Abstract-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 (nϭ12) or intrauterine growth retardation (nϭ9), 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%, Pϭ0.0356). 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%, Pϭ0.0115). 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. Key Words: factor V Leiden polymorphism Ⅲ thermolabile methylenetetrahydrofolate reductase polymorphism Ⅲ pregnancy Ⅲ venous thrombosis Ⅲ recurrent fetal loss Ⅲ genetic risk factors

II-2

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Objective To compare the obstetric outcomes and socio‐demographic factors in electronic cigarette (EC) users with cigarette smokers and non‐smokers in pregnancy. Design Prospective observational cohort study. Setting A large urban maternity hospital delivering almost 8500 infants per year. Population Pregnant women attending for antenatal care. Methods Electronic cigarette users at time of booking history were prospectively identified. Maternal and neonatal outcomes were compared with those of pregnant smokers and non‐smokers. Multiple logistic regression analysis was performed to estimate the association between the explanatory variables and birthweight. Main outcomes measures Infant birthweight, gestation at delivery, incidence of low birthweight. Results A total of 218 women with exclusive EC use and 195 women with dual use of both cigarettes and EC, had a live birth during the study period. EC users were of higher socio‐economic status than smokers. Infants born to EC users had a mean birthweight of 3470 g (± 555 g), which was similar to that of non‐smokers (3471 ± 504 g, P = 0.97) and significantly greater than that of smokers (3166 ± 502 g, P < 0.001). The mean birth centile of EC users was similar to non‐smokers (51st centile versus 47th centile, P = 0.28) and significantly greater than that of smokers (27th centile, P < 0.001). Dual users had a mean birthweight and birth centile similar to that of smokers. Conclusion The birthweight of infants born to EC users is similar to that of non‐smokers, and significantly greater than cigarette smokers. Dual users of both cigarettes and EC have a birthweight similar to that of smokers. Tweetable extract Birthweight of infants born to electronic cigarette users appears to be similar to that of non‐smokers.

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Low molecular weight heparin (LMWH) is widely regarded as the anticoagulant treatment of choice for the prevention and treatment of venous thromboembolism during pregnancy. However, previous studies have demonstrated that the pharmacokinetic profiles of LMWH vary significantly with increasing gestation. Consequently, it remains unclear whether LMWH regimens recommended for use in nonpregnant individuals can be safely extrapolated to pregnant women. The aims of this study were to assess the safety and the efficacy of tinzaparin sodium (Innohep) administered only once daily during pregnancy. A systematic retrospective review identified a cohort of 37 high-risk pregnancies which had been managed using tinzaparin 175 IU/kg once daily. In 26 cases, the index pregnancy had been complicated by development of an acute venous thromboembolism (17 deep vein thrombosis and nine pulmonary embolism). For each individual, case notes were examined and data extracted using a predetermined questionnaire. No episodes of recurrent venous thromboembolism were identified amongst this cohort of pregnancies managed using once daily LMWH administration. However, two unusual thrombotic complications were observed, including a parietal infarct in one patient, and a postpartum cerebral venous thrombosis in another. Once daily tinzaparin was well tolerated, with no cases of heparin-induced thrombocytopaenia, symptomatic osteoporosis, or foetal malformations. Tinzaparin dose modification based upon peak anti-Xa levels occurred in 45% of the cases examined. The present study is the largest study to have examined the clinical efficacy of once daily LMWH for use in pregnant women at high risk of venous thromboembolism. Our data support the safety and efficacy of antenatal tinzaparin at a dose of 175 IU/kg. In order to determine whether this once daily regimen provides equivalent (or indeed greater) thromboprophylaxis to twice daily LMWH regimens during pregnancy will require highly powered direct comparative studies.

The aim of the study was to document the role of laboratory investigations for unexpected stillbirths at term. It was a retrospective casenote review of 75 unexpected stillbirths at term from 1995 to 1999, at the National Maternity Hospital, Dublin, Republic of Ireland. Investigations performed included blood tests, chromosomal analysis, autopsy and placental histology. Perinatal autopsy was the most informative investigation with positive findings in 49% of cases. There were positive placental findings in 37% of cases. Six of the 26 cases showed abnormal karyotyping. Of the blood tests performed, the Kleihauer-Betke test was most informative, revealing a feto-maternal haemorrhage in 8% of cases and anticardiolipin antibodies were positive in 4% of cases. FBC, TORCH and glycosylated Hb were negative in all 75 patients. Despite thorough investigations 32 of cases (43%) remained unexplained.

Background: Most European countries have seen a decrease in the prevalence of adolescent smoking. This decrease has, however, been patterned by gender. Girls' smoking rates have now overtaken boys' in many European countries. The two genders may not, however, share the same smoking beliefs and this could explain differences between the genders in smoking prevalence. We describe gender differences in smoking beliefs and investigate variations between countries, along with their gender context. Methods: In 2016, we conducted the SILNE R study (Smoking Inequalities Learning from Natural Experiments -Renew) in 55 schools located in seven European countries: . We surveyed 12,979 students aged 14-16 years (50% were girls). We classified smoking beliefs into four categories: positive individual, positive social, negative individual, and negative social beliefs. We expected girls to score higher on the last three of those categories and we hypothesized that countries with a more genderequal culture would have less gender difference in beliefs about smoking. Results: One out of two smoking beliefs differed significantly between genders. Negative social beliefs were more common in girls, while beliefs about the dating-related aspects of smoking were more common in boys. We identified Germany and Belgium as the only countries with no gender differences in any of the belief scales. No correlation was found, however, between these scales and the Gender Inequality Index. Conclusions: In some countries, gender-specific interventions might be implemented; however, two opposing strategies might be used, depending on whether such programs are aimed at boys or girls.