Carmen Regan

Prospective Evaluation of the Risk Conferred by Factor V Leiden and Thermolabile Methylenetetrahydrofolate Reductase Polymorphisms in Pregnancy

Factor V (FV) Leiden and thermolabile methylenetetrahydrofolate reductase (MTHFR) are 2 common polymorphisms that have been implicated in vascular thrombosis. We determined whether these mutations predicted an adverse outcome in pregnancy. Second, we looked for an interaction between these 2 mutations in patients with recurrent fetal loss or thrombosis in pregnancy. Primigravid subjects at their booking visit to the National Maternity Hospital (Holles Street, Dublin, Ireland) were screened for the polymorphisms. Thermolabile MTHFR and FV Leiden genotypes were detected by either restriction fragment length polymorphism or heteroduplex capillary chromatography. The carrier frequency of FV Leiden in the screened primigravid population was 2.7% (allele frequency 1.36%), all being heterozygous for the mutation. This value was lower than expected from previous studies in European populations. Forty-nine percent of the screened population (289 of 584) were heterozygous for thermolabile MTHFR, and 10.6% were homozygous (62 of 584). The frequency of the 2 polymorphisms was no higher in those who subsequently developed preeclampsia (n=12) or intrauterine growth retardation (n=9), and none of the screened population developed thrombosis. However, the frequency of FV Leiden was higher in patients who subsequently miscarried after the first trimester of pregnancy (allele frequency of 5.5%, P=0.0356). Among those positive for FV Leiden, 3 of 27 miscarried, compared with 24 of 572 of FV Leiden-negative patients (11% versus 4.2%). No interaction was found between the 2 mutations in the control or patient populations. In patients with a prior history of venous thrombosis, the carrier rate of FV Leiden was increased (4 of 33, allele frequency of 7.6%, P=0. 0115). In contrast, the carrier frequency for thermolabile MTHFR was no higher, and there was no interaction between the 2 mutations. Neither mutation occurred at a significantly higher frequency in patients with a prior history of recurrent fetal loss. In conclusion, FV Leiden is a risk factor for thrombosis in pregnancy and possibly for second-trimester miscarriage independent of thermolabile MTHFR. However, prospective analysis suggests that the risk conferred by FV Leiden is low in a primigravid population. The thermolabile MTHFR genotype was not implicated in any adverse outcome.

Reduced fetal exposure to aspirin using a novel controlled‐release preparation in normotensive and hypertensive pregnancies

Objectives To examine the fetal effects of a novel controlled‐release, low dose aspirin preparation in normal and hypertensive pregnancies.

The role of thromboxane A2 in the pathogenesis of intrauterine growth restriction associated with maternal smoking in pregnancy

BACKGROUND To examine the effect of maternal smoking in pregnancy on the production of two eicosanoids, thromboxane A(2) and prostacyclin I2, and their role in the pathogenesis of intrauterine growth restriction. METHODS Prospective case control study enrolled smoking and non-smoking women at ≤14 weeks gestation. Maternal urine samples were obtained at ≤14, 28 and 36 weeks. High performance liquid chromatography tandem mass spectrometry (LC-MS-MS) was used to quantify 11-dehydrothromboxane B(2) (TX-M) and 2,3 dinor-6-ketoprostaglandin F1α (PG-M), stable urinary metabolites of thromboxane A(2) and prostacyclin I2. Confirmation of the smoking status was performed by quantitation of urinary nicotine metabolites. Data was analysed using SPSS and Stata(®). RESULTS Thirty five were enrolled in the smoking group and 32 in the non-smoking group. Smoking resulted higher levels of TX-M at ≤14, 28 and 36 weeks gestation. There was no difference in PG-M at any gestational time point between the two groups. The median customised birthweight centile in the smoking group was 17.0 (0-78) compared to 55.5 (4-100) in the non-smoking group (P<0.001). A causal relationship between elevated TX-M and IUGR could not be established. CONCLUSIONS Maternal smoking in pregnancy is associated with altered eicosanoid production in favour of the vasoconstrictor thromboxane A(2) which occurs early in the first trimester.

