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BACKGROUND: Associations between tobacco smoking during pregnancy and offspring asthma have been observed, but the role of nicotine and familial factors remains unclear. OBJECTIVE: To estimate the association between tobacco use in pregnancy, both smoking and Swedish oral moist snuff, and asthma/wheeze in the offspring, how it varies by the child's age and explore the influence of measured and unmeasured familial confounding. METHODS: Register-based cohort study with sibling comparisons. The cohort included 788 508 children, born in Sweden 2005-2012 with information on maternal tobacco use in pregnancy, followed until December 2015. Asthma was based on a validated algorithm using asthma diagnoses from hospital visits and prescribed asthma drugs from nationwide registers, both as incident asthma/wheeze in age 0-8 years and current asthma at ages 2, 3, 4, 5 and 6 years. RESULTS: For smoking during pregnancy (SDP), we saw a pattern with higher hazard ratios for asthma/wheeze around ages 5 and 18 months. Snuff did not show the same pattern. For current asthma, we saw the strongest association at age 2 years (adjOR=1.22, 95% CI: 1.17-1.28), for snuff it was weaker (adjOR=1.06, 95% CI: 0.96-1.18). When using sibling controls the estimates for SDP were clearly attenuated, albeit with wide confidence intervals. CONCLUSION AND CLINICAL RELEVANCE: We saw an association between SDP and asthma at early age. The association with snuff was clearly weaker. The associations with SDP were attenuated when adjusting for measured and unmeasured familial factors shared by siblings. Based on those results, nicotine seems to have a limited role in the association between SDP and asthma; rather environmental tobacco smoke and other familial factors seems to explain observed associations.

Background: Previous studies have found associations between smoking during pregnancy (SDP) and childhood asthma/wheeze. Although nicotine has been suggested as a causal agent, the mechanism is unclear. In Sweden, oral moist snuff (snus) is a common form of tobacco, with high nicotine levels, but no combustion. Aim: To estimate the association between tobacco use in pregnancy, both smoking and snus, and asthma/wheeze in the child, to examine the role of nicotine. Methods: Our cohort included 897 975 children, born in Sweden 2005-2012. Information on SDP and snus use came from the Medical Birth Registry. We based the asthma/wheeze outcome on diagnoses and drugs from national health registers, as incident asthma at age 0-7 yrs and prevalent asthma at ages 2-6 yrs. Results: For the association of SDP and asthma/wheeze, we saw a pattern with higher hazard ratios around 5 and 18 months of age (Figure 1). Snus did not show the same pattern. Prevalent asthma, showed the strongest association with SDP at age 2 yrs (adjOR=1.22 95% CI: 1.17-1.28). The corresponding estimates for snus was adjOR=1.06 (95% CI: 0.96-1.18). Conclusion: We saw an association between SDP and asthma at early age, but the association with snus was much weaker. The results suggest that nicotine is not a causal agent in the SDP – asthma association.

Maternal smoking is one of the most important preventable risk factors in pregnancy. Whether it is nicotine or combustion products, or possibly both, that cause the adverse effects is not clear. The common substance in snuff and cigarette smoke is nicotine.The main objective was to study whether it is safe to use snuff in pregnancy, and if cessation of tobacco use influences the risk of adverse effects on the health of the newborn. Methods: Studies I-III were all based on data from the Swedish Medical Birth Register. Information on tobacco use three months before pregnancy and in early pregnancy was obtained from the register and categorized as nonuser, smoker 1-9 cigarettes/day, smoker≥10 cigarettes/day or snuff user. Most epidemiological studies on tobacco use are based on self-reported information. Snuff use in pregnancy has not been validated previously. In study IV, self-reported snuff use in a cohort of pregnant women was validated by the use of a biomarker of nicotine exposure, cotinine. Results: In study I, the association between smoking or snuff use in pregnancy and risk of neonatal apnea was investigated. Maternal snuff use was associated with an almost twofold risk of neonatal apnea. In contrast, the increased risk of apnea in smokers was not significant after adjustment for gestational age, indicating different mechanisms for nicotine and tobacco smoke. Study II investigated the association between tobacco use and risk of oral cleft malformations. Both maternal smoking and snuff use were associated with increased risk of oral cleft malformations. However, infants of women who had stopped smoking or using snuff before the antenatal booking were not at an increased risk of oral cleft malformations compared to that of nonusers. In study III, the association between maternal smoking, snuff use and preterm birth was studied. Maternal smoking was associated with extremely (<28 weeks), very (28-<32 weeks) and moderately (32-<37 weeks) preterm birth. Snuff use

