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  • 1.
    Akhter, Tansim
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Larsson, Marita
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Wikström, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Naessén, Tord
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Artery Wall Layer Dimensions during Normal Pregnancy: A longitudinal study using non-invasive high-frequency ultrasound2013In: American Journal of Physiology. Heart and Circulatory Physiology, ISSN 0363-6135, E-ISSN 1522-1539, Vol. 304, no 2, H229-H234 p.Article in journal (Refereed)
    Abstract [en]

    The vascular effects of normal pregnancy were investigated by estimating the intima and media thicknesses of the common carotid artery separately using 22MHz ultrasound (Collagenoson, Meudt, Germany) in 57 healthy women with normal pregnancies and pregnancy outcomes, in all three trimesters and at one year postpartum. A thick intima, thin media and high intima/media (I/M) ratio are signs of a less healthy artery wall. The mean artery wall layer dimensions remained fairly constant during pregnancy but the intima thickness and I/M thickness ratio appeared to improve (decrease) postpartum (p<0.001 for both). The cardiovascular risk parameters age, body mass index (BMI), and blood pressure in the first trimester were associated with higher I/M ratios, especially in the second trimester, whereas higher serum estradiol levels were significantly associated with a lower I/M ratio. Changes from the first to second trimesters in I/M ratio, taking into account differential changes in intima and media thickness, were significantly (p<0.05-0.001) associated with all risk parameters tested except age, which was associated with increased intima thickness (p=0.02). Associations with third trimester values and changes from first to third trimesters were similar but less apparent. Thus, fairly constant mean artery wall layer dimensions during pregnancy appeared to improve postpartum. However, higher age, BMI or blood pressure, and lower serum estradiol levels in the first trimester appeared to negatively affect the artery wall, strongly suggesting that pregnancy has negative vascular effects in some women. A less likely explanation involves possible adaptation to physiological changes during and after pregnancy.

  • 2.
    Akhter, Tansim
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Larsson, Marita
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Wikström, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Naessén, Tord
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Individual Artery Wall Layer Dimensions Indicate Increased Cardiovascular Risk in Previous Severe Preeclampsia: An investigation using non-invasive high-frequency ultrasound2013In: Hypertension, ISSN 0194-911X, E-ISSN 1524-4563Article in journal (Refereed)
    Abstract [en]

    Preeclampsia, especially severe preeclampsia, is associated with an increased risk of cardiovascular disease later in life. However, ultrasound assessments of the common carotid artery intima-media thickness (CCA-IMT) do not convincingly demonstrate this. The aim of this study was to assess whether the individual thickness of the CCA intima and media layers and calculation of intima/media (I/M) ratio indicate an increased cardiovascular risk in women with previous severe PE. The thicknesses of the CCA intima and media layers were obtained by non-invasive high-frequency ultrasound (22 MHz) (Collagenoson, Meudt, Germany) in 42 women with previous severe preeclampsia and 44 women with previous normal pregnancies. A thick intima, thin media and high I/M ratio are signs of a less healthy artery wall. Women with previous severe preeclampsia had a thicker mean CCA intima and a higher I/M ratio than women with previous normal pregnancies (both p < 0.0001). CCA-IMT did not differ significantly between the groups. In receiver operating characteristic (ROC) curve analysis, both intima thickness and I/M ratio clearly discriminated between women with and without previous severe preeclampsia [area under the curve (AUC) about 0.95], whereas CCA-IMT did not (AUC 0.52). Estimation of the individual CCA intima and media layers using high-frequency ultrasound and calculation of the I/M ratio clearly demonstrated the well known increased cardiovascular risk in women with previous severe preeclampsia, whereas CCA-IMT did not. This method appears preferable to measuring CCA-IMT for imaging arterial effects and the increased cardiovascular risk in women with a history of previous severe preeclampsia.

  • 3.
    Akhter, Tansim
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Larsson, Marita
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Wikström, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Naessén, Tord
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Thicknesses of individual layers of artery wall indicate increased cardiovascular risk in severe pre-eclampsia2014In: Ultrasound in Obstetrics and Gynecology, ISSN 0960-7692, E-ISSN 1469-0705, Vol. 43, no 6, 675-680 p.Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Pre-eclampsia, especially severe pre-eclampsia, is associated with an increased risk of cardiovascular disease later in life. However, ultrasound assessments of the common carotid artery intima-media thickness (CCA-IMT) do not convincingly demonstrate this. The aim of this study was to assess whether the individual thickness of the CCA intima and media layers and calculation of intima/media ratio (I/M) indicate an increased cardiovascular risk in women with previous severe pre-eclampsia.

    METHODS: The thicknesses of the CCA intima and media layers were obtained by non-invasive high-frequency ultrasound (22 MHz) in 42 women with previous severe pre-eclampsia and 44 women with previous normal pregnancies. A thick intima, thin media and high I/M are signs of a less healthy artery wall.

    RESULTS: Women with previous severe pre-eclampsia had a thicker CCA intima and a higher I/M than women with previous normal pregnancies, also after adjustment for mean arterial pressure, body mass index and CCA-IMT (all p < 0.0001). CCA-IMT did not differ significantly between the groups. In receiver operating characteristic curve analysis, intima thickness and I/M clearly discriminated between women with and without previous pre-eclampsia (c value about 0.95), whereas CCA-IMT did not (c = 0.52).

    CONCLUSIONS: Estimation of the individual CCA intima and media layers using high-frequency ultrasound and calculation of the I/M clearly demonstrated the well known increased cardiovascular risk in women with pre-eclampsia, whereas CCA-IMT did not. This method appears preferable to measuring CCA-IMT for imaging arterial effects and the increased cardiovascular risk in women with previous severe pre-eclampsia.

  • 4.
    Akhter, Tansim
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Wikström, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Naessen, Tord
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Changes in the Artery Wall Layer Dimensions in Women with Preeclampsia: an investigation using non-invasive high frequency ultrasound2012In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 91, no S159, 28-28 p.Article in journal (Other academic)
    Abstract [en]

    Background:

    Preeclampsia (PE) is associated with increased risk for cardiovascular disease later in life. Whether, the artery wall layer dimensions differ between PE and normal pregnancy is unclear. The aim of this study was to estimate if women with PE have different common carotid artery wall layer dimensions than women with normal pregnancy, both during pregnancy and about one year postpartum.

    Methods:

    By using high-frequency (22MHz) ultrasound (Collagenoson, Meudt, Germany) separate estimates of the common carotid artery intima and media layers were obtained and the I/M ratio was calculated in women with PE (n=55 during pregnancy and n=48 at postpartum) and with normal pregnancy (n=65 during pregnancy and n=59 at postpartum). Thick intima, thin media and a high intima/media ratio are signs of less healthy artery wall and vice versa.

    Results:

    In women with PE, the intima was thicker (0.18 } 0.03 vs. 0.11 } 0.02; p < .001), the media was thinner (0.47 } 0.12 vs. 0.55 } 0.14; p = .001) and the I/M ratio was higher (0.41 } 0.14 vs. 0.20 } 0.05; p < .001) compared to women with normal pregnancy. Further, for changes from pregnancy to postpartum, both for PE and normal pregnancy, the intima and the I/M ratio had improved but still significantly higher in women with PE than in women with normal pregnancy.

    Conclusion:

    In women with PE, we found a thicker intima, thinner media and a higher I/M ratio compared to women with normal pregnancy, indicating a more negatively affected artery wall layer dimensions. Persisting negative effects of PE on artery wall at postpartum, despite improvement of artery wall layers compared to values during pregnancy, indicates a permanent damage of the vascular system in this group of women.

  • 5.
    Akhter, Tansim
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Wikström, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Larsson, Marita
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Wikström, Gerhard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Naessén, Tord
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Association between angiogenic factors and signs of arterial aging in women with pre-eclampsia2017In: Ultrasound in Obstetrics and Gynecology, ISSN 0960-7692, E-ISSN 1469-0705, Vol. 50, 93-99 p.Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Pre-eclampsia (PE) is associated with an increased risk of cardiovascular disease (CVD) later in life. In PE there is a substantial increase in levels of the anti-angiogenic factor soluble fms-like tyrosine kinase-1 (sFlt1) and decreased levels of the pro-angiogenic factor placental growth factor (PlGF). Elevated levels of sFlt1 are also found in individuals with CVD. The aims of this study were to assess sFlt1, PlGF and the sFlt1/PlGF ratio and their correlation with signs of arterial aging by measuring common carotid artery (CCA) intima and media thicknesses and their ratio (I/M ratio) in women with and without PE.

    METHODS: Serum sFlt1 and PlGF levels were measured using commercially available enzyme-linked immunosorbent assay kits, and CCA intima and media thicknesses were estimated using high-frequency (22 MHz) ultrasonography in 55 women at PE diagnosis and 64 women with normal pregnancies at a similar gestational age, with reassessment one year postpartum. A thick intima, thin media and a high I/M ratio indicate a less healthy arterial wall.

    RESULTS: During pregnancy, higher levels of sFlt1, lower levels of PlGF and thicker intima, thinner media and higher I/M ratios were found in women with PE vs. controls (all p < 0.0001). Further, sFlt1 and the sFlt1/PlGF ratio were positively correlated with intima thickness and I/M ratio (all p < 0.0001), but negatively correlated with media thickness (p = 0.002 and 0.03, respectively). About one year postpartum, levels of sFlt1 and the sFlt1/PlGF ratio had decreased in both groups, but compared with controls women in the PE group still had higher levels (p = 0.001 and 0.02, respectively). Further, sFlt1 levels and the sFlt1/PlGF ratio were still positively correlated with intima thickness and I/M ratio.

    CONCLUSIONS: Higher sFlt1 levels and sFlt1/PlGF ratios in women with PE were positively associated with signs of arterial aging during pregnancy. About one year postpartum sFlt1 levels and the sFlt1/PlGF ratios were still higher in the PE group, and also associated with the degree of arterial aging.

  • 6.
    Akhter, Tansim
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Wikström, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology. Karolinska Inst, Danderyd Hosp, Dept Clin Sci, Stockholm, Sweden.
    Larsson, Marita
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Wikström, Gerhard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Naessén, Tord
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Serum Pentraxin 3 is associated with signs of arterial alteration in women with preeclampsia.2017In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 241, 417-422 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Preeclampsia (PE) in pregnancy is a state of exaggerated inflammation and is associated with an increased risk of cardiovascular disease (CVD) later in life. Levels of pentraxin 3 (PTX3), a novel inflammation marker, are increased during PE and in individuals with CVD. The primary aim of this study was to assess whether serum PTX3 in women with PE is associated with adverse arterial effects; a thicker intima and higher intima/media (I/M) ratio in the common carotid artery (CCA).

    METHODS: Serum PTX3 levels were measured using commercially available enzyme-linked immunosorbent assay kits, and individual CCA intima and media thicknesses were estimated by 22MHz non-invasive ultrasound in 55 women at PE diagnosis and 64 women with normal pregnancies at a similar gestational age, and about one year postpartum. A thick intima, thin media and high I/M ratio indicate a less healthy artery wall.

    RESULTS: During pregnancy serum PTX3 correlated positively with intima thickness and I/M ratio but negatively with media thickness (all p<0.0001), indicating adverse arterial effects. About one year postpartum, PTX3 levels had decreased in both groups and there remained no significant group difference or significant correlation with CCA wall layers.

    CONCLUSIONS: Higher levels of serum PTX3 in women with PE were significantly associated with signs of adverse arterial effects during pregnancy, but not one year postpartum, supporting the rapid dynamics of PTX3.

