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1.
  • Abel, Marianne Hope, et al. (författare)
  • Insufficient maternal iodine intake is associated with subfecundity, reduced foetal growth, and adverse pregnancy outcomes in the Norwegian Mother, Father and Child Cohort Study.
  • 2020
  • Ingår i: BMC medicine. - : Springer Science and Business Media LLC. - 1741-7015. ; 18:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Severe iodine deficiency impacts fertility and reproductive outcomes. The potential effects of mild-to-moderate iodine deficiency are not well known. The aim of this study was to examine whether iodine intake was associated with subfecundity (i.e. > 12 months trying to get pregnant), foetal growth, and adverse pregnancy outcomes in a mild-to-moderately iodine-deficient population.We used the Norwegian Mother, Father and Child Cohort Study (MoBa) and included 78,318 pregnancies with data on iodine intake and pregnancy outcomes. Iodine intake was calculated using an extensive food frequency questionnaire in mid-pregnancy. In addition, urinary iodine concentration was available in a subsample of 2795 pregnancies. Associations were modelled continuously by multivariable regression controlling for a range of confounding factors.The median iodine intake from food was 121 μg/day and the median urinary iodine was 69 μg/L, confirming mild-to-moderate iodine deficiency. In non-users of iodine supplements (n = 49,187), low iodine intake (< 100-150 μg/day) was associated with increased risk of preeclampsia (aOR = 1.14 (95% CI 1.08, 1.22) at 75 vs. 100 μg/day, p overall < 0.001), preterm delivery before gestational week 37 (aOR = 1.10 (1.04, 1.16) at 75 vs. 100 μg/day, p overall = 0.003), and reduced foetal growth (- 0.08 SD (- 0.10, - 0.06) difference in birth weight z-score at 75 vs. 150 μg/day, p overall < 0.001), but not with early preterm delivery or intrauterine death. In planned pregnancies (n = 56,416), having an iodine intake lower than ~ 100 μg/day was associated with increased prevalence of subfecundity (aOR = 1.05 (1.01, 1.09) at 75 μg/day vs. 100 μg/day, p overall = 0.005). Long-term iodine supplement use (initiated before pregnancy) was associated with increased foetal growth (+ 0.05 SD (0.03, 0.07) on birth weight z-score, p < 0.001) and reduced risk of preeclampsia (aOR 0.85 (0.74, 0.98), p = 0.022), but not with the other adverse pregnancy outcomes. Urinary iodine concentration was not associated with any of the dichotomous outcomes, but positively associated with foetal growth (n = 2795, p overall = 0.017).This study shows that a low iodine intake was associated with restricted foetal growth and a higher prevalence of preeclampsia in these mild-to-moderately iodine-deficient women. Results also indicated increased risk of subfecundity and preterm delivery. Initiating iodine supplement use in pregnancy may be too late.
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2.
  • Ahlin, Kristina, et al. (författare)
  • Antecedents of cerebral palsy according to severity of motor impairment.
  • 2016
  • Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 1600-0412 .- 0001-6349. ; 95:7, s. 793-802
  • Tidskriftsartikel (refereegranskat)abstract
    • The purpose of this study was to determine whether antecedents and neuroimaging patterns vary according to the severity of motor impairment in children with cerebral palsy. Material and methods. A population-based study in which all 309 term-born children with spastic and dyskinetic cerebral palsy born between 1983 and 1994 and 618 matched controls were studied. Antecedents were retrieved from obstetric records. Information on neuroimaging was retrieved from the cerebral palsy Register of Western Sweden. Cases were grouped by severity of motor impairment: mild (walks without aids), moderate (walks with aids) or severe (dependent on wheelchair). Binary logistic regression, the Cochran-Armitage test for trends, interaction analyses and interrelationship analyses were performed. Results. Antecedents associated with mild motor impairment were antepartum (placental weight, maternal weight and antibiotic therapy) or intrapartum and postpartum adverse events (meconium-stained amniotic fluid, low Apgar score, admission to neonatal intensive care unit and neonatal encephalopathy). Antecedents associated with severe motor impairment were antepartum (congenital infection, small head circumference and brain maldevelopment) or intrapartum and postpartum (emergency cesarean section and maternal antibiotic therapy). Comparisons between mild and severe motor impairment revealed congenital infection, maldevelopment, neonatal encephalopathy and meconium aspiration syndrome significantly more often in the group with severe motor impairment (p
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3.
  • Al-Haddad, Benjamin J S, et al. (författare)
  • Long-term Risk of Neuropsychiatric Disease After Exposure to Infection In Utero.
