dramatically. PREVIOUS PUBLICATION: [Translation from: 'Prenatale screening op hiv, hepatitis B en syphilis in Nederland effectief', published in 'The Dutch Journal of Medicine ' (NTVG, in Dutch)].

The functions of microparticles in pre-eclampsia.

Pre-eclampsia (P-EC), a heterogenic multisystem disorder characterized by hypertension and proteinuria, usually develops in the second half of pregnancy. The incidence is 2 to 5%, and P-EC is therefore a major cause of maternal and perinatal morbidity and mortality. Although the exact etiology is unknown, placental factors released into the maternal circulation lead to systemic maternal inflammation and endothelial dysfunction. Growing evidence indicates that placenta-derived microparticles, best known as syncytiotrophoblast microparticles (STBM), are important among these factors. This review provides an overview of the presence and function(s) of STBM and other cell-derived microparticles and exosomes.

The comparison of the performance of two screening strategies identifying newly-diagnosed HIV during pregnancy.

BACKGROUND: In the Netherlands, a non-selective opt-out instead of a selective opt-in antenatal HIV screening strategy was implemented in 2004. In case of infection, screening was followed by prevention of mother-to-child-transmission (PMTCT). We compared the performance of the two strategies in terms of detection of new cases of HIV and vertical transmission. METHODS: HIV-infected pregnant women were identified retrospectively from the Dutch HIV cohort ATHENA January 2000 to January 2008. Apart from demographic, virological and immunological data, the date of HIV infection in relation to the index pregnancy was established. Separately, all infants diagnosed with HIV born following implementation of the screening program were identified by a questionnaire via the paediatric HIV centres. RESULTS: 162/481 (33.7%) HIV-positive pregnant women were diagnosed with HIV before 2004 and 172/214 (80.3%) after January 2004. Multivariate analysis showed an 8-fold (95% confidence interval 5.47-11.87) increase in the odds of HIV detection during pregnancy after the national introduction of the opt-out strategy. Still, three children born during a 5-year period after July 2004 were infected due to de novo infection in pregnancy. CONCLUSIONS: Implementation of a nation-wide screening strategy based upon non-selective opt-out screening followed by effective PMTCT appeared to detect more HIV-infected women for the first time in pregnancy and to reduce vertical transmission of HIV substantially. Nonetheless, still few children are infected because of maternal infection after the first trimester. We propose the introduction of partner screening on HIV as part of the antenatal screening strategy.

Does physical activity in leisure time early in pregnancy reduce the incidence of preeclampsia or gestational hypertension?

OBJECTIVE: Assessment of the association of physical activity in leisure time with preeclampsia and gestational hypertension in nulliparous women. DESIGN: Population based prospective cohort study. SETTING: Amsterdam, The Netherlands. POPULATION: All pregnant women in Amsterdam between January 2003 and March 2004 who were nulliparous with a singleton pregnancy and who delivered after 24 weeks. DESIGN: At their first prenatal care visit, women were invited to fill out a questionnaire with sociodemographic and psychosocial variables. Physical activity in leisure time in the past week was measured using questions about walking, cycling, playing sports and other activities in leisure time. The amount of minutes and intensity of each activity was studied using four categories: no, low, moderate or high activity. By using multivariate logistic regression, we adjusted for sociodemographic and medical confounders. MAIN OUTCOME MEASURES: Incidence of preeclampsia and gestational hypertension. Results. A total of 12,377 women were invited with a response rate of 67%; 3,679 nulliparous women were included. The incidence of preeclampsia and gestational hypertension was 3.5% and 4.4%, respectively. The amount of time or intensity of physical activity in leisure time was not associated with a difference in risk of preeclampsia or gestational hypertension. CONCLUSION: Physical activity in leisure time early in pregnancy does not reduce the incidence of preeclampsia or gestational hypertension in an unselected population of nulliparous women.

Limited accuracy of the hyperbaric index, ambulatory blood pressure and sphygmomanometry measurements in predicting gestational hypertension and preeclampsia.

