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- Cnattingius, Sven, et al.
(author)
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Maternal Obesity and Risk of Preterm Delivery
- 2013
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In: Journal of the American Medical Association (JAMA). - : American Medical Association (AMA). - 0098-7484 .- 1538-3598. ; 309:22, s. 2362-2370
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Journal article (peer-reviewed)abstract
- Importance Preterm birth is a leading cause of infant mortality, morbidity, and long-term disability, and these risks increase with decreasing gestational age. Obesity increases the risk of preterm delivery, but the associations between overweight and obesity and subtypes of preterm delivery are not clear. Objective To study the associations between early pregnancy body mass index (BMI) and risk of preterm delivery by gestational age and by precursors of preterm delivery. Design, Setting, and Participants Population-based cohort study of women with live singleton births in Sweden from 1992 through 2010. Maternal and pregnancy characteristics were obtained from the nationwide Swedish Medical Birth Register. Main Outcomes and Measures Risks of preterm deliveries (extremely, 22-27 weeks; very, 28-31 weeks; and moderately, 32-36 weeks). These outcomes were further characterized as spontaneous (related to preterm contractions or preterm premature rupture of membranes) and medically indicated preterm delivery (cesarean delivery before onset of labor or induced onset of labor). Risk estimates were adjusted for maternal age, parity, smoking, education, height, mother's country of birth, and year of delivery. Results Among 1 599 551 deliveries with information on early pregnancy BMI, 3082 were extremely preterm, 6893 were very preterm, and 67 059 were moderately preterm. Risks of extremely, very, and moderately preterm deliveries increased with BMI and the overweight and obesity-related risks were highest for extremely preterm delivery. Among normal-weight women (BMI 18.5-<25), the rate of extremely preterm delivery was 0.17%. As compared with normal-weight women, rates (%) and adjusted odds ratios (ORs [95% CIs]) of extremely preterm delivery were as follows: BMI 25 to less than 30 (0.21%; OR, 1.26; 95% CI, 1.15-1.37), BMI 30 to less than 35 (0.27%; OR, 1.58; 95% CI, 1.39-1.79), BMI 35 to less than 40 (0.35%; OR, 2.01; 95% CI, 1.66-2.45), and BMI of 40 or greater (0.52%; OR, 2.99; 95% CI, 2.28-3.92). Risk of spontaneous extremely preterm delivery increased with BMI among obese women (BMI >= 30). Risks of medically indicated preterm deliveries increased with BMI among overweight and obese women. Conclusions and Relevance In Sweden, maternal overweight and obesity during pregnancy were associated with increased risks of preterm delivery, especially extremely preterm delivery. These associations should be assessed in other populations.
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- Lindgren, Isa
(author)
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Cardiovascular beta-adrenergic signaling : Maturation and programming effects of hypoxia in a chicken model
- 2010
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Doctoral thesis (other academic/artistic)abstract
- Despite the importance of β-adrenergic receptors (βARs) in cardiovascular disease, not much is known about how prenatal hypoxia effects βAR signaling in the postnatal animal. Thus, the aim of this thesis was to characterize the pre- and postnatal maturation of the cardiovascular βARs and the effects of chronic prenatal hypoxia on βAR signaling in the embryo and adult animal using the chicken as experimental model.βARs belong to the seven-transmembrane receptor family of G-protein coupled receptors and are crucial for cardiovascular development, growth and regulation. In the cardiovascular system there are two dominant subtypes, β1AR and β2AR, whose main ligands are the biogenic catecholamines epinephrine and norepinephrine. When stimulated, βARs primarily couple to the stimulatory G-protein (Gas) that stimulates adenylyl cyclase to convert ATP to cAMP. cAMP increases ino- and chronotropy of the heart and causes relaxation of blood vessels. β2ARs also have the ability to switch to inhibitory G-protein (Gi) signaling that decreases the cAMP production. To protect the cardiovascular system from overstimulation, the βARs desensitize and downregulate in the case of prolonged elevation of catecholamines. This blunts the cardiovascular response and the mechanisms behind desensitization/downregulation, including the β2AR switch to Gi signaling, are closely linked to cardiovascular disease and are of immense importance in medical therapeutics.Hypoxic stress releases catecholamines and thereby triggers βAR responses and desensitization/downregulation mechanisms. Hypoxia quite commonly occurs in utero and it is well known that prenatal insults, like malnutrition or hypoxia, are coupled to an increased risk of developing adult cardiovascular disease. This is referred to as developmental programming and constitutes an important and modern field of research.In this thesis, I show that; 1) the developmental trajectory for organ growth, especially the heart, is affected by hypoxia, 2) chronic prenatal hypoxia causes cardiac embryonic βAR sensitization, but causes desensitization postnatally suggesting that there is a hypoxia-induced “programming” effect on adult β-adrenoceptor function, 3) the adult βAR desensitization following prenatal hypoxia is linked to a decrease in β1AR/β2AR ratio, a decrease in cAMP following βAR stimulation with isoproterenol and an increase in Gas, 4) the chorioallantoic (CA) membrane arteries display hypoxic vasoconstriction, but lack 8-adrenergic reactivity and 5) hypotension of the chronically hypoxic chicken embryo is linked to a potent βAR relaxation of the CA vasculature and an increased AR sensitivity of the systemic arteries with no changes in heart rate.In conclusion, chronic prenatal hypoxia causes growth restriction, re-allocation and has programming effects on the βAR system in the adult. The latter indicates that the βAR system is an important factor in studying hypoxic developmental programming of adult cardiovascular disease.
