A Multicentre Study of Thromboprophylaxis in Pregnancy.

Venous thromboembolism (VTE) is a leading cause of maternal mortality. The risk increases with increasing maternal age, mode of delivery and medical co-morbidities. Thromboprophylaxis with low molecular weight heparin (LMWH) has been shown to be both safe and efficacious. The aim of this study was to prospectively investigate the incidence of maternal risk factors in pregnant women admitted to hospital, to calculate their VTE risk status and to investigate if they were receiving appropriate thromboprophylaxis. All patients admitted to the participating hospitals on the day of investigation were assessed for risk of VTE on the basis of hospital chart review. Five Hundred and forty women were recruited from 16 hospitals. Almost 32% (31.7%) were receiving thromboprophylaxis with LMWH. Just under 80% of patients were on the correct thromboprophylaxis strategy as defined by the RCOG guideline but 49% were under-dosed. The odds of receiving appropriate thromboprophylaxis were significantly increased if the woman was >35 years 0or with parity>3.

Implementation of thromboprophylaxis guidelines.

Venous thromboembolism (VTE) remains one of the leading direct causes of maternal death. Risk factors for VTE and prophylaxis guidelines have been highlighted by the Royal College of Obstetricians and Gynaecologists (RCOG). A cross sectional study was completed in Cork University Maternity Hospital (CUMH) to determine pattern of VTE risk and compliance with 2004 RCOG guidelines. 364 women's charts were reviewed. Forty percent (n = 145) were at risk for VTE, 69% (n = 100) of these received thromboprophylaxis but only 54% (n = 54) received the correct weight adjusted dose. Three of four morbidly obese women in this study received recommended thromboprophylaxis but none at the appropriate dose. Only 67% (n = 245) had a recorded body mass index (BMI). Increased BMI is a significant risk factor for VTE and should be measured and recorded at the booking visit. Awareness of the risks for VTE and the need for appropriate dosing should be improved.

The PAI-1 4G/5G polymorphism is not associated with an increased risk of adverse pregnancy outcome in asymptomatic nulliparous women.

BACKGROUND: Plasminogen activator inhibitor type 1 (PAI-1) is an important regulator of fibrinolysis. A common deletion polymorphism that results in a sequence of 4G instead of 5G in the promoter region of the gene is associated with a small increase in the risk of venous thromboembolism. Its potential association with adverse pregnancy events remains controversial. OBJECTIVE: We aimed to assess the impact of the 4G PAI-1 polymorphism on pregnancy outcomes in women who had no prior history of adverse pregnancy outcomes or personal or family history of venous thromboembolism. PATIENTS/METHODS: This study represents a secondary investigation of a prior prospective cohort study investigating the association between inherited thrombophilias and adverse pregnancy events in Australian women. Healthy nulliparous women were recruited to this study prior to 22 weeks gestation. Genotyping for the 4G/5G PAI-1 gene was performed using Taqman assays in an ABI prism 7700 Sequencer several years after the pregnancy was completed. Pregnancy outcome data were extracted from the medical record. The primary outcome was a composite comprising development of severe pre-eclampsia, fetal growth restriction, major placental abruption, stillbirth or neonatal death. RESULTS: Pregnancy outcome data were available in 1733 women who were successfully genotyped for this polymorphism. The primary composite outcome was experienced by 139 women (8% of the cohort). Four hundred and fifty-nine women (26.5%) were homozygous for the 4G deletion polymorphism, while 890 (51.4%) were heterozygous. Neither homozygosity nor heterozygosity for the PAI-1 4G polymorphism was associated with the primary composite outcome (homozygous OR = 1.30, 95% CI = 0.81-2.09, P = 0.28, heterozygous OR = 0.84, 95% CI = 0.53-1.31, P = 0.44) or with the individual pregnancy complications. CONCLUSION: The PAI-1 4G polymorphism is not associated with an increase in the risk of serious adverse pregnancy events in asymptomatic nulliparous women.

The management of reduced fetal movements in an uncomplicated pregnancy at term: results from an anonymous national online survey in the Republic of Ireland.

There is currently inconsistent evidence and clinical guidance on how to best manage a pregnancy complicated by reduced fetal movements. This novel, web-based, anonymous questionnaire evaluated 96 assessment and management approaches from doctors working in obstetrics in the Republic of Ireland who were presented with a clinical scenario of a primigravida concerned about reduced fetal movements at 39+3 weeks' gestation. This study identified a lack of clinical practice guidelines available in maternity hospitals in the Republic of Ireland. We demonstrated that almost all clinicians applied more than one assessment method and that most incorporated a cardiotocograph into their assessment. There was a low uptake of simple symphysio-fundal height measurement and high usage of kickcharts. The minority of clinicians admitted or induced their patients. This survey identified the need for national and international guidelines to ensure safe antepartum care and delivery.