  • 7.
    Akhter, Tansim
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Wikström, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Larsson, Marita
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Naessén, Tord
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Individual Common Carotid Artery Wall Layer Dimensions, but Not Carotid Intima-Media Thickness, Indicate Increased Cardiovascular Risk in Women With Preeclampsia: An investigation using non-invasive high-frequency ultrasound2013In: Circulation Cardiovascular Imaging, ISSN 1941-9651, E-ISSN 1942-0080, Vol. 6, no 5, 762-768 p.Article in journal (Refereed)
    Abstract [en]

    Background Preeclampsia (PE) is associated with increased risk of cardiovascular disease later in life. Ultrasound assessment of the common carotid artery intima-media thickness (IMT) during or after PE has not indicated any increased cardiovascular risk. Methods and Results We used high-frequency ultrasound (22 MHz) to estimate the individual common carotid artery IMTs in 55 women at PE diagnosis and in 64 women with normal pregnancies at a similar stage. All were re-examined about 1 year postpartum. A thick intima, thin media, and high intima/media (I/M) ratio are signs of a less healthy artery wall. PE was associated with a significantly thicker mean common carotid artery intima, thinner media, and higher I/M ratio than in normal pregnancy (mean I/M difference, 0.21; 95% confidence interval, 0.17-0.25; P<0.0001). After adjustment for first trimester body mass index and mean arterial pressure, differences in intima thickness and I/M remained significant. About 1 year postpartum, these values had improved in both groups, but group differences remained significant (all adjusted P<0.0001). There were no significant differences in IMT between groups. In receiver-operating characteristic curve analysis, intima thickness and I/M were strongly predictive of prevalent PE (area under the curve, approximate to 0.95), whereas IMT was not (area under the curve, 0.49). Conclusions The arteries of women with PE were negatively affected during pregnancy and 1 year postpartum compared with women with normal pregnancies, indicating increased cardiovascular risk. Estimation of intima thickness and I/M ratio seem preferable to estimation of common carotid artery IMT in imaging cardiovascular risk in PE. Results from this pilot study warrant further confirmation.

  • 8.
    Altman, Maria
    et al.
    Dept of Medicine Solna, Clinical Epidemiological Unit, T2 Karolinska Institutet, Stockholm, Sweden.
    Edstedt Bonamy, Anna-Karin
    Dept of Medicine Solna, Clinical Epidemiological Unit, T2 Karolinska Institutet, Stockholm, Sweden.
    Wikström, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Cnattingius, Sven
    Dept of Medicine Solna, Clinical Epidemiological Unit, T2 Karolinska Institutet, Stockholm, Sweden.
    Cause-specific infant mortality in a population-based Swedish study of term and post-term births: the contribution of gestational age and birth weight2012In: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 2, no 4, e001152- p.Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE:

    To investigate infant mortality and causes of infant death in relation to gestational age (GA) and birth weight for GA in non-malformed term and post-term infants.

    DESIGN:

    Observational, retrospective nationwide cohort study.

    SETTING:

    Sweden 1983-2006.

    PARTICIPANTS:

    2 152 738 singleton non-malformed infants born at 37 gestational weeks or later.

    MAIN OUTCOME MEASURES:

    Infant, neonatal and postneonatal mortality and causes of infant death.

    RESULTS:

    Infant mortality rate was 0.12% (n=2687). Compared with infants born at 40 weeks, risk of infant mortality was increased among early term infants (37 weeks, adjusted OR 1.70, 95% CI 1.43 to 2.02). Compared with infants with normal birth weight for GA, very small for gestational age (SGA; <3rd percentile) infants faced a doubled risk of infant mortality (adjusted OR 2.13, 95% CI 1.80 to 2.53), and corresponding risk was also increased among moderately SGA infants (3rd to <10th percentile; adjusted OR 1.46, 95% CI 1.26 to 1.68). Sudden infant death syndrome (SIDS) was the most common cause of death, accounting for 39% of all infant mortality. Compared with birth at 40 weeks, birth at 37 weeks was associated with increased risks of death by infections, cardiovascular disorders, SIDS and malignant neoplasms. Very and moderately SGA were associated with increased risks of death by neonatal respiratory disorders, infections, cardiovascular disorders, SIDS and neuromuscular disorders. High birth weight for GA was associated with increased risks of death by asphyxia and malignant neoplasms.

    CONCLUSION:

    Early term birth and very to moderately low birth weight for GA are independent risk factors for infant mortality among non-malformed term infants.

  • 9.
    Baba, S
    et al.
    Department of Medicine, Clinical Epidemiology Unit, Karolinska Institutet, Stockholm, Sweden.
    Wikström, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Stephansson, O
    Department of Medicine, Clinical Epidemiology Unit, Karolinska Institutet, Stockholm, Sweden.
    Cnattingius, S
    Department of Medicine, Clinical Epidemiology Unit, Karolinska Institutet, Stockholm, Sweden.
    Changes in snuff and smoking habits in Swedish pregnant women and risk for small for gestational age births2013In: British Journal of Obstetrics and Gynecology, ISSN 1470-0328, E-ISSN 1471-0528, Vol. 120, no 4, 456-462 p.Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE:

    To examine associations between antenatal exposure to Swedish oral moist snuff (which includes essentially only nicotine) and to smoking and risks of small-for-gestational-age (SGA) births and to compare risks among women who stopped or continued using snuff or smoking during pregnancy.

    DESIGN:

    Population-based cohort study.

    SETTING:

    Sweden.

    POPULATION:

    All live singleton births in Sweden 1999-2010.

    METHODS:

    Odds ratios (OR) with 95% confidence intervals (CI) were calculated using multiple logistic regression analysis.

    MAIN OUTCOME MEASURES:

    SGA birth, also stratified into preterm (≤36 weeks of gestation) and term (≥37 weeks of gestation) SGA births.

    RESULTS:

    Compared with non-tobacco users in early pregnancy, snuff users and above all smokers in early pregnancy had increased risks of SGA births: adjusted ORs (95% CI) were 1.26 (1.09-1.46) and 2.55 (2.43-2.67), respectively). Snuff use had, if anything, a stronger association with preterm SGA than term SGA, whereas the opposite was true for smoking. Compared with non-tobacco users, women who stopped using snuff before their first visit to antenatal care had no increased risks of preterm or term SGA, and women who stopped using snuff later during pregnancy had no increased risk of term SGA. Smoking cessation early in pregnancy was associated with a larger reduction in risk than smoking cessation later in pregnancy.

    CONCLUSIONS:

    As both smoking and snuff use influence risk of SGA, both nicotine but above all tobacco combustion products are involved in the mechanisms by which maternal smoking increases the risk of SGA.

  • 10. Baba, Sachiko
    et al.
    Wikström, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Stephansson, Olof
    Cnattingius, Sven
    Influence of smoking and snuff cessation on risk of preterm birth2012In: European Journal of Epidemiology, ISSN 0393-2990, E-ISSN 1573-7284, Vol. 27, no 4, 297-304 p.Article in journal (Refereed)
    Abstract [en]

    The mechanisms by which antenatal smoking exposure increases the risk of preterm birth remain unknown. Swedish oral moist snuff contains quantities of nicotine comparable to those typically absorbed from cigarette smoking, but does not result in exposure to the products of combustion, for example carbon monoxide. In a nationwide study of 776,836 live singleton births in Sweden from 1999 to 2009, the authors used multiple logistic regression models to examine associations between cessation of smoking and Swedish snuff use early in pregnancy and risk of preterm birth (before 37 weeks). Compared with nontobacco users both before and in early pregnancy, the adjusted odds ratios (OR), 95 % confidence interval (CI) were OR = 0.92, 95 % CI 0.84-1.01, for women who stopped using snuff, and OR = 0.90, 95 % CI 0.87-0.94, for women who stopped smoking. In contrast, continued snuff use and smoking were associated with increased risks of preterm birth (adjusted OR = 1.29, 95 % CI 1.17-1.43, adjusted OR = 1.30, 95 % CI 1.25-1.36, respectively). The snuff and smoking-related risks were, if anything, higher for very (before 32 weeks) than moderately (32-36 weeks) preterm birth, and also higher for spontaneous than induced pretermbirth. These findings suggest that antenatal exposure to nicotine is involved in the mechanism by which tobacco use increase the risk of preterm birth.

  • 11. Baba, Sachiko
    et al.
    Wikström, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Stephansson, Olof
    Cnattingius, Sven
    Influence of Snuff and Smoking Habits in Early Pregnancy on Risks for Stillbirth and Early Neonatal Mortality2014In: Nicotine & tobacco research, ISSN 1462-2203, E-ISSN 1469-994X, Vol. 16, no 1, 78-83 p.Article in journal (Refereed)
    Abstract [en]

    Prenatal exposure to Swedish snuff (including nicotine and other components in grinded tobacco) is reported to increase stillbirth risk, but the effect of snuff on early neonatal mortality is unknown. Prenatal smoking exposure is associated with risks for both stillbirth and early neonatal mortality. We aimed to study if women who quit using snuff or quit smoking before first antenatal visit reduce their risks. In a nationwide study of 851,371 singleton births in Sweden from 1999 to 2010, we used multiple logistic regression models to examine associations between cessation or continuation of snuff use or smoking and risks for stillbirth (at 28 weeks or later) and early neonatal mortality (death during the first week of life). Compared with nontobacco users, snuff users and smokers in early pregnancy had increased risks for stillbirths, and adjusted odds ratios (ORs), with 95% confidence intervals (CI), were 1.43 (1.021.99) and 1.59 (1.401.80), respectively. Women who stopped using snuff or stopped smoking before first visit to antenatal care had no increased risks. Compared with nontobacco users, smokers had an increased risk for early neonatal mortality (adjusted OR 1.37 [95% CI 1.111.71]). Women who stopped smoking and snuff users in early pregnancy had no increased risks of early neonatal mortality. Both snuff and smoking influence risk for stillbirth, and women who stop using snuff or smoking have a similar stillbirth risk as nontobacco users. Smoking but not snuff use influences risk for early neonatal mortality.

  • 12.
    Belachew, Johanna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Cnattingius, S
    Clinical Epidemiology Unit, Department of Medicine, Karolinska Institute, Solna, Sweden.
    Mulic-Lutvica, Ajlana
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Eurenius, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Axelsson, Ove
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD). Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Wikström, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Risk of retained placenta in women previously delivered by caesarean section: a population-based cohort study.2014In: British Journal of Obstetrics and Gynecology, ISSN 1470-0328, E-ISSN 1471-0528, Vol. 121, no 2, 224-229 p.Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To evaluate whether women with a caesarean section at their first delivery have an increased risk of retained placenta at their second delivery.

    DESIGN: Population-based cohort study.

    SETTING: Sweden.

    POPULATION: All women with their first and second singleton deliveries in Sweden during the years 1994-2006 (n = 258 608). Women with caesarean section or placental abruption in their second pregnancy were not included in the study population.

    METHODS: The risk of retained placenta at second delivery was estimated for women with a first delivery by caesarean section (n = 19 458), using women with a first vaginal delivery as reference (n = 239 150). Risks were calculated as odds ratios by unconditional logistic regression analysis with 95% confidence intervals (95%) after adjustments for maternal, delivery, and infant characteristics.

    MAIN OUTCOME MEASURES: Retained placenta with normal (≤1000 ml) and heavy (>1000 ml) bleeding.

    RESULTS: The overall rate of retained placenta was 2.07%. In women with a previous caesarean section and in women with previous vaginal delivery, the corresponding rates were 3.44% and 1.96%, respectively. Compared with women with a previous vaginal delivery, women with a previous caesarean section had an increased risk of retained placenta (adjusted OR 1.45; 95% CI 1.32-1.59), and the association was more pronounced for retained placenta with heavy bleeding (adjusted OR 1.61; 95% CI 1.44-1.79).

    CONCLUSIONS: Our report shows an increased risk for retained placenta in women previously delivered by caesarean section, a finding that should be considered in discussions of mode of delivery.

  • 13.
    Bergman, Lina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Akhter, Tansim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Wikström, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Naessén, Tord
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Åkerud, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Plasma Levels of S100B in Preeclampsia and Association With Possible Central Nervous System Effects2014In: American Journal of Hypertension, ISSN 0895-7061, E-ISSN 1941-7225, Vol. 27, no 8, 1105-1111 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    S100B is supposed to be a peripheral biomarker of central nervous system (CNS) injury. The purpose of this study was to compare levels of S100B in women with preeclampsia with levels in healthy pregnant control subjects and furthermore to analyze levels of S100B in relation to possible CNS effects.