OBJECTIVE: The aim of this study was to validate the hyperbaric index (HBI) for first trimester prediction of preeclampsia and gestational hypertension. METHODS: Participants were low-risk and high-risk nulliparous women and high-risk multiparous women, and were recruited between April 2004 and June 2006. At a gestational age of 9 weeks (range 8-11 weeks), blood pressure (BP) was measured first by sphygmomanometry and thereafter by ambulatory BP measurement (ABPM) for 48 h. The first 90 low-risk women who had an uneventful pregnancy formed the reference group for calculation of a time-specified tolerance interval with 90% confidence limits. In the validation group, consisting of the remaining women, the HBI was calculated as the time-specified BP excess over this tolerance limit for SBP, DBP and mean arterial pressure. RESULTS: The validation group contained 101 women. Fifteen women developed preeclampsia and 13 developed gestational hypertension. For preeclampsia, the maximum HBI had the best predictive capacity with a sensitivity of 73% and a specificity of 86%. However, the difference with standard ABPM measurement or sphygmomanometry was small with a sensitivity between 75 and 73% and a specificity between 86 and 95%. The predictive efficacy for gestational hypertension was poor with all methods (sensitivity between 54 and 77%, specificity between 41 and 78%). CONCLUSION: Standardized sphygmomanometry, ABPM measurement and the HBI calculated from 48-h ABPM had a comparable, restricted predictive efficacy. The high predictive value of HBI as observed in earlier studies could not be reproduced.

Use of progesterone treatment for the prevention of recurrent preterm birth: identification of obstacles to change.

Progesterone treatment has proven to be effective in preventing recurrent preterm birth. The use of progesterone varies widely between different obstetric clinics in the Netherlands. The study aimed to identify factors that hamper or facilitate the use of progesterone to create an implementation strategy. A Web-based survey was developed containing questions on sociopolitical factors, organizational factors, knowledge, and attitude. This survey was spread among 212 gynecologists, 203 midwives, and 130 women with a recent preterm birth. Response rates were 46% for gynecologists, 57% for midwives, and 78% for patients. Twenty-five percent of gynecologists were prescribing progesterone, 21% of midwives would recommend progesterone, and 54% of patients were willing to undergo treatment in future pregnancies. Specific factors hampering implementation for gynecologists were working in nonteaching hospitals and absence of progesterone treatment in local protocols. For midwives and patients, unfamiliarity with progesterone was the most notable finding. The major reason for failure of implementation of progesterone treatment to prevent recurrent preterm birth is absence of this treatment in protocols and lack of familiarity with this treatment in midwives and patients. This may be overcome through adjustment of clinical protocols on regional and national levels.

[Treatment of HIV-infected pregnant women: prevention of virus transmission and adverse effects in mother and child]. / Behandeling van hiv-geïnfecteerde zwangeren: preventie van virustransmissie en bijwerkingen bij moeder en kind.

Without intervention, the probability of HIV transmission from mother to child varies from less than 10% to over 60%, dependent on the quantity of freely circulating HIV in the plasma. The prevention of HIV transmission from mother to child is based on the perinatal administration of a combination of antiretroviral drugs (highly active antiretroviral therapy; HAART) to both mother and child. The value of elective caesarean section along with an effective treatment with HAART during the pregnancy is very limited. Exclusive breastfeeding does not lead to a higher HIV transmission than bottle-feeding, but this effect does not lead to a successful strategy. As prophylactic treatment with HAART is widely used, it can be assumed that, in general, the use of HAART during pregnancy is relatively safe. Whether the same is true for the use of specific, and often newer drugs, is frequently not known due to the scarcity of data. For pregnant women it is important to carefully monitor adverse effects such as hepatotoxicity during the first few weeks of treatment. The most important adverse effect for the pregnancy appears to be premature birth. Yet this only occurs if HAART has to be used throughout the entire pregnancy. In the neonate mitochondrial toxicity and haematological effects can occur. These appear to be clinically insignificant but longer term effects cannot be excluded. On the basis of the available long-term safety data for children, no single antiretroviral drug has proven safety.

Leukocyte activation and circulating leukocyte-derived microparticles in preeclampsia.

