Antepartum dalteparin versus no antepartum dalteparin for the prevention of pregnancy complications in pregnant women with thrombophilia (TIPPS): a multinational open-label randomised trial.

BACKGROUND: Thrombophilias are common disorders that increase the risk of pregnancy-associated venous thromboembolism and pregnancy loss and can also increase the risk of placenta-mediated pregnancy complications (severe pre-eclampsia, small-for-gestational-age infants, and placental abruption). We postulated that antepartum dalteparin would reduce these complications in pregnant women with thrombophilia. METHODS: In this open-label randomised trial undertaken in 36 tertiary care centres in five countries, we enrolled consenting pregnant women with thrombophilia at increased risk of venous thromboembolism or with previous placenta-mediated pregnancy complications. Eligible participants were randomly allocated in a 1:1 ratio to either antepartum prophylactic dose dalteparin (5000 international units once daily up to 20 weeks' gestation, and twice daily thereafter until at least 37 weeks' gestation) or to no antepartum dalteparin (control group). Randomisation was done by a web-based randomisation system, and was stratified by country and gestational age at randomisation day with a permuted block design (block sizes 4 and 8). At randomisation, site pharmacists (or delegates) received a randomisation number and treatment allocation (by fax and/or e-mail) from the central web randomisation system and then dispensed study drug to the local coordinator. Patients and study personnel were not masked to treatment assignment, but the outcome adjudicators were masked. The primary composite outcome was independently adjudicated severe or early-onset pre-eclampsia, small-for-gestational-age infant (birthweight <10th percentile), pregnancy loss, or venous thromboembolism. We did intention-to-treat and on-treatment analyses. This trial is registered with ClinicalTrials.gov, number NCT00967382, and with Current Controlled Trials, number ISRCTN87441504. FINDINGS: Between Feb 28, 2000, and Sept 14, 2012, 292 women consented to participate and were randomly assigned to the two groups. Three women were excluded after randomisation because of ineligibility (two in the antepartum dalteparin group and one in the control group), leaving 146 women assigned to antepartum dalteparin and 143 assigned to no antepartum dalteparin. Some patients crossed over to the other group during treatment, and therefore for on-treatment and safety analysis there were 143 patients in the dalteparin group and 141 in the no dalteparin group. Dalteparin did not reduce the incidence of the primary composite outcome in both intention-to-treat analysis (dalteparin 25/146 [17·1%; 95% CI 11·4-24·2%] vs no dalteparin 27/143 [18·9%; 95% CI 12·8-26·3%]; risk difference -1·8% [95% CI -10·6% to 7·1%)) and on-treatment analysis (dalteparin 28/143 [19·6%] vs no dalteparin 24/141 [17·0%]; risk difference +2·6% [95% CI -6·4 to 11·6%]). In safety analysis, the occurrence of major bleeding did not differ between the two groups. However, minor bleeding was more common in the dalteparin group (28/143 [19·6%]) than in the no dalteparin group (13/141 [9·2%]; risk difference 10·4%, 95% CI 2·3-18·4; p=0·01). INTERPRETATION: Antepartum prophylactic dalteparin does not reduce the occurrence of venous thromboembolism, pregnancy loss, or placenta-mediated pregnancy complications in pregnant women with thrombophilia at high risk of these complications and is associated with an increased risk of minor bleeding. FUNDING: Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, and Pharmacia and UpJohn.

Building Research Capacity: Results of a Feasibility Study Using a Novel mHealth Epidemiological Data Collection System Within a Gestational Diabetes Population.

Public health researchers have traditionally relied on individual self-reporting when collecting much epidemiological surveillance data. Data acquisition can be costly, difficult to acquire, and the data often notoriously unreliable. An interesting option for the collection of individual health (or indicators of individual health) data is the personal smartphone. Smartphones are ubiquitous, and the required infrastructure is well-developed across Canada, including many remote areas. Researchers and health professionals are asking themselves how they might exploit increasing smartphone uptake for the purposes of data collection, hopefully leading to improved individual and public health. A novel smartphone-based epidemiological data collection and analysis system has been developed by faculty and students from the CEPHIL (Computational Epidemiology and Public Health Informatics) Lab in the Department of Computer Science at the University of Saskatchewan. A pilot feasibility study was then designed to examine possible relationships between smartphone sensor data, surveys and individual clinical data within a population of pregnant women. The study focused on the development of Gestational Diabetes (GDM), a transient condition during pregnancy, but with serious potential post-birth complications for both mother and child. The researchers questioned whether real-time smartphone data could improve the clinical management and outcomes of women at risk for developing GDM, enabling earlier treatment. The initial results from this small study did not show improved prediction of GDM, but did demonstrate that real-time individual health and sensor data may be readily collected and analyzed efficiently while maintaining confidentiality. Because the original version of the data collection software could only run on Android phones, this often meant the study participants were required to carry two phones, and this often meant the study phone was not carried, and therefore data not collected. The lessons learned will greatly inform future research.

Cardiac drug use in pregnancy: safety, effectiveness and obstetric implications.

Morbidity and mortality due to cardiovascular disease is increasing in pregnancy. The physiologic changes of normal pregnancy serve as a 'stress test' on the cardiovascular system. This may lead to the unmasking of a latent underlying cardiac condition or the new onset of maternal cardiovascular disease, with an attendant increase in adverse maternal and fetal outcomes. Some women with pre-existing cardiac conditions may be receiving medications that need to be altered during pregnancy owing to a risk of adverse effects on the developing fetus, but for most cardiac conditions, there are safe and effective treatment options. Women should be educated that abrupt discontinuation of cardiac medications during pregnancy usually poses a greater risk than the medications themselves, and a plan of judicious drug selection should be implemented (ideally prior to conception).