    METHODS:

    A cross-sectional case-control study in antenatal care centers in Uppsala, Sweden, was performed. Fifty-three women with preeclampsia and 58 healthy pregnant women were recruited at similar gestational length; women with preeclampsia were recruited at time of diagnosis, and control subjects were recruited during their routine visit to an antenatal clinic. Plasma samples were collected, and levels of S100B were analyzed with an enzyme-linked immunosorbent assay. Information about demographic and clinical characteristics, including symptoms related to CNS affection, was collected from the medical records. The main outcome measures were plasma levels of S100B and possible CNS effects.

    RESULTS:

    Levels of S100B were significantly higher among women with preeclampsia than among control subjects (0.12 µg/L vs. 0.07 µg/L; P < 0.001). In preeclampsia, there was a significant association between high levels of S100B and visual disturbances (P < 0.05).

    CONCLUSIONS:

    S100B is increased among women with preeclampsia, and high levels of S100B associate with visual disturbances, which might reflect CNS affection in women with preeclampsia.

  • 14.
    Bergman, Lina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Wikstrom, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Akhter, Tansim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Naessen, Tord
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Akerud, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Plasma Levels of S100B in Women with Preeclampsia2013In: Reproductive Sciences, ISSN 1933-7191, E-ISSN 1933-7205, Vol. 20, no S3, 115A-115A p.Article in journal (Other academic)
  • 15.
    Bergman, Lina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology. Clin Res Ctr, Dalarna, Sweden..
    Åkerud, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Wikström, Anna Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology. Danderyd Hosp, Karolinska Inst, Dept Clin Sci, Stockholm, Sweden..
    Larsson, Marita
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Naessén, Tord
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Akhter, Tansim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Cerebral Biomarkers in Women With Preeclampsia Are Still Elevated 1 Year Postpartum2016In: American Journal of Hypertension, ISSN 0895-7061, E-ISSN 1941-7225, Vol. 29, no 12, 1374-1379 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND There is evidence of cerebral involvement among women with preeclampsia. Levels of the cerebral biomarkers neuron-specific enolase (NSE) and S100B are elevated during pregnancy in women developing preeclampsia. It is although not known if these biomarkers return to normal range postpartum. The aim with this study was to compare levels of S100B and NSE during pregnancy and 1 year postpartum in women who have had preeclampsia to women with normal pregnancies. METHODS This study was a longitudinal study of cases (n = 53) with preeclampsia and controls (n = 58) consisted of normal pregnant women in matched gestational weeks. Plasma samples were collected at inclusion during pregnancy and 1 year postpartum. Plasma samples were analyzed for levels of S100B and NSE by enzyme-linked immunosorbent assays kits. RESULTS Levels of NSE and S100B in women with preeclampsia were higher during pregnancy than in women with normal pregnancies. One year postpartum, women who have had preeclampsia still had a higher median level of both NSE (5.07 vs. 4.28 mu g/l, P < 0.05) and S100B (0.07 vs. 0.06 mu g/l, P < 0.05) compared to women with previous normal pregnancies. High levels of NSE and S100B postpartum remained associated with previous preeclampsia after adjustment for confounding factors. Levels of NSE correlated to S100B during pregnancy and postpartum. CONCLUSIONS Levels of NSE and S100B are still elevated 1 year postpartum in women who have had preeclampsia in contrast to women with previous normal pregnancies. We hypothesize that there might be a persistent cerebral involvement among women with preeclampsia even 1 year postpartum.

  • 16.
    Bolin, Marie
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Wikström, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Wiberg-Itzel, Eva
    Department of Clinical Science and Education, Section of Obstetrics and Gynecology, Karolinska Institute, Södersjukhuset, Stockholm, Sweden.
    Olsson, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Ringvall, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Sundström-Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Axelsson, Ove
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i D län (CKFD).
    Thilaganathan, Basky
    Division of Clinical Development Sciences, Department of Obstetrics and Gynecology, St George’s University of London, England.
    Åkerud, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Prediction of Preeclampsia by Combining Serum Histidine-Rich Glycoprotein and Uterine Artery Doppler2012In: American Journal of Hypertension, ISSN 0895-7061, E-ISSN 1941-7225, Vol. 25, no 12, 1305-1310 p.Article in journal (Refereed)
    Abstract [en]

    Background

    Preeclampsia is associated with both maternal and perinatal morbidity and mortality. Histidine-rich glycoprotein (HRG) is a protein interacting with angiogenesis, coagulation, and inflammatory responses, processes known to be altered in preeclamptic pregnancies. Significantly lower levels of HRG have been demonstrated as early as in the first trimester in women later developing preeclampsia compared with normal pregnancies. The aim of this study was to investigate whether the combination of HRG and uterine artery Doppler ultrasonography can be used as a predictor of preeclampsia.

    Methods

    A total of 175 women were randomly selected from a case-control study; 86 women had an uncomplicated pregnancy and 89 women later developed preeclampsia. Blood samples and pulsatility index (PI) were obtained from both cases and controls in gestational week 14.

    Results

    HRG levels were significantly lower in women who developed preterm preeclampsia compared with controls, but not for women developing preeclampsia in general. PI was significantly higher in the preeclampsia group compared with controls, especially in preterm preeclampsia. The combination of HRG and PI revealed a sensitivity of 91% and a specificity of 62% for preterm preeclampsia.

    Conclusions

    The combination of HRG and uterine artery Doppler may predict preterm preeclampsia in early pregnancy.

  • 17.
    Bolin, Marie
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Åkerud, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Cnattingius, Sven
    Stephansson, Olof
    Wikström, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Hyperemesis gravidarum and risks of placental dysfunction disorders: a population-based cohort study2013In: British Journal of Obstetrics and Gynecology, ISSN 1470-0328, E-ISSN 1471-0528, Vol. 120, no 5, 541-547 p.Article in journal (Refereed)
    Abstract [en]

    Objective To study whether pregnancies complicated by hyperemesis gravidarum in the first (<12weeks) or second (1221weeks) trimester are associated with placental dysfunction disorders. Design Population-based cohort study. Setting Sweden. Population All pregnancies in the Swedish Medical Birth Register estimated to have started on 1 January 1997 or later and ended in a single birth on 31 December 2009 or earlier (n=1156050). Methods Odds ratios with 95% confidence intervals were estimated for placental dysfunction disorders in women with an inpatient diagnosis of hyperemesis gravidarum, using women without inpatient diagnosis of hyperemesis gravidarum as reference. Risks were adjusted for maternal age, parity, body mass index, height, smoking, cohabitation with the infant's father, infant's sex, mother's country of birth, education, presence of hyperthyreosis, pregestational diabetes mellitus, chronic hypertension and year of infant birth. Main outcome measures Placental dysfunction disorders, i.e. pre-eclampsia, placental abruption, stillbirth and small for gestational age (SGA). Results Women with hyperemesis gravidarum in the first trimester had only a slightly increased risk of pre-eclampsia. Women with hyperemesis gravidarum with first admission in the second trimester had a more than doubled risk of preterm (<37weeks) pre-eclampsia, a threefold increased risk of placental abruption and a 39% increased risk of an SGA birth (adjusted odds ratios [95% confidence intervals] were: 2.09 [1.383.16], 3.07 [1.885.00] and 1.39 [1.061.83], respectively). Conclusions There is an association between hyperemesis gravidarum and placental dysfunction disorders, which is especially strong for women with hyperemesis gravidarum in the second trimester.

  • 18. Cnattingius, S.
    et al.
    Villamor, E.
    Lagerros, Y. T.
    Wikström, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Granath, F.
    High birth weight and obesity: a vicious circle across generations2012In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 36, no 10, 1320-1324 p.Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Rates of high birth weight infants, overweight and obese children and adults are increasing. The associations between birth weight and adult weight may have consequences for the obesity epidemic across generations. We examined the association between mothers' birth weight for gestational age and adult body mass index (BMI) and these factors' joint effect on risk of having a large-for-gestational-age (LGA) offspring (>+2 s.d. above the mean). DESIGN: A cohort of 162 676 mothers and their first-born offspring with birth information recorded on mothers and offspring in the nation-wide Swedish Medical Birth Register 1973-2006. RESULTS: Compared with mothers with appropriate birth weight for gestational age (AGA; -1 to +1 s.d.), mothers born LGA had increased risks of overweight (BMI 25.0-29.9; odds ratio (OR), 1.50; 95% CI 1.39-1.61), obesity class I (BMI 30.0-34.9; OR 1.77; 95% CI 1.59-1.98), obesity class II (BMI 35.0-39.9; OR 2.77; 95% CI 2.37-3.24) and obesity class III (BMI >= 40.0; OR 2.04; 95% CI 1.49-2.80). In each stratum of mother's birth weight for gestational age, risk of having an LGA offspring increased with mother's BMI. The risk of an LGA offspring was highest among women with a high (>= 30) BMI who also had a high birth weight for gestational age (>+1 s.d.). In these groups, the ORs for LGA offspring ranged from 5 to 14 when compared with mothers born AGA with normal BMI (<= 24.9). However, the strongest increase in risk by BMI was seen among mothers born SGA: the OR of having an LGA offspring was 13 times as high among SGA mothers with BMI >= 35.0 compared with the OR among SGA mothers with normal BMI (ORs = 4.61 and 0.35, respectively). CONCLUSIONS: Prenatal conditions are important for the obesity epidemic. Prevention of LGA births may contribute to curtail the intergenerational vicious cycle of obesity.

  • 19. Cnattingius, Sven
    et al.
    Villamor, Eduardo
    Johansson, Stefan
    Bonamy, Anna-Karin Edstedt
    Persson, Martina
    Wikström, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Granath, Fredrik
    Maternal Obesity and Risk of Preterm Delivery2013In: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 309, no 22, 2362-2370 p.Article in journal (Refereed)
    Abstract [en]

    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.

  • 20. Cnattingius, Sven
    et al.
    Villamor, Eduardo
    Johansson, Stefan
    Bonamy, Anna-Karin Edstedt
    Persson, Martina
    Wikström, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Granath, Fredrik
    Maternal Obesity and Risk of Preterm Delivery EDITORIAL COMMENT2013In: Obstetrical and Gynecological Survey, ISSN 0029-7828, E-ISSN 1533-9866, Vol. 68, no 11, 731-732 p.Article in journal (Other academic)
  • 21.
    Dahlin, S.
    et al.
    Karolinska Inst, Dept Med Solna, Clin Epidemiol Unit, Stockholm, Sweden..
    Gunnerbeck, A.
    Karolinska Inst, Dept Womens & Childrens Hlth, Neonatal Res Unit, Stockholm, Sweden.;Karolinska Univ Hosp, Astrid Lindgrens Children Hosp, Stockholm, Sweden..
    Wikström, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology. Karolinska Inst, Dept Med Solna, Clin Epidemiol Unit, Stockholm, Sweden..
    Cnattingius, S.
    Karolinska Inst, Dept Med Solna, Clin Epidemiol Unit, Stockholm, Sweden..
    Bonamy, A-K Edstedt
    Karolinska Inst, Dept Med Solna, Clin Epidemiol Unit, Stockholm, Sweden.;Karolinska Inst, Dept Womens & Childrens Hlth, Neonatal Res Unit, Stockholm, Sweden.;Soder Sjukhuset, Sachs Children & Youth Hosp, Stockholm, Sweden..
    Maternal tobacco use and extremely premature birth - a population-based cohort study2016In: British Journal of Obstetrics and Gynecology, ISSN 1470-0328, E-ISSN 1471-0528, Vol. 123, no 12, 1938-1946 p.Article in journal (Refereed)
    Abstract [en]

    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.