Retrievable Inferior vena cava filters in pregnancy: Risk versus benefit?

OBJECTIVE Venous thromboembolism remains one of the leading causes of maternal mortality in the developed world. Retrievable inferior vena cava (IVC) filters have a role in the prevention of lethal pulmonary emboli when anticoagulation is contraindicated or has failed [1]. It is unclear whether or not the physiological changes in pregnancy influence efficacy and complications of these devices. The decision to place an IVC filter in pregnancy is complex and there is limited information in terms of benefit and risk to the mother. The objective of this study was to determine the efficacy and safety of these devices in pregnancy and to compare these with rates reported in the general population. STUDY DESIGN The aim of this study was report three recent cases of retrievable IVC filter use in pregnant women in our department and to perform a systematic review of the literature to identify published cases of filters in pregnancy. The efficacy and complication rates of these devices in pregnancy were estimated and compared to rates reported in the general population in a recent review [2]. Fishers exact test was used for statistical analysis. RESULTS In addition to our three cases, 16 publications were identified with retrievable IVC filter use in 40 pregnant women resulting in a total of 43 cases. There was no pulmonary embolus in the pregnant group (0/43) compared to 57/6291 (0.9%) in the general population. Thrombosis of the filter (2.3% vs. 0.9%, p = 0.33) and perforation of the IVC (7.0% vs 4.4%, p = 0.44) were more common in pregnancy compared to the general population but the difference was not statistically significant. Failure to retrieve the filter is more likely to occur in pregnancy (26% vs. 11%, p = 0.006) but this did not correlate with the type of device (p = 0.61), duration of insertion (p = 0.58) or mode of delivery (p = 0.37). CONCLUSION Data for retrievable IVC filters in pregnancy is limited and there may be a publication bias towards complicated cases. This study shows that the filter appears to protect against PE in pregnancy but the numbers are small. Complications such as filter thrombosis and IVC penetration appear to be higher in pregnancy but this difference is not statistically significant. It is not possible to retrieve the device in one out of every four pregnant women. This has implications in terms of long term risk of lower limb thrombosis and post thrombotic syndrome. The decision to use an IVC filter in pregnancy needs careful consideration by a multidisciplinary team. The benefit and risk assessment should be individualised and clearly outlined to the patient.

417. The impact of a tailored checklist on the quality of peripartum care delivered to women with inherited bleeding disorders.

Introduction Women with inherited bleeding disorders (IBD) can be at increased risk of bleeding peripartum and/or their babies are at risk of fetal or neonatal haemorrhage. The care they require is specific to the type of bleeding disorder they have and the plan for delivery requires multidisciplinary input. The World Health Organisation (WHO) has recommended new safety checklists as part of a drive to reduce medical errors and make healthcare safer. Communication is essential for optimal care. Developing an easy to follow bleeding disorder checklist draws the specialists information together and enables all healthcare professionals to quickly identify the care they must provide. Objectives The aim of the study was to identify any errors in care, to develop and implement a tailored bleeding disorder checklist, and to assess the impact of this on quality of care. Methods Fifty women with (or carriers of) an IBD were identified from a Maternal medicine service database and charts were reviewed. Quality of care indicators were assessed by chart review before and after the introduction of the checklist into clinical practice. Results When standards of care were compared before and after the introduction of the checklist: Haemostatic support was recommended for 19% of the group peripartum and given to 100%, compared to 29% and 100%. Maternal precautions were recommended in 42% and adopted in 78% compared to 43% and 100%. Fetal precautions were recommended in 86% and implemented in 94% compared to 89% and 100%. Cord bloods were advised in 58% and taken in 55% compared to 54% and 93%. Discussion Deficiencies in care were identified in this high risk group of women despite multidisciplinary peripartum planning of care. The development of a simple checklist that could be modified to meet the specific individuals needs resulted in improved quality and safety of care.