PROBLEM: Preeclampsia shows characteristics of an inflammatory disease including leukocyte activation. Analyses of leukocyte-derived microparticles (MP) and mRNA expression of inflammation-related genes in leukocytes may establish which subgroups of leukocytes contribute to the development of preeclampsia. METHOD OF STUDY: Blood samples were obtained from preeclamptic patients, normotensive pregnant and non-pregnant controls. sL-selectin and elastase were measured by ELISA. mRNA was isolated from leukocytes and gene expression was determined by multiplex ligation-dependent probe amplification (MLPA). MP were characterized by flow cytometry. RESULTS: Altered concentrations of sL-selectin and elastase confirmed leukocyte activation in preeclampsia. These leukocytes showed up-regulation of Nuclear Factor of Kappa light chain gene enhancer in B cells inhibitor (NFkappaB-1A) and cyclin-dependent kinase inhibitor (CDKN)-1A compared with normotensive pregnant women. Interleukin-1 Receptor Antagonist (IL-1RA) and tumor necrosis factor (TNF)-R1 were increased compared with those in non-pregnant controls. Monocyte-derived MP were elevated in preeclamptic patients compared with pregnant women. The numbers of cytotoxic T-cell-derived and granulocyte-derived MP were elevated compared with those of non-pregnant women. CONCLUSION: Leukocytes are activated in preeclampsia. A pro-inflammatory gene expression profile is not prominent, although differences in mRNA expression can be detected. Increased levels of particular subsets of leukocyte-derived MP reflect activation of their parental cells in preeclampsia.

Brain ultrasonography findings in neonates with exposure to cocaine during pregnancy.

BACKGROUND: Cocaine exposure during pregnancy has been reported to have detrimental effects on the fetus. OBJECTIVE: To describe the findings on cranial ultrasonography (CUS) as part of a neonatal screening programme for exposed neonates. MATERIALS AND METHODS: The study was a semiprospective analysis of a 12-year cohort of neonates born to mothers who had used cocaine during their pregnancy and who had follow-up according to a strict clinical protocol. RESULTS: In total, 154 neonates (78 boys, 76 girls) were included, of whom 29 (19%) were born preterm, and 125 (81%) were born full-term. Abnormalities on CUS were seen in 37 neonates (24%; 95% CI 18-31%). The abnormalities were classified as minor in 20 (13%; 95% CI 9-19%) and mildly abnormal in 17 (11%; 95% CI 7-17%). None of the infants showed severe abnormalities. The abnormalities were not associated with the duration or maximum amount of cocaine use during pregnancy. CONCLUSION: None of the infants had severe abnormalities. Detected abnormalities were not correlated with the duration or maximum amount of cocaine use. Given these findings, we feel that routine cranial ultrasonography in this population is not warranted.

Changes in microparticle numbers and cellular origin during pregnancy and preeclampsia.

BACKGROUND: Microparticles (MP) are pro-coagulant vesicles derived from various cells. Evidence is accumulating that MP are of pathophysiological relevance in autoimmune, cardiovascular, and thromboembolic diseases and inflammatory disorders. Therefore, their role in the development of preeclampsia was investigated and MP from preeclamptic patients influenced endothelial-dependent vasodilatation. Knowledge about changes in circulating MP numbers during pregnancy and preeclampsia is lacking. We determined this longitudinally and investigated whether these numbers related to the severity of preeclampsia. METHODS: Samples were obtained from pregnant women and preeclamptic patients during pregnancy and postpartum. MP were isolated and studied by flow cytometry. RESULTS: During pregnancy, MP were decreased at 12 weeks gestation and then returned to postpartum values. In patients with preeclampsia, MP numbers were reduced at 28 and 36 weeks (both p = 0.04). Monocyte-derived MP were elevated in preeclampsia at 28 (p = 0.007), 32 (p = 0.02), and 36 weeks (p = 0.01), as were erythrocyte-derived MP at 28 weeks (p = 0.04). Placenta-derived MP increased in pregnancy and preeclampsia. During pregnancy, a correlation was present between placenta-derived MP and systolic blood pressure (r = 0.33, p = 0.015). No other correlations were found. CONCLUSIONS: During pregnancy, numbers of MP initially decrease and subsequently normalize. Placenta-derived MP increase, possibly because of placental growth. In preeclampsia, reduced numbers of PMP are due to decreased platelet counts. Increased numbers of monocyte-derived MP reflect monocyte activation, which may be an expression of the systemic inflammation in preeclampsia. Lack of correlation between numbers of MP and severity of preeclampsia suggests that MP numbers alone do not explain the reported vascular effects of MP.