  • 22.
    DeRoo, Lisa
    et al.
    Univ Bergen, Dept Global Publ Hlth & Primary Hlth Care, Postboks 7804, N-5018 Bergen, Norway..
    Skjaerven, Rolv
    Univ Bergen, Dept Global Publ Hlth & Primary Hlth Care, Postboks 7804, N-5018 Bergen, Norway.;Norwegian Inst Publ Hlth, Med Birth Registry Norway, Bergen, Norway..
    Wilcox, Allen
    NIEHS, NIH, POB 12233, Res Triangle Pk, NC 27709 USA..
    Klungsoyr, Kari
    Univ Bergen, Dept Global Publ Hlth & Primary Hlth Care, Postboks 7804, N-5018 Bergen, Norway.;Norwegian Inst Publ Hlth, Med Birth Registry Norway, Bergen, Norway..
    Wikström, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology. Karolinska Univ Hosp, Dept Med, Clin Epidemiol Unit, Stockholm, Sweden.;Karolinska Inst, Stockholm, Sweden..
    Morken, Nils-Halvdan
    Univ Bergen, Dept Global Publ Hlth & Primary Hlth Care, Postboks 7804, N-5018 Bergen, Norway.;Univ Bergen, Dept Clin Sci, Bergen, Norway..
    Cnattingius, Sven
    Karolinska Univ Hosp, Dept Med, Clin Epidemiol Unit, Stockholm, Sweden.;Karolinska Inst, Stockholm, Sweden..
    Placental abruption and long-term maternal cardiovascular disease mortality: a population-based registry study in Norway and Sweden2016In: European Journal of Epidemiology, ISSN 0393-2990, E-ISSN 1573-7284, Vol. 31, no 5, 501-511 p.Article in journal (Refereed)
    Abstract [en]

    Women with preeclamptic pregnancies have increased long-term cardiovascular disease (CVD) mortality. We explored this mortality risk among women with placental abruption, another placental pathology. We used linked Medical Birth Registry and Death Registry data to study CVD mortality among over two million women with a first singleton birth between 1967 and 2002 in Norway and 1973 and 2003 in Sweden. Women were followed through 2009 and 2010, respectively, to ascertain subsequent pregnancies and mortality. Cox regression analysis was used to estimate associations between placental abruption and cardiovascular mortality adjusting for maternal age, education, year of the pregnancy and country. There were 49,944 deaths after an average follow-up of 23 years, of which 5453 were due to CVD. Women with placental abruption in first pregnancy (n = 10,981) had an increased risk of CVD death (hazard ratio 1.8; 95 % confidence interval 1.3, 2.4). Results were essentially unchanged by excluding women with pregestational hypertension, preeclampsia or diabetes. Women with placental abruption in any pregnancy (n = 23,529) also had a 1.8-fold increased risk of CVD mortality (95 % confidence interval 1.5, 2.2) compared with women who never experienced the condition. Our findings provide evidence that placental abruption, like other placental complications of pregnancy, is associated with women's increased risk of later CVD mortality.

  • 23.
    Eckerdal, Patricia
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Kollia, Natasa
    Department of Biostatistics, Harokopio University, Athens, Greece.
    Löfblad, Johanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Hellgren, Charlotte
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Karlsson, Linnea
    Department of Child Psychiatry, Turku University Hospital, Turku, Finland .
    Högberg, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Wikström, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Skalkidou, Alkistis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Delineating the Association between Heavy Postpartum Haemorrhage and Postpartum Depression2016In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 1, e0144274Article in journal (Refereed)
    Abstract [en]

    Objectives

    To explore the association between postpartum haemorrhage (PPH) and postpartum depression (PPD), taking into account the role of postpartum anaemia, delivery experience and psychiatric history.

    Methods

    A nested cohort study (n = 446), based on two population-based cohorts in Uppsala, Sweden. Exposed individuals were defined as having a bleeding of ≥1000ml (n = 196) at delivery, and non-exposed individuals as having bleeding of <650ml (n = 250). Logistic regression models with PPD symptoms (Edinburgh Postnatal Depression scale (EPDS) score ≥ 12) as the outcome variable and PPH, anaemia, experience of delivery, mood during pregnancy and other confounders as exposure variables were undertaken. Path analysis using Structural Equation Modeling was also conducted.

    Results

    There was no association between PPH and PPD symptoms. A positive association was shown between anaemia at discharge from the maternity ward and the development of PPD symptoms, even after controlling for plausible confounders (OR = 2.29, 95%CI = 1.15–4.58). Path analysis revealed significant roles for anaemia at discharge, negative self-reported delivery experience, depressed mood during pregnancy and postpartum stressors in increasing the risk for PPD.

    Conclusion

    This study proposes important roles for postpartum anaemia, negative experience of delivery and mood during pregnancy in explaining the development of depressive symptoms after PPH.

  • 24.
    Elden, Helen
    et al.
    Gothenburg Univ, Sahlgrenska Acad, Inst Hlth & Caring Sci, S-40530 Gothenburg, Sweden..
    Hagberg, Henrik
    Gothenburg Univ, Sahlgrenska Univ Hosp, Sahlgrenska Acad, Perinatal Ctr,Dept Obstet & Gynecol,Inst Clin Sci, S-41685 Gothenburg, Sweden..
    Wessberg, Anna
    Gothenburg Univ, Sahlgrenska Acad, Inst Hlth & Caring Sci, S-40530 Gothenburg, Sweden..
    Sengpiel, Verena
    Gothenburg Univ, Sahlgrenska Univ Hosp, Sahlgrenska Acad, Perinatal Ctr,Dept Obstet & Gynecol,Inst Clin Sci, S-41685 Gothenburg, Sweden..
    Herbst, Andreas
    Skane Univ Hosp, S-21428 Malmo, Sweden..
    Bullarbo, Maria
    Gothenburg Univ, Sahlgrenska Univ Hosp, Sahlgrenska Acad, Perinatal Ctr,Dept Obstet & Gynecol,Inst Clin Sci, S-41685 Gothenburg, Sweden..
    Bergh, Christina
    Gothenburg Univ, Sahlgrenska Univ Hosp, Sahlgrenska Acad, Dept Obstet & Gynecol,Inst Clin Sci,Reprod Med, S-41685 Gothenburg, Sweden..
    Bolin, Kristian
    Gothenburg Univ, Sch Business Econ & Law, Dept Econ & Stat, POB 640, S-40530 Gothenburg, Sweden..
    Malbasic, Snezana
    South Alvsborg Cty Hosp, Dept Obstet & Gynecol, S-50182 Boras, Sweden..
    Saltvedt, Sissel
    Karolinska Univ Hosp, Dept Obstet & Gynecol, S-17176 Stockholm, Sweden..
    Stephansson, Olof
    Karolinska Inst, Dept Med, Clin Epidemiol Unit, S-17176 Stockholm, Sweden.;Karolinska Univ Hosp, Dept Womens & Childrens Hlth, Div Obstet & Gynecol, S-17176 Stockholm, Sweden..
    Wikström, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Ladfors, Lars
    Gothenburg Univ, Sahlgrenska Univ Hosp, Sahlgrenska Acad, Perinatal Ctr,Dept Obstet & Gynecol,Inst Clin Sci, S-41685 Gothenburg, Sweden..
    Wennerholm, Ulla-Britt
    Gothenburg Univ, Sahlgrenska Univ Hosp, Sahlgrenska Acad, Perinatal Ctr,Dept Obstet & Gynecol,Inst Clin Sci, S-41685 Gothenburg, Sweden.;Karolinska Univ Hosp, Dept Obstet & Gynecol, S-17176 Stockholm, Sweden..
    Study protocol of SWEPIS a Swedish multicentre register based randomised controlled trial to compare induction of labour at 41 completed gestational weeks versus expectant management and induction at 42 completed gestational weeks2016In: BMC Pregnancy and Childbirth, ISSN 1471-2393, E-ISSN 1471-2393, Vol. 16, 49Article in journal (Refereed)
    Abstract [en]

    Background: Observational data shows that postterm pregnancy (>= 42 gestational weeks, GW) and late term pregnancy (>= 41 GW), as compared to term pregnancy, is associated with an increased risk for adverse outcome for the mother and infant. Standard care in many countries is induction of labour at 42 GW. There is insufficient scientific support that induction of labour at 41 GW, as compared with expectant management and induction at 42 GW will reduce perinatal mortality and morbidity without an increase in operative deliveries, negative delivery experiences or higher costs. Large randomised studies are needed since important outcomes; such as perinatal mortality and hypoxic ischaemic encephalopathy are rare events. Methods/Design: A total of 10 038 healthy women >= 18 years old with a normal live singleton pregnancy in cephalic presentation at 41 GW estimated with a first or second trimester ultrasound, who is able to understand oral and written information will be randomised to labour induction at 41 GW (early induction) or expectant management and induction at 42 GW (late induction). Women will be recruited at university clinics and county hospitals in Sweden comprising more than 65 000 deliveries per year. Primary outcome will be a composite of stillbirth, neonatal mortality and severe neonatal morbidity. Secondary outcomes will be other adverse neonatal and maternal outcomes, mode of delivery, women's experience, cost effectiveness and infant morbidity up to 3 months of age. Data on background variables, obstetric and neonatal outcomes will be obtained from the Swedish Pregnancy Register and the Swedish Neonatal Quality Register. Data on women's experiences will be collected by questionnaires after randomisation and 3 months after delivery. Primary analysis will be intention to treat. The statistician will be blinded to group and intervention. Discussion: It is important to investigate if an intervention at 41 GW is superior to standard care in order to reduce death and lifelong disability for the children. The pregnant population, >41 GW, constitutes 15-20 % of all pregnancies and the results of the study will thus have a great impact. The use of registries for randomisation and collection of outcome data represents a unique and new study design.

  • 25. Endler, M.
    et al.
    Saltvedt, S.
    Cnattingius, S.
    Stephansson, O.
    Wikström, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Retained placenta is associated with pre-eclampsia, stillbirth, giving birth to a small-for-gestational-age infant, and spontaneous preterm birth: a national register-based study2014In: British Journal of Obstetrics and Gynecology, ISSN 1470-0328, E-ISSN 1471-0528, Vol. 121, no 12, 1462-1470 p.Article in journal (Refereed)
    Abstract [en]

    ObjectiveTo evaluate whether defective placentation disorders, i.e. pre-eclampsia, stillbirth, small for gestational age (SGA), and spontaneous preterm birth, are associated with risk of retained placenta. DesignPopulation-based cohort study. SettingSweden. PopulationPrimiparous women in Sweden with singleton vaginal deliveries between 1997 and 2009 at 32-41weeks of gestation (n=386607), without placental abruption or infants with congenital malformations. MethodsRisks were calculated as odds ratios (ORs) by unconditional logistic regression with 95% confidence intervals (95%CIs) after adjustments for maternal, delivery, and infant characteristics. Main outcome measureRetained placenta, defined by the presence of both a diagnostic code (of retained placenta) and a procedure code (for the manual removal of the placenta). ResultsThe overall rate of retained placenta was 2.17%. The risk of retained placenta was increased for women with pre-eclampsia (adjusted OR, aOR, 1.37, 95%CI 1.21-1.54), stillbirth (aOR1.71, 95%CI 1.28-2.29), SGA birth (aOR1.47, 95%CI 1.28-1.70), and spontaneous preterm birth (32-34weeks of gestation, aOR2.35, 95%CI 1.97-2.81; 35-36weeks of gestation, aOR1.55, 95%CI 1.37-1.75). The risk was further increased for women with preterm pre-eclampsia (aOR1.69, 95%CI 1.25-2.28) and preterm SGA birth (aOR2.19, 95%CI 1.42-3.38). There was no association between preterm stillbirth (aOR1.10, 95%CI 0.63-1.92) and retained placenta, but the exposed group comprised only 15 cases. ConclusionsDefective placentation disorders are associated with an increased risk of retained placenta. Whether these relationships indicate a common pathophysiology remains to be investigated.

  • 26.
    Granfors, Michaela
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Andersson, Maria
    Human Nutrition Laboratory, Department of Health Sciences and Technology, Swiss Federal Institute of Technology (ETH) Zurich, Switzerland.
    Stinca, Sara
    Human Nutrition Laboratory, Department of Health Sciences and Technology, Swiss Federal Institute of Technology (ETH) Zurich, Switzerland.
    Åkerud, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Skalkidou, Alkistis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Sundström Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Wikström, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Filipsson Nyström, Helena
    Department of Endocrinology, Sahlgrenska University Hospital, Göteborg, Sweden.
    Iodine deficiency in a study population of pregnant women in Sweden2015In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 94, no 11, 1168-1174 p.Article in journal (Refereed)
    Abstract [en]

    Introduction

    Iodine deficiency in utero may impair neurological development of the fetus. In Sweden, iodine nutrition is considered to be adequate in the general population. The aim of this study was to evaluate iodine nutrition during pregnancy in Sweden.