  • 2019
  • Ingår i: JAMA psychiatry. - : American Medical Association (AMA). - 2168-6238 .- 2168-622X. ; 76:6, s. 594-602
  • Tidskriftsartikel (refereegranskat)abstract
    • The developmental origins of mental illness are incompletely understood. Although the development of autism and schizophrenia are linked to infections during fetal life, it is unknown whether more common psychiatric conditions such as depression might begin in utero.To estimate the risk of psychopathologic conditions imparted from fetal exposure to any maternal infection while hospitalized during pregnancy.A total of 1 791 520 Swedish children born between January 1, 1973, and December 31, 2014, were observed for up to 41 years using linked population-based registries. Children were excluded if they were born too late to contribute person-time, died before being at risk for the outcome, or were missing particular model data. Infection and psychiatric diagnoses were derived using codes from hospitalizations. Directed acyclic graphs were developed from a systematic literature review to determine Cox proportional hazards regression models for risk of psychopathologic conditions in the children. Results were evaluated using probabilistic and simple bias analyses. Statistical analysis was conducted from February 10 to October 17, 2018.Hospitalization during pregnancy with any maternal infection, severe maternal infection, and urinary tract infection.Inpatient diagnosis of autism, depression, bipolar disorder, or psychosis among offspring.A total of 1 791 520 Swedish-born children (48.6% females and 51.4% males) were observed from birth up to age 41 years, with a total of 32 125 813 person-years. Within the directed acyclic graph framework of assumptions, fetal exposure to any maternal infection increased the risk of an inpatient diagnosis in the child of autism (hazard ratio [HR], 1.79; 95% CI, 1.34-2.40) or depression (HR, 1.24; 95% CI, 1.08-1.42). Effect estimates for autism and depression were similar following a severe maternal infection (autism: HR, 1.81; 95% CI, 1.18-2.78; depression: HR, 1.24; 95% CI, 0.88-1.73) or urinary tract infection (autism: HR, 1.89; 95% CI, 1.23-2.90; depression: HR, 1.30; 95% CI, 1.04-1.61) and were robust to moderate unknown confounding. Within the directed acyclic graph framework of assumptions, the relationship between infection and depression was vulnerable to bias from loss to follow-up, but separate data from the Swedish Death Registry demonstrated increased risk of suicide among individuals exposed to pregnancy infection. No evidence was found for increased risk of bipolar disorder or psychosis among children exposed to infection in utero.These findings suggest that fetal exposure to a maternal infection while hospitalized increased the risk for autism and depression, but not bipolar or psychosis, during the child's life. These results emphasize the importance of avoiding infections during pregnancy, which may impart subtle fetal brain injuries contributing to development of autism and depression.
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4.
  • Alkmark, Mårten, 1973, et al. (författare)
  • Efficacy and safety of oral misoprostol versus transvaginal balloon catheter for labor induction: An observational study within the SWEdish Postterm Induction Study (SWEPIS)
  • 2021
  • Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 0001-6349 .- 1600-0412. ; 100:8, s. 1463-1477
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction Induction of labor is increasing. A common indication for induction of labor is late term and postterm pregnancy at 41 weeks or more. We aimed to evaluate if there are any differences regarding efficacy, safety, and women's childbirth experience between oral misoprostol and transvaginal balloon catheter for cervical ripening in women with a low-risk singleton pregnancy and induction of labor at 41(+0) to 42(+0 to 1) weeks of gestation. Material and methods In this observational study, based on data from the Swedish Postterm Induction Study (SWEPIS), a multicenter randomized controlled trial, a total of 1213 women with a low-risk singleton pregnancy at 41 to 42 weeks of gestation were induced with oral misoprostol (n = 744) or transvaginal balloon catheter (n = 469) at 15 Swedish delivery hospitals. The primary efficacy outcome was vaginal delivery within 24 h and primary safety outcomes were neonatal and maternal composite adverse outcomes. Secondary outcomes included time to vaginal delivery and mode of delivery. Women's childbirth experience was assessed with the Childbirth Experience Questionnaire (CEQ 2.0) and visual analog scale. We present crude and adjusted mean differences and relative risks (RR) with 95% CI. Adjustment was performed for a propensity score based on delivery hospital and baseline characteristics including Bishop score. Results Vaginal delivery within 24 h was significantly lower in the misoprostol group compared with the balloon catheter group (46.5% [346/744] versus 62.7% [294/469]; adjusted RR 0.76 95% CI 0.640.89]). Primary neonatal and maternal safety outcomes did not differ between groups (neonatal composite 3.5% [36/744] vs 3.2% [15/469]; adjusted RR 0.77 [95% CI 0.31-1.89]; maternal composite 2.3% [17/744] versus 1.9% [9/469]; adjusted RR 1.70 [95% CI 0.58-4.97]). Adjusted mean time to vaginal delivery was increased by 3.8 h (95% CI 1.3-6.2 h) in the misoprostol group. Non-operative vaginal delivery and cesarean delivery rates did not differ. Women's childbirth experience was positive overall and similar in both groups. Conclusion Induction of labor with oral misoprostol compared with a transvaginal balloon catheter was associated with a lower probability of vaginal delivery within 24 h and a longer time to vaginal delivery. However, primary safety outcomes, non-operative vaginal delivery, and women's childbirth experience were similar in both groups. Therefore, both methods can be recommended in women with low-risk postdate pregnancies.