Progesterone for the prevention of preterm birth in women with multiple pregnancies: the AMPHIA trial.

BACKGROUND: 15% of multiple pregnancies ends in a preterm delivery, which can lead to mortality and severe long term neonatal morbidity. At present, no generally accepted strategy for the prevention of preterm birth in multiple pregnancies exists. Prophylactic administration of 17-alpha hydroxyprogesterone caproate (17OHPC) has proven to be effective in the prevention of preterm birth in women with singleton pregnancies with a previous preterm delivery. At present, there are no data on the effectiveness of progesterone in the prevention of preterm birth in multiple pregnancies. METHODS/DESIGN: We aim to investigate the hypothesis that 17OHPC will reduce the incidence of the composite neonatal morbidity of neonates by reducing the early preterm birth rate in multiple pregnancies. Women with a multiple pregnancy at a gestational age between 15 and 20 weeks of gestation will be entered in a placebo-controlled, double blinded randomised study comparing weekly 250 mg 17OHPC intramuscular injections from 16-20 weeks up to 36 weeks of gestation versus placebo. At study entry, cervical length will be measured. The primary outcome is composite bad neonatal condition (perinatal death or severe morbidity). Secondary outcome measures are time to delivery, preterm birth rate before 32 and 37 weeks, days of admission in neonatal intensive care unit, maternal morbidity, maternal admission days for preterm labour and costs. We need to include 660 women to indicate a reduction in bad neonatal outcome from 15% to 8%. Analysis will be by intention to treat. We will also analyse whether the treatment effect is dependent on cervical length. DISCUSSION: This trial will provide evidence as to whether or not 17OHPC-treatment is an effective means of preventing bad neonatal outcome due to preterm birth in multiple pregnancies. TRIAL REGISTRATION: Current Controlled Trials ISRCTN40512715.

Microparticle-associated P-selectin reflects platelet activation in preeclampsia.

Platelet activation in preeclampsia is reflected by elevated levels of platelets exposing P-selectin. In plasma, a non-cell bound (soluble) form of P-selectin is present. Elevated levels of this soluble form have been reported in preeclampsia. Plasma P-selectin may consist of two fractions: microparticle (MP)--associated P-selectin and non-MP--associated P-selectin. In the present cross-sectional study, we investigated to which extent plasma P-selectin is MP--associated and whether such MP are elevated in preeclamptic patients. Preeclamptic patients (n=10) were matched with normotensive pregnant women (n=10) and non-pregnant controls (n=10). Plasma P-selectin was measured by ELISA. MP were isolated, double labelled with anti-CD61 (GPIIIa) and anti-CD62P (P-selectin) and subsequently analyzed with flowcytometry. Plasma P-selectin concentration was elevated in preeclamptic patients compared to non-pregnant controls (p=0.007), but not compared to normotensive pregnant women (p=0.210). Plasma P-selectin is partially MP--associated (3-5%). In pregnancy, the fraction of P-selectin exposing platelet-derived MP (PMP) (10.9%) was increased compared to non-pregnant controls (8%). This fraction further increased in preeclamptic patients (15.4%), and significantly differed from normotensive pregnant women (p=0.02). A minor fraction of plasma P-selectin is associated with PMP. The fraction of PMP exposing P-selectin is increased in preeclamptic patients and to a lesser extent in normotensive pregnancy. Because MP associated P-selectin exclusively originates from platelets, this fraction indicates platelet activation. Platelet activation is prominent in preeclampsia and this study proves that at least a part of the plasma P-selectin originates from platelets.