    Material and methods

    In this cross-sectional study, the total study population (= 459) consisted of two cohorts (Värmland County, = 273, and Uppsala County, = 186) of pregnant non-smoking women without pre-gestational diabetes mellitus or known thyroid disease before or during pregnancy. Spot urine samples were collected in the third trimester of pregnancy for median urinary iodine concentration (UIC) analysis.

    Results

    The median UIC in the total study population was 98 μg/L (interquartile range 57–148 μg/L).

    Conclusions

    According to WHO/UNICEF/IGN criteria, population-based median UIC during pregnancy should be 150–249 μg/L. Thus, our results indicate insufficient iodine status in the pregnant population of Sweden. There is an urgent need for further assessments in order to optimize iodine nutrition during pregnancy.

  • 27.
    Granfors, Michaela
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Karypidis, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Hosseini, Frida
    Department of Clinical Sciences, Division of Obstetrics and Gynaecology, Karolinska Institutet and Danderyd Hospital, Stockholm, Sweden.
    Skjöldebrand-Sparre, Lottie
    Department of Clinical Sciences, Division of Obstetrics and Gynaecology, Karolinska Institutet and Danderyd Hospital, Stockholm, Sweden.
    Stavreus-Evers, Anneli
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Bremme, Katarina
    Department of Women´s and Children´s Health, Karolinska Institutet, Stockholm, Sweden.
    Landgren, Britth-Marie
    Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Sundström-Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Wikström, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Akerud, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Phosphodiesterase 8B gene polymorphism in women with recurrent miscarriage: A retrospective case control study.2012In: BMC Medical Genetics, ISSN 1471-2350, E-ISSN 1471-2350, Vol. 13, 121- p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Recurrent miscarriage affects approximately 1% of all couples. There is a known relation between hypothyroidism and recurrent miscarriage. Phosphodiesterase 8B (PDE8B) is a regulator of cyclic adenosine monophosphate (cAMP) with important influence on human thyroid metabolism. Single nucleotide polymorphism (SNP) rs 4704397 in the PDE8B gene has been shown to be associated with variations in serum Thyroid Stimulating Hormone (TSH) and thyroxine (T4) levels. The aim of this study was to investigate whether there is an association between the SNP rs 4704397 in the PDE8B gene and recurrent miscarriage. METHODS: The study was designed as a retrospective case control study. 188 cases with recurrent miscarriage were included and compared with 391 controls who had delivered at least once and with no history of miscarriage or assisted reproduction. RESULTS: No difference between cases and controls concerning age was found. Bivariate associations between homozygous A/A (OR 1.57, 95% CI 0.98-2.52) as well as G/G carriers (OR 1.52, 95% CI 1.02-2.25) of SNP rs 4704397 in PDE8B and recurrent miscarriage were verified (test for trend across all 3 genotypes, p = 0.059). After adjustment for known confounders such as age, BMI and smoking the association between homozygous A/A (AOR 1.63, 95% CI 1.01 - 2.64, p = 0.045) and G/G (AOR 1.52, 95% CI 1.02 - 2.27, p = 0.039) carriers of SNP rs 4704397 in PDE8B and recurrent miscarriage remained. CONCLUSIONS: Our findings suggest that there is an association between homozygous A/A as well as homozygous G/G carriers of SNP rs 4704397 in PDE8B and recurrent miscarriage.

  • 28.
    Granfors, Michaela
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Åkerud, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Berglund, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH). Uppsala University, National Centre for Knowledge on Men.
    Skogo, Johan
    Uppsala University, National Centre for Knowledge on Men.
    Sundström Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Wikström, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Thyroid Testing and Management of Hypothyroidism During Pregnancy: A Population-based Study2013In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 98, no 7, 2687-2692 p.Article in journal (Refereed)
    Abstract [en]

    Context: There are international guidelines on thyroid function testing and management of hypothyroidism during pregnancy. Few studies have evaluated how they are implemented into clinical practice. Objective: In this descriptive study, we assessed the implementation of international guidelines in this field into local guidelines and also into clinical practice. Design and Participants: In a nationwide survey, all guidelines in Sweden were collected (n = 29), and the adherence of the local guidelines to The Endocrine Society Guidelines 2007 was evaluated. In a follow-up in 1 district, 5254 pregnant women with an estimated date of delivery between January 1, 2009, and December 31, 2011, were included for subsequent review of their medical reports. Results: All but 1 district had guidelines on the subject. All local guidelines included fewer than the 10 listed reasons for thyroid testing recommended by The Endocrine Society Guidelines. Furthermore, most guidelines recommended additional types of thyroid function tests to TSH sampling and lower trimester-specific TSH upper reference limits for women on levothyroxine treatment (P < .001). In the follow-up, the thyroid testing rate was 20%, with an overall frequency of women with trimester-specific elevated TSH of 18.5%. More than half of the women (50.9%) who were on levothyroxine treatment at conception had an elevated TSH level at thyroid testing according to The Endocrine Society Guidelines. Conclusions: The local guidelines are variable and poorly compliant with international guidelines. Performance of thyroid testing is not optimal, and rates of elevated TSH at testing are extremely high in subgroups.

  • 29.
    Granfors, Michaela
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Åkerud, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Skogö, Johan
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Wikström, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Sundström-Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Targeted Thyroid Testing During Pregnancy in Clinical Practice2014In: Obstetrics and Gynecology, ISSN 0029-7844, E-ISSN 1873-233X, Vol. 124, no 1, 10-15 p.Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE:To evaluate the efficacy of a targeted thyroid testing approach during pregnancy in clinical practice.

    METHODS:This is a retrospective cohort study performed within Uppsala County, Sweden. Data were derived from the population-based Uppsala Biobank of Pregnant Women, in which blood samples are collected in conjunction with the routine ultrasound screening in gestational week 17-19. For this study, 5,254 pregnant women with an estimated date of delivery between January 1, 2009, and December 31, 2011, were included. On review of their medical records, women who were tested for thyroid dysfunction during pregnancy in clinical practice were identified (n=891). From the remaining untested women, 1,006 women were randomly selected for analyses of thyrotropin (TSH), free thyroxine levels, and thyroid peroxidase antibodies. Thyroid-stimulating hormone levels in both groups were analyzed with regard to trimester-specific upper reference levels as recommended by the International Endocrine Society Guidelines.

    RESULTS:The proportion of trimester-specific TSH elevation was 12.6% in the targeted thyroid testing group and 12.1% in the untested group (P=.8; odds ratio [OR] 1.04, 95% confidence interval [CI] 0.79-1.37). The proportion of overt hypothyroidism was 1.1% and 0.7% in the groups, respectively (P=.4; OR 1.57, 95% CI 0.55-4.45).

    CONCLUSIONS:The prevalence of trimester-specific elevated TSH and overt hypothyroidism was equal in targeted thyroid tested and untested women. When implemented in clinical practice, targeted thyroid testing is unsatisfactory. If ongoing studies provide support for treatment of pregnant women with elevated TSH, universal thyroid testing appears the most reasonable approach.

  • 30.
    Gunnarsdottir, Johanna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Stephansson, Olof
    Cnattingius, Sven
    Akerud, Helena
    Wikström, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Risk of placental dysfunction disorders after prior miscarriages: a population-based study2014In: American Journal of Obstetrics and Gynecology, ISSN 0002-9378, E-ISSN 1097-6868, Vol. 211, no 1, 34.e1-34.e8 p.Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: The objective of the investigation was to study the association between prior miscarriages and the risks of placental dysfunction disorders, including preeclampsia, stillbirth, birth of a small for gestational age (SGA) infant, placental abruption, and spontaneous preterm birth. STUDY DESIGN: In a population-based cohort study including 619,587 primiparous women, we estimated risks of placental dysfunction disorders for women with 1 (n = 68,185), 2 (n = 11,410) and 3 or more (n = 3823) self-reported prior miscarriages. Risks were calculated as odds ratios by unconditional logistic regression analysis and adjustments were made for maternal age, early pregnancy body mass index, height, smoking habits, country of birth, years of formal education, in vitro fertilization, chronic hypertension, pregestational diabetes, hypothyroidism, systemic lupus erythematosis, fetal sex, and year of childbirth. RESULTS: Compared with women with no prior miscarriage, women with 1 prior miscarriage had almost no increased risks. Women with 2 prior miscarriages had increased risks of spontaneous preterm birth, preterm (<37 weeks) SGA infant, and placental abruption. The rates of all disorders were higher for women with 3 or more prior miscarriages compared with women without prior miscarriages: preeclampsia, 5.83% vs 4.27%; stillbirth, 0.69% vs 0.33%, SGA infant, 5.09% vs 3.22%, placental abruption, 0.81% vs 0.41%; and spontaneous preterm birth, 6.45% vs 4.40%. The adjusted odds ratios for preterm (<37 weeks) disorders in women with 3 prior miscarriages were approximately 2. CONCLUSION: History of 2 or more miscarriages is associated with an increased risk of placental dysfunction disorders and should be regarded as a risk factor in antenatal care.

  • 31. Gunnerbeck, Anna
    et al.
    Bonamy, Anna-Karin Edstedt
    Wikström, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Granath, Fredrik
    Wickstrom, Ronny
    Cnattingius, Sven
    Maternal Snuff Use and Smoking and the Risk of Oral Cleft Malformations - A Population-Based Cohort Study2014In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 1, e84715- p.Article in journal (Refereed)
    Abstract [en]

    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.

  • 32.
    Gunnerbeck, Anna
    et al.
    Department of Women's and Children's Health, Karolinska Institutet.
    Wikström, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Bonamy, Anna-Karin Edstedt
    Department of Women's and Children's Health, Karolinska Institutet.
    Wickström, Ronny
    Department of Women's and Children's Health, Karolinska Institutet.
    Cnattingius, Sven
    Clinical Epidemiology Unit, Department of Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
    Relationship of Maternal Snuff Use and Cigarette Smoking With Neonatal Apnea2011In: Pediatrics, ISSN 0031-4005, E-ISSN 1098-4275, Vol. 128, no 3, 503-509 p.Article in journal (Refereed)
    Abstract [en]

    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.

  • 33.
    Jonsson, Maria
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Cnattingius, Sven
    Department of Medicine, Clinical Epidemiology Unit, Karolinska Institute, Stockholm, Sweden.
    Wikström, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Elective induction of labor and the risk of cesarean section in low-risk parous women: a cohort study2013In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 92, no 2, 198-203 p.Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE:

    To estimate the association between elective induction of labor and cesarean section in low-risk parous women, and to assess if the association is influenced by induction method.

    DESIGN:

    Cohort study.

    SETTING:

    University hospital in Sweden. Population Parous women without pregnancy complications or previous cesarean section, and with a planned vaginal term (37-41 weeks), singleton birth, in vertex position were included.

    METHODS:

    Information was collected from a local database containing prospectively entered antenatal and delivery data. Odds ratios for cesarean section were calculated using generalized estimating equations logistic regression and adjusted for parity, maternal age, gestational length, birthweight, use of epidural anesthesia and year of birth.

    MAIN OUTCOME MEASURE:

    Emergency cesarean section.

    RESULTS:

    Among 7973 pregnancies that fulfilled the inclusion criteria, 343 (4%) had an elective induction of labor. Intravenous oxytocin was administered in 5% of these inductions, amniotomy was performed in 62%, and a cervical ripening agent was used in 33%. Electively induced labor more than doubled the risk of cesarean section compared with spontaneous labor onset (OR 2.5, 95% 1.4-4.2) and this risk was more than tripled when cervical ripening was used (OR 3.6, 95% confidence interval 1.7-7.6).

    CONCLUSIONS:

    In low-risk parous women, electively induced labor has an increased risk of emergency cesarean section compared with spontaneous onset labor. This risk increase is more pronounced if cervical ripening agents are required. Women need to be counseled about these risks before elective induction of delivery is decided.