Prevalence of suboptimal vitamin D status during pregnancy.

Low maternal vitamin D status has been associated with reduced intrauterine long bone growth and shorter gestation, decreased birth weight, as well as reduced childhood bone-mineral accrual. Despite data from other countries indicating low maternal vitamin D status is common during pregnancy, there is a dearth of information about vitamin D status during pregnancy in the Irish female population. Therefore, we prospectively assessed vitamin D nutritive status and the prevalence of suboptimal vitamin D status in a cohort of Irish pregnant women. The mean (SD) daily intake of vitamin D by the group of pregnant women was 3.6 (1.9) microg/day. None of the women achieved the recommended daily vitamin D intake value for Irish pregnant women (10 microg/day). Taking all three trimesters collectively, 14.3-23.7% and 34.3-52.6% of Irish women had vitamin D deficiency (serum 25 (OH) D <25 nmol/l) and insufficiency (serum 25 (OH) D 25-50 nmol/l), respectively during pregnancy. Both the levels of serum 25 (OH) D and the prevalence of vitamin D deficiency/adequacy were dramatically influenced by season, with status being lowest during the extended winter period and best during the extended summer period. These findings show that inadequate vitamin D status is common in Irish pregnant women.

Timing of birth related to obstetric practice and neonatal outcome.

Several studies have reported time of birth is associated with differences in obstetric practice. We investigated the relationship between timing of birth and obstetric and neonatal outcomes, to help plan working patterns under European Working Time Directive (EWTD) legislation. This was a retrospective observational study undertaken in a tertiary-level university teaching hospital. Data were derived from the labour ward register of births for all women who delivered after 24weeks gestation in 2004. Births during on-call hours refer to those that occurred at weekends and after 1630 and before 0830 on weekdays. The majority of infants, 67.3%, were born in on-call hours. Infants were more likely to be delivered by ventouse(p<0.0001), but there was no difference in caesarean section(CS) rates. 83.0% of operative deliveries performed for failure to advance in the second stage of labour took place in on-call hours, as did 77.5% of emergency CS for fetal distress. 38.9% of infants born during on-call hours on weekdays followed induced labours, compared to 24.7% of births at weekends and 17.7% of births in non on-call hours(p<0.001), while 80.0% of deliveries by emergency CS after induction occurred during on-call hours. The majority of perinatal deaths occurred among infants born during on-call hours, even when excluding congenital malformations, and most infants with low Apgar scores were born during on-call hours. Complicated deliveries were more likely to occur in on-call hours. This study confirms previous reports that time of birth impacts on neonatal outcome. Increased demands on staff working out-of-hours have implications for healthcare, staffing and implementation of new working hours under EWTD legislation.

The decline of laparoscopic sterilisation.

Female sterilisation is an extensively used method of contraception all over the world but there appears to be a decline in the performance of this procedure in Ireland. There also appears to be an increased uptake of safe, long-acting contraceptive alternatives. We set out to establish the extent of the decline of laparoscopic sterilisation and to explore possible explanations. Data for female sterilisation from Ireland was obtained from the Hospital In-Patient Enquiry Scheme (HIPE) section of the Economic and Social Research Institute for the years 1999 to 2004. Recent sales figures for long acting reversible contraceptives, specifically the levo-norgestrel-loaded intrauterine system (LNG-IUS) (Mirena) and the etonogestrel implant (Implanon) were also obtained. Laparoscopic tubal ligations reduced from 2,566(1999) to 910 (2004). In the corresponding period the use of Mirena coils increased from 4,840 (1999) to 17,077 (2004).

Ascertaining women's preferred mode of address and preferred choice of title during pregnancy and childbirth.

To determine how women in pregnancy would like to be addressed and to ascertain their preferred choice of title during pregnancy. A questionnaire was administered to 925 antenatal women. Midwifery and medical staff (183) were invited to respond to a similar questionnaire. The response rate was 71.2% from the survey of pregnant women. The vast majority (82.1%) preferred to be addressed by their first name. Women were in favour of being called 'patient' (32.8%) as their first choice. The staff survey yielded a response rate of 77%. The majority (81.8%) of health professionals preferred to address women by their first name. 'Mother' (28.7%) was the most popular first choice. We conclude that women in pregnancy do have a preference on how they would like to be addressed and this is predominantly by first name. Health professionals also prefer to call pregnant women by their first name. The term 'patient' was the most popular first choice of title of women in pregnancy but the term 'mother' was the preferred choice of the health professionals. Medical staff were more likely to choose 'patient' than midwives.