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- Lindgren, Isa, et al.
(author)
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Hypotension in the chronically hypoxic chicken embryo is related to the β-adrenergic response of chorioallantoic and femoral arteries and not to bradycardia
- 2011
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In: American Journal of Physiology. Regulatory Integrative and Comparative Physiology. - : American Physiological Society. - 0363-6119 .- 1522-1490. ; 301:4, s. R1161-R1168
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Journal article (peer-reviewed)abstract
- Prolonged fetal hypoxia leads to growth restriction and can cause detrimental pre- and postnatal alterations. The embryonic chicken is a valuable model to study such effects of prenatal hypoxia, but little is known about long-term hypoxic effects on cardiovascular regulation in the chicken embryo. We investigated heart rate and blood pressure responses to chronic prenatal hypoxia in the chicken embryo (19 days) and hypothesized that it would exhibit hypotension due to bradycardia and βAR-mediated relaxation of the systemic (femoral) and/or the chorioallantoic (CA) arteries. We first measured heart rate (HR) and blood pressure (BP) in 19 day embryos incubated from day 0 in normoxia or hypoxia (14-15% O2). Secondly, we studied β-adrenoceptor (βAR)-mediated contraction, relaxation to the β-adrenoceptor (βAR) agonist isoproterenol and relaxation to forskolin in femoral and CA arteries using wire myography techniques. Chronic hypoxia caused a close to significant hypotension compared to the controls (Mean arterial pressure 3.19±0.18 vs. 2.59±0.13 kPa, normoxia vs. hypoxia respectively, P=0.056), but not bradycardia. All vessels relaxed in response to βAR stimulation with isoproterenol, but the CAM arteries completely lacked an βAR response. Furthermore, hypoxia increased the sensitivity of femoral (but not CA arteries) to isoproterenol. Hypoxia also increased the responsiveness of femoral arteries to the adenylate cyclase activator forskolin. In conclusion, hypotension in chronically hypoxic chicken embryos is more likely the consequence of elevated levels of circulating catecholamines acting on vascular beds with exclusive (CA arteries) or exacerbated (femoral arteries) βAR-mediated relaxation, rather than a consequence of bradycardia.
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- Nyman Iliadou, Anastasia, et al.
(author)
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Familial factors confound the associationbetween maternal smoking during pregnancyand young adult offspring overweight
- 2010
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In: International Journal of Epidemiology. - : Oxford University Press (OUP). - 0300-5771 .- 1464-3685. ; 39:5, s. 1193-1202
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Journal article (peer-reviewed)abstract
- Background Smoking during pregnancy has been shown to increase the risks of several adverse birth outcomes. Associations with overweight and/or obesity in the offspring have also been suggested. We aim to investigate whether familial factors confound the association between maternal smoking during pregnancy and overweight in early adulthood in young Swedish males born 1983–88. Methods In a population-based Swedish cohort comprising 124 203 singleton males born to Nordic mothers between 1983 and 1988, we examined the association between maternal smoking during pregnancy and the risk of overweight in the offspring at age ∼18 years. We also investigated the association within siblings, controlling for common genes and shared environment. Results In the cohort analyses, the risk of overweight was increased in sons of smoking mothers compared with sons of non-smokers: adjusted odds ratios 1.41, 95% confidence interval (CI) 1.34–1.49, and 1.56, 95% CI 1.46–1.66, for one to nine cigarettes per day, and >10 cigarettes per day, respectively. Stratifying for maternal smoking habits across two subsequent male pregnancies, there was an increased risk of overweight for the second son only if the mother was smoking in both male pregnancies. The effect of smoking during pregnancy on the offspring’s body mass index was not present when the association was evaluated within full and half sibling pairs. Conclusion The association between maternal smoking during pregnancy and offspring’s risk of overweight appears to be confounded by familial factors.
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- Perni, Uma C., et al.
(author)
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Interpregnancy Change in Smoking Habits and Risk of Preeclampsia : A Population-Based Study
- 2012
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In: American Journal of Hypertension. - : Oxford University Press (OUP). - 0895-7061 .- 1941-7225. ; 25:3, s. 372-378
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Journal article (peer-reviewed)abstract
- BACKGROUND Maternal smoking has been associated with decreased risk of preeclampsia; however, it is uncertain whether this association is causal. An argument for causality would be strengthened if changes in smoking status across consecutive pregnancies were related to the risk of preeclampsia.METHODS We used data from the National Swedish Birth Register to ascertain the associations between changes in smoking status during the first two successive pregnancies and risk of preeclampsia in the second pregnancy in 371,627 women between 1992 and 2006. Multivariable logistic regression models were used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI).RESULTS Compared to women who did not smoke in either pregnancy, the risk of preeclampsia was reduced in women who smoked in both pregnancies (adjusted OR = 0.54; 95% CI = 0.47, 0.63), in those who only smoked in second pregnancy (OR = 0.76; 95% CI = 0.58, 0.99) and, to a lesser extent, in women who smoked only in the first pregnancy (OR = 0.81; 95% CI = 0.70, 0.94). History of preeclampsia in the first pregnancy did not substantially modify these associations.CONCLUSION These data add support to a causal interpretation of the observed inverse association between smoking during pregnancy and risk of preeclampsia.
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