  • 34.
    Junus, Katja
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Centlow, Magnus
    Lunds universitet, Medicinska fakulteten, Institutionen för kliniska vetenskaper, Lund, Avdelningen för obstetrik och gynekologi.
    Wikström, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Larsson, Irene
    Lunds universitet, Medicinska fakulteten, Institutionen för kliniska vetenskaper, Lund, Avdelningen för obstetrik och gynekologi.
    Hansson, Stefan R
    Lunds universitet, Medicinska fakulteten, Institutionen för kliniska vetenskaper, Lund, Avdelningen för obstetrik och gynekologi.
    Olovsson, Matts
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Gene expression profiling of placentae from women with early- and late-onset pre-eclampsia: down-regulation of the angiogenesis related genes ACVRL1 and EGFL7 in early-onset disease2012In: Molecular human reproduction, ISSN 1360-9947, E-ISSN 1460-2407, Vol. 18, no 3, 146-155 p.Article in journal (Refereed)
    Abstract [en]

    The underlying mechanisms behind the obstetric condition pre-eclampsia (PE) are still unclear. Manifestation of PE is heterogeneous and it has therefore been proposed to be a syndrome with different causes rather than one disease with a specific aetiology. Recently, we showed differences in circulating angiogenic factors between two subgroups - early- and late-onset PE. To further elucidate the differences between the two, we investigated placental gene expression profiles. Whole genome microarray technology and bioinformatic analysis were used to evaluate gene expression profiles in placentae from early- (24-32 gestational weeks, n=8) and late-onset (36-41 gestational weeks, n=7) PE. The results were verified by using quantitative real-time PCR. We found significant differences in the expression of 196 genes in early- compared with late-onset PE, 45 of these genes showing a fold change above 2. Bioinformatic analysis revealed alterations in angiogenesis and regulation of cell motility. Two angiogenesis-associated transcripts (Egfl7 and Acvrl1) showed lower expression in early-onset PE vs. late-onset PE (p=0.037 and p=0.003) and vs. gestational age-matched controls (p=0.007 and p=0.011). We conclude that angiogenesis-associated genes are regulated in a different manner in the two subgroups, and that the gene expression profiles of early- and late-onset PE diverge, supporting the hypothesis of early- and late-onset PE being at least partly two separate entities.

  • 35.
    Junus, Katja
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Wikström, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Olovsson, Matts
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Early second-trimester plasma levels of NT-proBNP in women who subsequently develop early-onset preeclampsia2017In: The Journal of Maternal-Fetal & Neonatal Medicine, ISSN 1476-7058, E-ISSN 1476-4954, Vol. 30, no 18, 2163-2165 p.Article in journal (Refereed)
    Abstract [en]

    Plasma levels of NT-proBNP are elevated in women with preeclampsia at the time of diagnosis. The objective of this case-control study was to evaluate N-terminal proBNP (NT-proBNP) in maternal plasma as an early second-trimester biomarker for prediction of early-onset preeclampsia. In early second-trimester samples, women who later developed preeclampsia at gestational age 34 wk + 0 or earlier (n = 16) had similar plasma levels of NT-proBNP (median 51.8, range 26.1-131.9 pg/ml) as women with uncomplicated pregnancy outcomes (n = 43) (53.0, 14.9-184.2 pg/ml). The early second-trimester level of NT-proBNP cannot therefore be used as a predictive biomarker of early-onset preeclampsia.

  • 36.
    Junus, Katja
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Wikström, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Olovsson, Matts
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Placental Expression of proBNP/NT-proBNP and Plasma Levels of NT-proBNP in Early- and Late-Onset Preeclampsia2014In: American Journal of Hypertension, ISSN 0895-7061, E-ISSN 1941-7225, Vol. 27, no 9, 1225-1230 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Levels of plasma N-terminal pro B-type natriuretic peptide (NT-proBNP) are elevated in preeclampsia. In this study, the possibility that the placenta produces and releases proBNP/NT-proBNP was explored. Plasma levels of NT-proBNP in early- and late-onset preeclampsia were also measured.

    METHODS: Placental proBNP mRNA in early-onset preeclampsia (n = 7), late-onset preeclampsia (n = 8), and controls of similar gestational age (n = 10) was assessed by quantitative real-time polymerase chain reaction. ProBNP/NT-proBNP protein was studied in placental samples with immunohistochemistry (n = 8) and tissue culture (n = 2). Plasma levels of NT-proBNP were measured in early-onset preeclampsia (n = 18), late-onset preeclampsia (n = 20), and relevant controls (n = 36).

    RESULTS: Transcripts of proBNP mRNA were found in 20 out of 25 samples, there were no differences in expression between the groups. ProBNP/NT-proBNP protein was observed in maternal spiral arteries and in syncytiotrophoblasts in all placental samples. After placental tissue culture, there were measurable amounts of NT-proBNP in the culture media. Women with both early- (365 [14-9815] pg/ml) and late-onset preeclampsia (176 [33-2547] pg/ml) had higher levels of NT-proBNP than their controls (P < 0.001). There was a tendency toward higher levels of NT-proBNP in women with early-onset preeclampsia than in women with late-onset preeclampsia (P = 0.057).

    CONCLUSION: The results indicate possible placental production and release of proBNP/NT-proBNP into the maternal circulation.

  • 37.
    Katja, Junus
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Anna-Karin, Wikström
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Anders, Larsson
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Olovsson, Matts
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    PP015. Plasma levels and placental expression of BNP/NT-proBNP in early and late onset preeclampsia2013In: Pregnancy Hypertension, ISSN 2210-7789, E-ISSN 2210-7797, Vol. 3, no 2, 73- p.Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION:

    Women with preeclampsia (PE) have elevated plasma levels of NT-proBNP. We hypothesized that the placenta may be a source to these elevated levels.

    OBJECTIVES:

    Our objectives were to study the plasma levels of NT-proBNP and the protein and mRNA expression of placental BNP in women with early and late onset PE and controls.

    METHODS:

    Plasma levels of NT-proBNP were measured in women with early (n=18) and late (n=20) onset PE, in two groups of healthy pregnant women in gestational week 24-32 (n=22) and 36-42 (n=14), and in non-pregnant women (n=20). Placental BNP protein and mRNA was studied with immunohistochemistry and qPCR. Placental release of NT-proBNP was studied with tissue culturing.

    RESULTS:

    Women with early (365 (14-9815) pg/ml) and late (176 (33-2547) pg/ml) onset PE had higher levels of NT-proBNP in plasma than their respective controls (p<0.001). A tendency towards higher plasma levels in early compared to late onset PE was observed (p=0.057). 20 out of 25 placental tissue samples had proBNP mRNA, no differences between the study groups were found. BNP protein was found in maternal spiral arteries and syncytiotrophoblasts. NT-proBNP peptide (6-7pg/ml) was present in medium used for placenta cultures.

    CONCLUSIONS:

    Our results suggest that there may be a placental source of NT-proBNP. If this source is responsible for the elevated plasma levels of NT-proBNP in preeclamptic women and what role, if any, BNP/NT-proBNP play in PE pathophysiology remains to be elucidated.

  • 38.
    Lagerros, Ylva Trolle
    et al.
    Unit of Clinical Epidemiology, Department of Medicine, Karolinska Institutet, T2, Stockholm, Sweden.
    Cnattingius, Sven
    Unit of Clinical Epidemiology, Department of Medicine, Karolinska Institutet, T2, Stockholm, Sweden.
    Granath, Fredrik
    Unit of Clinical Epidemiology, Department of Medicine, Karolinska Institutet, T2, Stockholm, Sweden.
    Hanson, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Wikström, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    From infancy to pregnancy: birth weight, body mass index, and the risk of gestational diabetes2012In: European Journal of Epidemiology, ISSN 0393-2990, E-ISSN 1573-7284, Vol. 27, no 10, 799-805 p.Article in journal (Refereed)
    Abstract [en]

    Obesity is a risk factor for gestational diabetes, whereas the role of the mother's birth weight is more uncertain. We aimed to investigate the combined effect of mothers' birth-weight-for-gestational-age and early pregnancy Body Mass Index (BMI) in relation to risk of gestational diabetes. Between 1973 and 2006, we identified a cohort of 323,083 women included in the Swedish Medical Birth Register both as infants and as mothers. Main exposures were mothers' birth-weight-for-gestational-age (categorized into five groups according to deviation from national mean birth weight) and early pregnancy BMI (classified according to WHO). Rates of gestational diabetes increased with adult BMI, independently of birth-weight-for-gestational-age. However, compared to women with appropriate birth-weight-for-gestational-age [appropriate-for-gestational age (AGA); -1 to +1 SD] and BMI (<25.0), women with obesity class II-III (BMI ≥ 35.0) had an adjusted odds ratio (OR) of 28.7 (95 % confidence interval, CI 17.0-48.6) for gestational diabetes if they were born small-for-gestational-age [small for gestational age (SGA); <-2SD], OR = 20.3 (95 % CI 11.8-34.7) if born large-for-gestational-age [large-for-gestational-age (LGA); >2SD], and OR = 10.4 (95 % CI 8.4-13.0) if born AGA. Risk of gestational diabetes is not only increased among obese women, but also among women born SGA and LGA. Severely obese women born with a low or a high birth-weight-for-gestational-age seem more vulnerable to the development of gestational diabetes compared to normal weight women. Normal pre-pregnancy BMI diminishes the increased risk birth size may confer in terms of gestational diabetes. Therefore, the importance of keeping a healthy weight cannot be overemphasized.

  • 39. Laszlo, K. D.
    et al.
    Ananth, C. V.
    Wikström, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Svensson, T.
    Li, J.
    Olsen, J.
    Vestergaard, M.
    Obel, C.
    Cnattingius, S.
    Loss of a close family member the year before or during pregnancy and the risk of placental abruption: a cohort study from Denmark and Sweden2014In: Psychological Medicine, ISSN 0033-2917, E-ISSN 1469-8978, Vol. 44, no 9, 1855-1866 p.Article in journal (Refereed)
    Abstract [en]

    Background Maternal stress during pregnancy is associated with a modestly increased risk of fetal growth restriction and pre-eclampsia. Since placental abruption shares similar pathophysiological mechanisms and risk factors with fetal growth restriction and pre-eclampsia, we hypothesized that maternal stress may be implicated in abruption risk. We investigated the association between maternal bereavement during pregnancy and placental abruption. Method We studied singleton births in Denmark (1978-2008) and Sweden (1973-2006) (n=5103272). In nationwide registries, we obtained data on death of women's close family members (older children, siblings, parents, and partners), abruption and potential confounders. Results A total of 30312 (6/1000) pregnancies in the cohort were diagnosed with placental abruption. Among normotensive women, death of a child the year before or during pregnancy was associated with a 54% increased odds of abruption [95% confidence interval (CI) 1.30-1.82]; the increased odds were restricted to women who lost a child the year before or during the first trimester in pregnancy. In the group with chronic hypertension, death of a child the year before or in the first trimester of pregnancy was associated with eight-fold increased odds of abruption (odds ratio 8.17, 95% CI 3.17-21.10). Death of other relatives was not associated with abruption risk. Conclusions Loss of a child the year before or in the first trimester of pregnancy was associated with an increased risk of abruption, especially among women with chronic hypertension. Studies are needed to investigate the effect of less severe, but more frequent, sources of stress on placental abruption risk.

  • 40. Laszlo, Krisztina D.
    et al.
    Liu, Xiao Qin
    Svensson, Tobias
    Wikström, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Li, Jiong
    Olsen, Jørn
    Obel, Carsten
    Vestergaard, Mogens
    Cnattingius, Sven
    Psychosocial Stress Related to the Loss of a Close Relative the Year Before or During Pregnancy and Risk of Preeclampsia2013In: Hypertension, ISSN 0194-911X, E-ISSN 1524-4563, Vol. 62, no 1, 183-189 p.Article in journal (Refereed)
    Abstract [en]

    The role of stress in the pathogenesis of preeclampsia has only been investigated in a few studies, and the findings are not conclusive. We analyzed whether maternal bereavement shortly before or during pregnancy is associated with an increased risk of preeclampsia. We conducted a cohort study of singleton births in Denmark during 1978-2008 and in Sweden during 1973-2006 (n=4 122 490) by linking national population-based registers. Mothers were considered exposed to bereavement if they lost a parent, a sibling, a partner, or a child the year before or during pregnancy (n=124 553). The risk of preeclampsia was slightly increased for women who lost a close relative during the 6 months before conception (odds ratio [OR], 1.14; 95% confidence interval [CI], 1.06-1.23) or during the first trimester of pregnancy (OR, 1.15; 95% CI, 1.03-1.29). Exposure during these periods tended to be more closely related to early preeclampsia (delivery before 34 weeks of gestation; OR, 1.37; 95% CI, 1.12-1.67) than to late preeclampsia (OR, 1.13; 95% CI, 1.06-1.20). The strongest association was observed between loss of a child and early preeclampsia when the exposure window was from 6 months before pregnancy until start of second trimester (OR, 4.03; 95% CI, 2.46-6.61). Our results related to timing of exposure suggest that severe stress may influence early placentation. However, the public health implications of our findings are limited in populations with a low prevalence of severe stress exposures.