Objective To study the associations of maternal tobacco use (smoking or use of snuff) and risk of extremely preterm birth, and if tobacco cessation before antenatal booking influences this risk. To study the association between tobacco use and spontaneous or medically indicated onset of delivery. Design Population-based cohort study. Setting Sweden. Population All live singleton births, registered in the Swedish Medical Birth Register, 1999-2012. Methods Odds ratios (OR) with 95% confidence intervals (CI) were calculated using multiple logistic regression analysis. Main outcome measures Extremely preterm birth (<28 weeks of gestation), very preterm birth (28-31 weeks), moderately preterm birth (32-36 weeks). Results Maternal snuff use (OR 1.58; 95% CI: 1.14-2.21) and smoking (OR 1.61; 95% CI: 1.39-1.87 and OR 1.91; 95% CI: 1.53-2.39 for moderate and heavy smoking, respectively) were associated with an increased risk of extremely preterm birth. When cessation of tobacco use was obtained there was no increased risk of preterm birth. Snuff use was associated with a twofold risk increase of medically indicated extremely preterm birth, whereas smoking was associated with increased risks of both medically indicated and spontaneous extremely preterm birth. Conclusions Snuff use and smoking in pregnancy were associated with increased risks of extremely preterm birth. Women who stopped using tobacco before the antenatal booking had no increased risk. These findings indicate that nicotine, the common substance in cigarettes and snuff, is involved in the mechanisms behind preterm birth. The use of nicotine should be minimized in pregnancy.

Objective: To determine if maternal use of snuff (containing high levels of nicotine, low levels of nitrosamines and no combustion products) is associated with an increased risk of oral cleft malformations in the infant and whether cessation of snuff use or smoking before the antenatal booking influences the risk. Method: A population-based cohort study was conducted on all live born infants, recorded in the Swedish Medical Birth Register from 1999 through 2009 (n = 1 086 213). Risks of oral clefts were evaluated by multivariate logistic regression analyses (using adjusted odds ratios, with 95% confidence intervals [CI]). Results: Among 975 866 infants that had information on maternal tobacco use, 1761 cases of oral clefts were diagnosed. More than 50% of the mothers who used snuff or smoked three months prior pregnancy stopped using before the antenatal booking. Almost 8% of the mothers were smoking at the antenatal booking and 1,1% of the mothers used snuff. Compared with infants of non-tobacco users, the adjusted odds ratios (95% CI) of any oral cleft for infants of mothers who continued to use snuff or to smoke were 1.48 [1.00-2.21] and 1.19 [1.01-1.41], respectively. In contrast, in infants of mothers who stopped using snuff or stopped smoking before the antenatal booking, the corresponding risks were not increased (adjusted odds ratios [95% CI] were 0.71 [0.44-1.14] and 0.88 [0.73-1.05], respectively). Conclusion: Maternal snuff use or smoking in early pregnancy is associated with an increased risk of oral clefts. Infants of mothers who stopped using snuff or stopped smoking before the antenatal booking had no increased risk of oral cleft malformations. Oral snuff or other sources of nicotine should not be recommended as an alternative for smoke-cessation during pregnancy.