The relation between maternal work, ambulatory blood pressure, and pregnancy hypertension.

STUDY OBJECTIVE: The purpose of the study was to determine the relations between maternal work, ambulatory blood pressure in mid-pregnancy, and subsequent pregnancy outcome. DESIGN: Data were studied on 933 healthy normotensive primigravidas who had been enrolled into a study on the predictive value of ambulatory blood pressure measurement performed between 18 and 24 weeks gestation. They were classified into three groups depending on whether they were at work (working group, n=245), not working (not working group, n=289), or normally employed but chose not to work (ENK group, n=399), on the day monitoring was performed. SETTING: The Rotunda Hospital (a large maternity hospital), Dublin, Ireland. MAIN RESULTS: Adjusted for age, body mass index, smoking, drinking, and marital status, women at work had higher mean daytime systolic (p<0.01) and diastolic (p<0.01) and 24 hour systolic pressures (p=0.03) compared with those not working. The rate of subsequent development of pre-eclampsia was significantly higher (odds ratio 4.1, 95% CI 1.1 to 15.2, p=0.03) among those at work compared with those not working. The association between pre-eclampsia and maternal work remained significant (odds ratio 5.5, 95% CI 1.1 to 27.8, p=0.04) even after allowing for the confounding factors of age, smoking, body mass index, and marital status. When daytime systolic and diastolic blood pressure were added to the regression analysis the risk ratios for pre-eclampsia remained high but did not quite reach statistical significance (odds ratio 4.7, 0.90 to 24.8, p=0.066). Birth weight and placental weight were not predicted by work status or blood pressure. CONCLUSIONS: A significant independent relation was found between maternal work and ambulatory blood pressure levels in mid-pregnancy. In addition, it was found that maternal work was significantly associated with the subsequent development of pre-eclampsia

Optimizing stent expansion with new stent delivery systems.

OBJECTIVES: The purpose of this study was to assess whether the newer stent delivery systems provide a stented lumen cross-sectional area (CSA) that is equal to the delivery balloon nominal dimensions. BACKGROUND: First generation stents were often not adequately expanded with their delivery system and frequently required higher pressure or a larger balloon after deployment. Newer stents were designed to optimize expansion with noncompliant, high-pressure balloons provided as the delivery systems. METHODS: Intravascular ultrasound (IVUS) was used to evaluate 38 stents in 32 patients after deployment at 14 to 16 atm with their delivery balloon system. Minimum stent lumen CSA and stent minimum lumen diameter (MLD) were measured by IVUS imaging. The manufacturer's expected stent diameter was defined as the balloon diameter measured by the company at the maximum pressure used. The manufacturer's expected stent area was calculated based on the manufacturer's expected stent diameter. RESULTS: The MLD (2.5 +/- 0.5 mm) and minimum stent CSA (6.0 +/- 1.7 mm(2)) by IVUS were significantly smaller than the manufacturer's expected stent diameter (3.5 +/- 0.4 mm) and area (9.5 +/- 1.9 mm(2)) (p < 0.0001, respectively). The mean MLD by IVUS was 72 +/- 8% of the expected stent diameter, and the mean minimum stent CSA by IVUS was 62 +/- 10% of the expected stent area. CONCLUSIONS: Despite moderately high-pressure inflations, the mean minimum stent CSA actually achieved was, on average, only 62% of the manufacturer's expected stent area. To optimize stent deployment, these IVUS observations should be considered during coronary artery stenting.

Anticoagulation in pregnancy and the puerperium.

For the management of acute thrombotic events in pregnancy therapeutic doses of low molecular weight heparins (LMWH) may be used, unless the shorter half-life of intravenous unfractionated heparin (UH) and predictable reversibility by protamine are important. Treatment should be continued up until delivery and into the puerperium. Pregnant women who have had an acute thrombotic event should be delivered by a specialist team. In the case of recent thrombosis, delivery should be planned and the time during which anticoagulation therapy is ceased around the time of delivery should be minimised. Therapeutic doses of LMWH contraindicate the use of regional anaesthesia, and a switch to intravenous UH before delivery may allow greater flexibility in this regard. Prophylactic doses of LMWH can be used to reduce the risk of recurrent thromboembolic events in pregnancy. The regimen used will depend on the previous history, the family history and the presence of risk factors, including the genetic and acquired causes of thrombophilia. Women with mechanical heart valves are at high risk during pregnancy and require therapeutic anticoagulation throughout pregnancy under the direction of experienced specialists. Low-dose aspirin can reduce the risk of recurrent pre-eclampsia by about 15%, but the role of UH and LMWH in the prevention of recurrent miscarriage or obstetric complications associated with uteroplacental insufficiency is still uncertain.