  • 41.
    Liljeström, Lena
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Wikström, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Hanson, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Åkerud, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Jonsson, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Evaluation of the discrepancy between pH and lactate in combined fetal scalp blood sampling2011In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 90, no 10, 1088-1093 p.Article in journal (Refereed)
    Abstract [en]

    Objective. To evaluate the rate of discrepancy between pH and lactate values in fetal blood sampling (FBS). To evaluate differences in obstetric management in response to combined tests (pH and lactate) and single tests (pH or lactate).

    Design. Descriptive study.

    Setting. Uppsala University Hospital, Sweden. Population. Labors monitored by FBS during one year (n=241).

    Methods. Discrepancy in the combined tests was defined as a test having one abnormal and one normal value. Abnormal pH was defined as 7.24 or lower and abnormal lactate as 4.2 or higher. The results were categorized according to whether the test was normal or abnormal and according to whether it was a combined or single analysis. Main outcome measures. Discrepancy between pH and lactate values in combined tests. Frequency of operative delivery for fetal distress (ODFD). Time interval from the last FBS to ODFD.

    Results. In the combined tests with abnormality, a discrepancy between pH and lactate values occurred in 55%. The mean time interval from the last FBS to ODFD was longer in combined tests with one abnormal compared with two abnormal test results, 75 vs. 37 minutes (p<0.05). Operative delivery for fetal distress was performed less often after combined tests than after single tests: 41/62 (66%) vs. 19/20 (95%) (p<0.05).

    Conclusion. In the combined test, discrepancies were common and occurred in half of the samples with an abnormality. Obstetric management was influenced by the discrepancy between test results with respect to ODFD rates and the time interval from the last FBS to delivery.

  • 42.
    Liljeström, Lena
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Wikström, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Skalkidou, Alkistis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Åkerud, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Jonsson, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Experience of fetal scalp blood sampling during labor2014In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 93, no 1, 113-117 p.Article in journal (Refereed)
    Abstract [en]

    Fetal scalp blood sampling (FBS) is often claimed to be painful for women in labor and difficult for obstetricians to perform. Our aim was to assess women's experience of pain during FBS and obstetricians' experience of difficulty in performing the test. At a tertiary centre in Sweden, a questionnaire with answers on a ten-point scale was completed by 51 women and by the obstetricians performing the test. Women's experience of pain had a median of 3.5. FBS was well tolerated in women who had epidural analgesia, but might be associated with pain in women without. Higher maternal body mass index and less cervical dilatation were associated with higher pain ratings. Obstetricians did not generally experience scalp sampling as difficult to perform (median score 3.0). However, the sampling procedure can be more complicated in situations with higher maternal body mass, less cervical dilatation, and a higher station of the fetal head. 

  • 43.
    Lindam, Anna
    et al.
    Karolinska Inst, Stockholm, Sweden..
    Johansson, Stefan
    Karolinska Inst, Stockholm, Sweden.;Karolinska Inst, Soder Sjukhuset, Dept Clin Sci & Educ, Stockholm, Sweden..
    Stephansson, Olof
    Karolinska Inst, Stockholm, Sweden.;Univ Calif Berkeley, Sch Publ Hlth, Div Epidemiol, Berkeley, CA 94720 USA..
    Wikström, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology. Karolinska Inst, Stockholm, Sweden..
    Cnattingius, Sven
    Dept Med, Clin Epidemiol Unit, Solna, Sweden.;Karolinska Inst, Stockholm, Sweden..
    High Maternal Body Mass Index in Early Pregnancy and Risks of Stillbirth and Infant Mortality-A Population-Based Sibling Study in Sweden2016In: American Journal of Epidemiology, ISSN 0002-9262, E-ISSN 1476-6256, Vol. 184, no 2, 98-105 p.Article in journal (Refereed)
    Abstract [en]

    In a population-based case-control study, we investigated whether familial confounding influenced the associations between maternal overweight/obesity and risks of stillbirth and infant mortality by including both population and sister controls. Using nationwide data from the Swedish Medical Birth Register (1992-2011), we included all primiparous women with singleton births who also had a sister with a first birth during that time period. We used logistic regression analyses to calculate odds ratios (and 95% confidence intervals) adjusted for maternal age, height, smoking habits, education, and time period (5-year groups) of child's birth. Body mass index (BMI) was calculated as weight (kg)/height (m)(2). Compared with population controls with a normal BMI (18.5-24.9), stillbirth risk increased with increasing BMI (BMI 25-29.9: odds ratio (OR) = 1.51 (95% confidence interval (CI): 1.21, 1.89); BMI 30-34.9: OR = 1.77 (95% CI: 1.24, 2.50); BMI a parts per thousand yen35: OR = 3.16 (95% CI: 2.10, 4.76)). The sister case-control analyses revealed similar results. Offspring of obese women (BMI a parts per thousand yen30) had an increased risk of infant mortality when population controls were used (OR = 2.41, 95% CI: 1.83, 3.16), and an even higher risk was obtained when sister controls were used (OR = 4.04, 95% CI: 2.25, 7.25). We conclude that obesity in early pregnancy is associated with increased risks of stillbirth and infant mortality independently of genetic and early environmental risk factors shared within families.

  • 44.
    Lindström, Linda
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Skjaerven, Rolv
    Univ Bergen, Norwegian Inst Publ Hlth, Med Birth Registry Norway, Dept Global Publ Hlth & Primary Care, Bergen, Norway..
    Bergman, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Lundgren, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Klungsøyr, Kari
    Univ Bergen, Norwegian Inst Publ Hlth, Med Birth Registry Norway, Dept Global Publ Hlth & Primary Care, Bergen, Norway..
    Cnattingius, Sven
    Karolinska Univ Hosp, Karolinska Inst, Dept Med Solna, Clin Epidemiol Unit, Stockholm, Sweden..
    Wikström, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. Karolinska Univ Hosp, Karolinska Inst, Dept Med Solna, Clin Epidemiol Unit, Stockholm, Sweden..
    Chronic hypertension in women after perinatal exposure to preeclampsia, being born small for gestational age or preterm2017In: Paediatric and Perinatal Epidemiology, ISSN 0269-5022, E-ISSN 1365-3016, Vol. 31, no 2, 89-98 p.Article in journal (Refereed)
    Abstract [en]

    Background: There is an established association between adverse events during perinatal life and chronic hypertension in adult life. However, disadvantageous conditions often coexist in the same pregnancy. We investigated single and joint perinatal exposure to preeclampsia, being born small for gestational age (SGA) or preterm and subsequent risk of chronic hypertension.

     

    Methods: The study population consisted of 731,008 primiparous women from Norway and Sweden registered in the Medical Birth Registers, both as infants and as first time mothers between 1967-2009 (Norway) and 1973-2010 (Sweden). Risk of chronic hypertension in early pregnancy was calculated in women perinatally exposed to preeclampsia, born SGA or preterm by log-binominal regression analysis, and adjusted for maternal age and level of education in the 1st generation.

     

    Results: The rate of chronic hypertension was 0.4%. Risk of chronic hypertension was associated with single perinatal exposure to preeclampsia, being born SGA or preterm with adjusted relative risks (95% confidence intervals, CI) 2.2 (95% CI 1.8, 2.7), 1.1 (95% CI 1.0, 1.3) and 1.3 (95% CI 1.0, 1.5) respectively. The risks increased after joint exposures, with an almost 4-fold risk increase after perinatal exposure to preeclampsia and preterm birth. Additional adjustment for BMI and smoking in the 2nd generation in a subset of the cohort only had a minor impact on the results.

     

    Conclusions: Perinatal exposure to preeclampsia, being born SGA or preterm is independently associated with increased risk of chronic hypertension. The highest risk was seen after exposure to preeclampsia, especially if combined with SGA or preterm birth.

    The full text will be freely available from 2018-03-19 20:09
  • 45.
    Lovvik, T. S.
    et al.
    Norwegian Univ Sci & Technol, Inst Lab Med Childrens & Womens Hlth, N-7034 Trondheim, Norway.;St Olavs Hosp, Dept Obstet & Gynaecol, N-7006 Trondheim, Norway..
    Wikström, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology. Karolinska Inst, Clin Epidemiol Unit, Dept Med, Stockholm, Sweden..
    Neovius, M.
    Karolinska Inst, Clin Epidemiol Unit, Dept Med, Stockholm, Sweden..
    Stephansson, O.
    Karolinska Inst, Clin Epidemiol Unit, Dept Med, Stockholm, Sweden.;Karolinska Inst, Div Obstet & Gynaecol, Dept Womens & Childrens Hlth, Stockholm, Sweden..
    Roos, N.
    Karolinska Inst, Clin Epidemiol Unit, Dept Med, Stockholm, Sweden.;Karolinska Inst, Div Obstet & Gynaecol, Dept Womens & Childrens Hlth, Stockholm, Sweden..
    Vanky, E.
    Norwegian Univ Sci & Technol, Inst Lab Med Childrens & Womens Hlth, N-7034 Trondheim, Norway.;St Olavs Hosp, Dept Obstet & Gynaecol, N-7006 Trondheim, Norway..
    Pregnancy and perinatal outcomes in women with polycystic ovary syndrome and twin births: a population-based cohort study2015In: British Journal of Obstetrics and Gynecology, ISSN 1470-0328, E-ISSN 1471-0528, Vol. 122, no 10, 1295-1302 p.Article in journal (Refereed)
    Abstract [en]

    Objective:To investigate pregnancy and perinatal outcomes in twin births among women with and without polycystic ovary syndrome (PCOS) diagnosis. Design: Population-based cohort study. Setting: Sweden. Population: We identified 20965 women with twin births between 1995 and 2009 of whom 226 had a PCOS diagnosis through linkage between the Swedish Medical Birth Register and the Swedish National Patient Register. Methods: Calculating risk ratios (RR) with 95% confidence intervals (CI) using a log-binomial regression model and hazard ratios (HR) with 95% CI for preterm birth. Main outcome measures: Preterm birth, low birthweight, caesarean section, pre-eclampsia, Apgar score <7 at 5minutes and perinatal mortality. Results: PCOS diagnosis in twin pregnancy was associated with increased risk of preterm delivery (51% versus 43%, RR 1.18 [95% CI 1.03-1.37]), particularly spontaneous preterm delivery (37% versus 28%; RR 1.30 [95% CI 1.09-1.55]) and very preterm birth (<32weeks) (14% versus 8%, RR 1.62 [95% CI 1.10-2.37]). Twins of PCOS mothers had more often low birthweight (48% versus 39%, adjusted RR 1.40 [95% CI 1.09-1.80]). This difference disappeared when adjusting for gestational age. No risk difference was found for caesarean section, pre-eclampsia, low 5-minute Apgar score or perinatal mortality. Conclusions: The risk of preterm delivery in twin pregnancies is increased by having a PCOS diagnosis. This should be considered in risk estimation and antenatal follow-up of twin pregnancies.