Background: Maternal smoking is associated with disturbed cardiorespiratory control in the infant. Despite lacking knowledge of whether the harmful effects of smoking are caused by combustion products in tobacco smoke or by nicotine, it has been argued that nicotine-replacement therapy during pregnancy is safer than smoking. Objective: The goal of this study was to investigate if the disturbances in cardiorespiratory control associated with maternal smoking are also seen in infants prenatally exposed to snuff. We hypothesized that prenatal nicotine exposure (via moist snuff) causes disturbances in autonomic control and thereby increases the risk of apnea in the newborn. Methods: In a nationwide Swedish cohort study, we studied associations between maternal tobacco use during pregnancy and neonatal apnea. Of 609 551 live-born singleton infants, 7599 were born to snuff-using mothers, 41 391 and 16 928 were born to light (1-9 cigarettes per day) and heavy (≥10 cigarettes per day) smokers, respectively. Logistic regression was used to calculate odds ratios, using 95% confidence intervals. Results: Compared with infants of nontobacco users, infants with prenatal exposure to snuff were at an increased risk of apnea even after adjustment for differences in gestational age (odds ratio: 1.96 [95% confidence interval: [1.30-2.96]) Smoking was associated with increased risk of apnea before, but not after, adjusting for gestational age. Conclusions: Snuff use during pregnancy is associated with a higher risk of neonatal apnea than smoking. Maternal use of snuff or nicotine-replacement therapy cannot be regarded as an alternative to smoking during pregnancy.

Uppsatsens syfte är att identifiera marknadsstrategier som möjliggör och stärker tillväxt i små medicinteknikföretag. Uppsatsen är en kvalitativ undersökning baserad på fallstudier av fem företag. Fallstudierna är baserade på intervjuer. Teorierna behandlar betydelsefulla faktorer för företags tillväxt, samt för de problem som är viktiga att överbrygga. Centrala områden är partnerskap och nätverk, marknadsorientering och internationalisering. Våra slutsatser: Små tillväxtföretag inom medicinteknik använder ungefär samma marknadsstrategier för att kommersialisera sin innovation. Det vanliga tillvägagångssättet är att genom sitt kontaktnät identifiera Key Opinion Leaders och Early Adopters för att få dem att testa produkten och sedan förhoppningsvis sprida ett gott rykte i branschen. Mellan den unga och den mogna marknaden finns ett gap som kan vara svårt att komma över. För att gapet ska bli mindre, är det viktigt att vara marknadsorienterad och ha ett stort nätverk. Genom att samarbeta med en partner kan små företag snabbare få tillgång till en stor etablerad kundkrets och lanseras på många marknader. Små tillväxtföretag har svårt att få tag i riskkapital och har därför inte möjlighet att bygga upp en egen försäljningsorganisation. F&U är oerhört resurskrävande och därför finns oftast inte mycket pengar över till att lansera den färdiga produkten. Nätverk och partnerskap är således viktigt för att företagen ska kunna sälja sina produkter och växa.

Inköp tillmäts större betydelse i företagen och synen på byggandet börjar ändras. Byggföretagen vill alla sänka sina inköpskostnader, och ser stora möjligheter till kostnadssänkningar vid en minskning av antalet leverantörer. Som ett led i detta vill de genomföra vissa standardiseringsåtgärder, och har även börjat undersöka möjligheten att utveckla ett mer industrialiserat byggande. För tio år sedan var alla våra fallföretags Inköp decentraliserade. Vi har i vår studie kunnat konstatera att företagens synsätt har ändrats, och att företagen nu i högre eller lägre grad strävar efter en mer centraliserad inköpsorganisation. Vi har även kunnat fastslå att företagen tillmäter Inköp en viktig roll, vilket bland annat visat sig i det att Inköp numera representeras i ledningen hos majoriteten av företagen.Studien har också visat att företagen använder sig av liknande inköpsstrategier, och att de har kommit olika långt i implementeringen av dessa. Vi har inte kunnat påvisa någon direkt anledning till varför företagen ligger långt framme eller långt bak i respektive strategi.Vi har dock, genom intervjuerna, genom valda teorier och genom våra analyser, tyckt oss kunna fastlägga att avgörande för respektive strategis långsiktiga framgång, är i vilken grad inköpen samordnas.