Blood pressure in late pregnancy and work outside the home.

OBJECTIVE: To assess maternal blood pressure (BP) responses to working outside the home in late pregnancy, using 24-hour ambulatory BP monitoring. METHODS: Our paired observational study involved 24-hour ambulatory BP monitoring of 100 normotensive women (51 primiparas, 49 multiparas) on work and nonwork days. Mean BP differences were calculated for working, postworking, sleeping, and 24-hour periods on both days. Main outcome measures were BP differences between work and nonwork days and subsequent pregnancy hypertension. Comparisons in BP between work and nonwork days were done with Student paired t test. Comparisons between study subgroups were done with unpaired t test. Potential predictors of change in BP were examined using multiple linear regression. RESULTS: During job time, BP was significantly higher on work days than on nonwork days. The mean increase in BP associated with work was 2.6 mmHg (systolic BP, P <.001), 2.8 mmHg (diastolic BP, P <.001), and 2.9 mmHg (mean arterial BP, P <.001). Those observations were independent of parity. More than 10% of our subjects had increased mean arterial BP of 10 mmHg or more during job time on work days compared with nonwork days. Higher absolute BP levels (regression coefficient 0.21, P =.04) and greater perceived job stress (regression coefficient 1.34, P =.04) correlated positively with BP increases at work. Twelve women developed hypertension. Those women had a larger increase on work days in mean systolic (6.6 mmHg compared with 2.1 mmHg, P =.013), mean diastolic (6.4 mmHg compared with 2.3 mmHg, P =.014), and mean arterial (7.4 mmHg compared with 2.3 mmHg, P =.002) BP compared with normotensive women. The magnitude of BP responses to work was a significant predictor of pregnancy hypertension, independent of absolute BP level. CONCLUSION: Blood pressure increased in women when they worked outside the home. The effect of maternal work is important when treating pregnancy hypertension. Ambulatory BP monitoring makes assessment of maternal BP responses to work a practical clinical option.

Blood-pressure measurement and classification in pregnancy.

Pre-eclampsia is usually defined on the basis of new onset hypertension and albuminuria developing after 20 weeks of pregnancy. There are difficulties with measurement of these variables. Conventional sphygmomanometry remains the gold standard for blood-pressure measurement. The value of ambulatory blood-pressure measurement has yet to be established. Oedema is now omitted from all definitions of preeclampsia, although the finding of widespread severe oedema of sudden onset should not be ignored for clinical purposes. Definitions of pre-eclampsia based solely on hypertension and proteinuria ignore the wide clinical variability in this syndrome. Women with no proteinuria but who do have hypertension and other features such as severe headache or other symptoms, thrombocytopenia, hyperuricaemia, disordered liver function, and fetal compromise are likely to have pre-eclampsia. This notion is accepted in the new Australasian definition of pre-eclampsia and more than hinted at in the new American College of Obstetricians and Gynecologists' definition. Definitions used for clinical purposes should be as safe as practical; they are likely to include a considerable number of false positives. Most research studies are weakened if patients without the disease are included. Therefore, a separate stringent research definition of pre-eclampsia we also suggest.

Prothrombin G20210A mutation: is it associated with pre-eclampsia?

OBJECTIVE: A strong independent association between the prothrombin G20210A gene mutation and pre-eclampsia has been reported in an Italian population. This result was not confirmed in a subsequent study in a Dutch population. The objective of this study was to further test the hypothesis that the prothrombin G20210A mutation is associated with pre-eclampsia/eclampsia. METHODS: Seventeen eclamptics and 67 pre-eclamptics were recruited from 34 multicase Australian/New Zealand families. An additional 105 unrelated pre-eclamptic/eclamptic women and 119 parous women were recruited as controls. RESULTS: The overall incidence for the prothrombin G20210A gene mutation in the pre-eclamptic group was 3.6% (95% CI 1.2-8.2%) which was not significantly different from the control group 2.5% (95% CI 0.5-7.2%) (p = 0.73, OR 1.44, 95% CI 0.34-6.17). CONCLUSION: This study provides little evidence of a significant relationship between the prothrombin G20210A gene mutation and pre-eclampsia. Based on our results, we do not recommend testing for the prothrombin G20210A mutation in the routine investigation of women with pre-eclampsia.

The relationship between increased folate catabolism and the increased requirement for folate in pregnancy.