  • 46.
    Maghsoudlou, Siavash
    et al.
    Karolinska Inst, Dept Med Solna, Clin Epidemiol Unit, S-17176 Stockholm, Sweden.;Golestan Univ Med Sci, Fac Med, Gorgan, Scandinavia..
    Cnattingius, Sven
    Karolinska Inst, Dept Med Solna, Clin Epidemiol Unit, S-17176 Stockholm, Sweden..
    Aarabi, Mohsen
    Mazandaran Univ Med Sci, Fac Med, Sari, Iran..
    Montgomery, Scott M.
    Karolinska Inst, Dept Med Solna, Clin Epidemiol Unit, S-17176 Stockholm, Sweden.;Orebro Univ Hosp, Clin Epidemiol & Biostat, Orebro, Sweden.;Univ Orebro, SE-70182 Orebro, Sweden.;UCL, Res Dept Epidemiol & Publ Hlth, London, England..
    Semnani, Shahriar
    Golestan Univ Med Sci, Fac Med, Gorgan, Scandinavia..
    Stephansson, Olof
    Karolinska Inst, Dept Med Solna, Clin Epidemiol Unit, S-17176 Stockholm, Sweden.;Karolinska Univ Hosp & Inst, Dept Womens & Childrens Hlth, Div Obstet & Gynecol, Stockholm, Sweden..
    Wikström, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology. Karolinska Inst, Dept Med Solna, Clin Epidemiol Unit, S-17176 Stockholm, Sweden..
    Bahmanyar, Shahram
    Golestan Univ Med Sci, Fac Med, Gorgan, Scandinavia.;Karolinska Inst, Clin Epidemiol Unit, S-17176 Stockholm, Sweden.;Karolinska Inst, Ctr Pharmacoepidemiol, Dept Med, S-17176 Stockholm, Sweden..
    Consanguineous marriage, prepregnancy maternal characteristics and stillbirth risk: a population-based case-control study2015In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 94, no 10, 1095-1101 p.Article in journal (Refereed)
    Abstract [en]

    Introduction. Consanguineous marriage is associated with increased risks for congenital anomalies, low birthweight, and other adverse perinatal outcomes. In this population-based, case-control study we investigated the association between consanguineous marriage (first-cousin marriage) and stillbirth risk, using prospectively collected information from prepregnancy visits. Material and methods. From 2007 to 2009, we identified 283 stillbirths (cases) and 2088 randomly selected live control births through prepregnancy visits in rural Golestan, Iran. The associations between consanguinity and prepregnancy maternal characteristics and stillbirth risk were examined using multivariate logistic regression. Results. The rate of consanguineous marriage was 19.4% among cases and 13.6% among controls. Consanguinity was associated with increased stillbirth risk [ odds ratio (OR) 1.53; 95% CI 1.10-2.14]. The association was significantly increased for preterm stillbirth (< 37 gestational weeks) (OR 2.43; 95% CI 1.46-4.04) but not for term stillbirth (>= 37 weeks) (OR 1.14; 95% CI 0.75-1.74). Low and high maternal age, underweight, obesity, nulliparity, a history of infertility or miscarriage, previous obstetric complications (preeclampsia, preterm delivery, and stillbirth in previous pregnancies) were also associated with increased stillbirth risks. Conclusions. Consanguineous marriage is associated with increased risk of stillbirth, particularly preterm stillbirth. Findings for other maternal risk factors for stillbirth in rural Iran are consistent with previously reported findings from high-income countries.

  • 47.
    Maghsoudlou, Siavash
    et al.
    Karolinska Inst, Clin Epidemiol Unit, Dept Med, Solna, Sweden..
    Cnattingius, Sven
    Karolinska Inst, Clin Epidemiol Unit, Dept Med, Solna, Sweden..
    Montgomery, Scott
    Karolinska Inst, Clin Epidemiol Unit, Dept Med, Solna, Sweden.;Orebro Univ, Clin Epidemiol & Biostat, Sch Med Sci, Orebro, Sweden.;UCL, Dept Epidemiol & Publ Hlth, London, England..
    Aarabi, Mohsen
    Mazandaran Univ Med Sci, Fac Med, Sari, Iran..
    Semnani, Shahriar
    Golestan Univ Med Sci, Fac Med, Gorgan, Iran..
    Wikström, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. Karolinska Inst, Clin Epidemiol Unit, Dept Med, Solna, Sweden..
    Bahmanyar, Shahram
    Karolinska Inst, Clin Epidemiol Unit, Dept Med, Solna, Sweden.;Karolinska Inst, Ctr Pharmacoepidemiol, Dept Med, Solna, Sweden..
    Opium use during pregnancy and risk of preterm delivery: A population-based cohort study2017In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 4, e0176588Article in journal (Refereed)
    Abstract [en]

    Background Use of narcotic or "recreational" drugs has been associated with adverse pregnancy outcomes such as preterm delivery. However, the associations might be confounded by other factors related to high-risk behaviours. This is the first study to investigate the association between traditional opium use during pregnancy and risk of preterm delivery. Method and findings We performed a population-based cohort study in the rural areas of the Golestan province, Iran between 2008 and 2010. We randomly selected 920 women who used (usually smoked) opium during pregnancy and 920 women who did not. Logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI) for the associations between the opium use during pregnancy and preterm delivery and adjustment was made for potential confounding factors. This study shows compared with non-use of opium and tobacco, use of only opium during pregnancy was associated with an increased risk of preterm delivery (OR = 1.56; 95% CI 1.05-2.32), and the risk was more than two-fold increased among dual users of opium and tobacco (OR = 2.31; 95% CI 1.37-3.90). We observed that opium use only was associated with a doubled risk for preterm caesarean delivery (OR = 2.05; 95% CI 1.10-3.82) but not for preterm vaginal delivery (OR = 1.25; 95% CI 0.75-2.07). Dual use of opium and tobacco was associated with a substantially increased risk of vaginal preterm delivery (OR = 2.58; 95% CI 1.41-4.71). Conclusions Opium use during pregnancy among non-tobacco smokers is associated with an increased risk of preterm caesarean delivery, indicating an increased risk of a compromised foetus before or during labour. Women who use both opium and smoked during pregnancy have an increased risk of preterm vaginal delivery, indicating an increased risk of spontaneous preterm delivery.

  • 48.
    Moldeus, Karolina
    et al.
    Karolinska Univ Hosp & Inst, Dept Med Solna, Clin Epidemiol Unit, Stockholm, Sweden.;Visby Hosp, Dept Obstet & Gynecol, Visby, Sweden..
    Cheng, Yvonne W.
    Univ Calif Davis, Dept Surg, Davis, CA 95616 USA.;Calif Pacific Med Ctr, Dept Obstet & Gynecol, San Francisco, CA USA..
    Wikström, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Obstetric research. Karolinska Univ Hosp & Inst, Dept Med Solna, Clin Epidemiol Unit, Stockholm, Sweden.
    Stephansson, Olof
    Karolinska Univ Hosp & Inst, Dept Med Solna, Clin Epidemiol Unit, Stockholm, Sweden.;Karolinska Inst, Div Obstet & Gynecol, Dept Womens & Childrens Hlth, Stockholm, Sweden..
    Induction of labor versus expectant management of large-for-gestational-age infants in nulliparous women2017In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 7, e0180748Article in journal (Refereed)
    Abstract [en]

    Background There is no apparent consensus on obstetric management, i.e., induction of labor or expectant management of women with suspected large-for-gestational-age (LGA)-fetuses. Methods and findings To further examine the subject, a nationwide population-based cohort study from the Swedish Medical Birth Register in nulliparous non-diabetic women with singleton, vertex LGA (> 90 th centile) births, 1992-2013, was performed. Delivery of a live-born LGA infant induced at 38 completed weeks of gestation in non-preeclamptic pregnancies, was compared to those of expectant management, with delivery at 39, 40, 41, or 42 completed weeks of gestation and beyond, either by labor induction or via spontaneous labor. Primary outcome was mode of delivery. Secondary outcomes included obstetric anal sphincter injury, 5-minute Apgar< 7 and birth injury. Multivariable logistic regression analysis was performed to control for potential confounding. We found that among the 722 women induced at week 38, there was a significantly increased risk of cesarean delivery (aOR = 1.44 95% CI: 1.20-1.72), compared to those with expectant management (n = 44 081). There was no significant difference between the groups in regards to risk of instrumental vaginal delivery (aOR = 1.05, 95% CI: 0.85-1.30), obstetric anal sphincter injury (aOR = 0.81, 95% CI: 0.55-1.19), nor 5minute Apgar<7 (aOR = 1.06, 95% CI: 0.58-1.94) or birth injury (aOR = 0.82, 95% CI: 0.49- 1.38). Similar comparisons for induction of labor at 39, 40 or 41 weeks compared to expectant management with delivery at a later gestational age, showed increased rates of cesarean delivery for induced women. Conclusions In women with LGA infants, induction of labor at 38 weeks gestation is associated with increased risk of cesarean delivery compared to expectant management, with no difference in neonatal morbidity.

  • 49.
    Nelander, Maria
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Cnattingius, S
    Åkerud, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Pedersen, N L
    Wikström, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Pregnancy hypertensive disease and risk of dementia and cardiovascular disease in women aged 65 years or older: a cohort study2016In: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 6, no 1, e009880Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: The primary aim was to study pregnancy hypertensive disease and subsequent risk of dementia. The second aim was to study if the increased risks of cardiovascular disease (CVD) and stroke after pregnancy hypertensive disease persist in an elderly population.

    DESIGN: Cohort study.

    SETTING: Sweden.

    POPULATION OR SAMPLE: 3232 women 65 years or older (mean 71 years) at inclusion.

    METHODS: Cox proportional hazards regression analyses were used to calculate risks of dementia, CVD and/or stroke for women exposed to pregnancy hypertensive disease. Exposure data were collected from an interview at inclusion during the years 1998-2002. Outcome data were collected from the National Patient Register and Cause of Death Register from the year of inclusion until the end of 2010. Age at inclusion was set as a time-dependent variable, and adjustments were made for body mass index, education and smoking.

    MAIN OUTCOME MEASURES: Dementia, CVD, stroke.

    RESULTS: During the years of follow-up, 7.6% of the women exposed to pregnancy hypertensive disease received a diagnosis of dementia, compared with 7.4% among unexposed women (HR 1.19; 95% CI 0.79 to 1.73). The corresponding rates for CVD were 22.9% for exposed women and 19.0% for unexposed women (HR 1.29; 95% CI 1.02 to 1.61), and for stroke 13.4% for exposed women and 10.7% for unexposed women (HR 1.36; 95% CI 1.00 to 1.81).

    CONCLUSIONS: There was no increased risk of dementia after self-reported pregnancy hypertensive disease in our cohort. We found that the previously reported increased risk of CVD and stroke after pregnancy hypertensive disease persists in an older population.

  • 50.
    Nelander, Maria
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Obstetric research.
    Weis, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Bergman, Lina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Center for Clinical Research Dalarna. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Obstetric research.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Wikström, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Obstetric research. Karolinska Inst, Danderyd Hosp, Dept Clin Sci, Stockholm, Sweden.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Cerebral Magnesium Levels in Preeclampsia; A Phosphorus Magnetic Resonance Spectroscopy Study2017In: American Journal of Hypertension, ISSN 0895-7061, E-ISSN 1941-7225, Vol. 30, no 7, 667-672 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Magnesium sulfate (MgSO4) is used as a prophylaxis for eclamptic seizures. The exact mechanism of action is not fully established. We used phosphorus magnetic resonance spectroscopy (31P-MRS) to investigate if cerebral magnesium (Mg2+) levels differ between women with preeclampsia, normal pregnant, and nonpregnant women.

    METHODS: This cross-sectional study comprised 28 women with preeclampsia, 30 women with normal pregnancies in corresponding gestational week (range: 23-41 weeks) and 11 nonpregnant healthy controls. All women underwent 31P-MRS from the parieto-occipital region of the brain and were interviewed about cerebral symptoms. Differences between groups were assessed by analysis of variance and Tukey's post-hoc test. Correlations between Mg2+ levels and specific neurological symptoms were estimated with Spearman's rank test.

    RESULTS: Mean maternal cerebral Mg2+ levels were lower in women with preeclampsia (0.12 mM ± 0.02) compared to normal pregnant controls (0.14 mM ± 0.03) (P = 0.04). Nonpregnant and normal pregnant women did not differ in Mg2+ levels. Among women with preeclampsia, lower Mg2+ levels correlated with presence of visual disturbances (P = 0.04). Plasma levels of Mg2+ did not differ between preeclampsia and normal pregnancy.

    CONCLUSIONS: Women with preeclampsia have reduced cerebral Mg2+ levels, which could explain the potent antiseizure prophylactic properties of MgSO4. Within the preeclampsia group, women with visual disturbances have lower levels of Mg2+ than those without such symptoms.

12 1 - 50 of 71
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