OBJECTIVES: To estimate the rate of folate catabolism in pregnant and nonpregnant women and to derive the recommended dietary allowance for folate. DESIGN: Prospective, observational study. SETTING: Rotunda Hospital, Dublin. WOMEN: Twenty-four healthy gravid women were studied once during each trimester and postpartum. Twenty-five nonpregnant controls were assessed before and after folic acid supplementation. INTERVENTIONS: Women provided 24-hour urine collections while adhering to a strict dietary regimen containing no exogenous folate catabolites. MAIN OUTCOME MEASURES: Urinary levels of p-acetamidobenzoylglutamate and p-aminobenzoylglutamate were measured by high pressure liquid chromatography. RESULTS: The 24-hour excretion of folate catabolites, expressed as mean [95% CI] folate equivalents in microg) progressively increased during pregnancy. A peak was reached in the third trimester (349.1 microg [308.1 to 390.1]) where the rate was more than twice the rate in the nonpregnant control group (136.4 microg [112.4 to 160.4]) (P < 0.001). Based on our results the recommended dietary allowance for folate in nonpregnant women should be 250 microg and this should rise during pregnancy to 430 microg in the second trimester and 540 microg in the third trimester. CONCLUSIONS: The rate of folate catabolism progressively increases during pregnancy reaching a peak in the third trimester at the time of maximal fetal growth. The increased demand for folate during pregnancy appears to be due to the accelerated breakdown of the vitamin because of its participation in cellular biosynthesis. These results provide a quantitative basis for the current debate on the appropriate recommended dietary allowance for folate in both pregnant and nonpregnant women.

Management of essential thrombocythaemia during pregnancy.

Essential thrombocythaemia is a rare myeloproliferative disorder that often presents with haemorrhagic or thrombotic complications. It may be detected incidentally in an asymptomatic younger adult and there are only a few case reports of essential thrombocythaemia in pregnant women. The risks posed by essential thrombocythaemia during pregnancy and its optimal management are uncertain. To determine if there is increased incidence of obstetric complications seen in women who have essential thrombocythaemia, we collected a large case series from a number of tertiary obstetric units in Australia and New Zealand. There were 30 pregnancies in 12 women who had essential thrombocythaemia. There were 17 live births (57%), 7 stillbirths (23%), 5 miscarriages (17%) and 1 ectopic (3%). Five pregnancies were complicated by placental abruption. When the outcomes of those women who received treatment with aspirin or interferon were compared to those that did not receive any treatment, there was a trend towards a higher livebirth rate (79% v. 38%, p = 0.06). Seven women were treated with aspirin and 5 had successful outcomes with no fetal complications. Four women were treated with alpha-interferon which reduced their platelet counts and all had successful outcomes with no fetal complication. These findings suggest that there is a high incidence of miscarriage, stillbirth and abruption in women with essential thrombocythaemia. Their pregnancies should be carefully monitored. Treatment with low dose aspirin and/or the use of alpha-interferon may be associated with an improved pregnancy outcome.

Alternative forms of a novel aspartyl protease gene are differentially expressed in human gestational tissues.

The aim of this study was to identify genes involved in human placentation. To do this, differential gene expression was assessed in the decidua (placental bed) from pre-eclamptic and normotensive pregnancies using the polymerase chain reaction (PCR)-based subtractive technique of representational difference analysis. A novel aspartyl protease (cathepsin D-like) cDNA sequence was isolated by virtue of its over-expression in the pre-eclamptic decidual sample tested. It was designated DAP-1 (for Decidual Aspartyl Protease 1). Using DAP-1 primer sequences a second cDNA (DAP-2) was subsequently isolated from decidual RNA by reverse transcription (RT)-PCR and found to be identical to DAP-1 apart from 80 additional and consecutive base pairs in the N-terminal coding region. In DAP-2, a stop codon within the unique 80 bp sequence was predicted to terminate translation immediately before the consensus active site residues. While Southern blotting was used to show that there are two loci with homology to DAP-1 in the human genome, it is postulated that alternative pre-mRNA splicing of the 80 bp exon is involved in the regulated expression of active (DAP-1) and inactive (DAP-2) forms of this novel protease; a mechanism similar to that involved in the regulated expression of Caspase-2, a protease involved in apoptosis. In other systems the regulation of alternative splicing is indicated by tissue specificity and developmental stage specificity of the various spliced products. In this context it was demonstrated that whereas DAP-1 was the major transcript expressed in decidua, the pattern was reversed in the adjacent placental tissue. It is proposed that tissue and developmental stage-specific expression of the DAP protease are important for the normal development and function of the uteroplacental tissues and that dysregulation of the control of DAP gene splicing may play a role in abnormal placentation, like that seen in pre-eclampsia.