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5.
  • Alkmark, Mårten, et al. (författare)
  • Efficacy and safety of oral misoprostol vs transvaginal balloon catheter for labor induction : An observational study within the SWEdish Postterm Induction Study (SWEPIS)
  • 2021
  • Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - : John Wiley & Sons. - 0001-6349 .- 1600-0412. ; 100:8, s. 1463-1477
  • Tidskriftsartikel (refereegranskat)abstract
    • INTRODUCTION: Induction of labor is increasing in the world. A common indication for Induction of labor is late term and postterm pregnancy at 41 gestational week and thereafter. We aimed to evaluate if there are any differences regarding efficacy, safety, and women's childbirth experience between oral misoprostol and transvaginal balloon catheter for cervical ripening in women with a low-risk singleton pregnancy and induction of labor at 41+0 to 42+0-1 gestational weeks.MATERIAL AND METHODS: In this observational study, based on data from Swedish Postterm Induction Study (SWEPIS), a multicenter randomized controlled trial, a total of 1 213 women with a low-risk singleton pregnancy at 41 to 42 gestational weeks were induced with oral misoprostol (n=744) or transvaginal balloon catheter (n=469) at 15 Swedish delivery hospitals. The primary efficacy outcome was vaginal delivery within 24 hours and primary safety outcomes were neonatal and maternal composite adverse outcomes. Secondary outcomes included time-to-vaginal delivery and mode of delivery. Women's childbirth experience was assessed with the Childbirth Experience Questionnaire (CEQ 2.0) and visual analogue scale. We present crude and adjusted mean differences and relative risks (RR) with 95% confidence interval (CI). Adjustment was performed for a propensity score based on delivery hospital and baseline characteristics including Bishop score.RESULTS: Vaginal delivery within 24 hours was significantly lower in the misoprostol compared with the balloon catheter group (46.5% [346/744] vs 62.7% [294/469]; adjusted RR 0.76 [95% CI 0.64; 0.89]). Primary neonatal and maternal safety outcomes did not differ between groups (neonatal composite 3.5% [36/744] vs 3.2% [15/469]; adjusted RR 0.77 [95% CI 0.31; 1.89]; maternal composite (2.3% [17/744] vs 1.9% [9/469]; adjusted RR 1.70 [95% CI 0.58; 4.97]). Adjusted mean time-to-vaginal delivery was increased by 3.8 hours (95% CI 1.3; 6.2) in the misoprostol group. Non-operative vaginal delivery and cesarean delivery rates did not differ. Women's childbirth experience was positive overall and similar in both groups.CONCLUSION: Induction of labor with oral misoprostol compared with a transvaginal balloon catheter was associated with a lower probability of vaginal delivery within 24 hours and a longer time-to-vaginal delivery. However, primary safety outcomes, non-operative vaginal delivery and women's childbirth experience were similar in both groups. Therefore, both methods can be recommended in women with low-risk postdate pregnancies.
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6.
  • Alkmark, Mårten, 1973, et al. (författare)
  • Induction of labour at 41 weeks of gestation versus expectant management and induction of labour at 42 weeks of gestation: a cost-effectiveness analysis
  • 2022
  • Ingår i: BJOG: An International Journal of Obstetrics and Gynaecology. - : Wiley. - 1470-0328 .- 1471-0528. ; 129:13, s. 2157-2165
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To assess the cost-effectiveness of induction of labour (IOL) at 41 weeks of gestation compared with expectant management until 42 weeks of gestation. Design: A cost-effectiveness analysis alongside the Swedish Post-term Induction Study (SWEPIS), a multicentre, randomised controlled superiority trial. Setting: Fourteen Swedish hospitals during 2016–2018. Population: Women with an uncomplicated singleton pregnancy with a fetus in cephalic position were randomised at 41 weeks of gestation to IOL or to expectant management and induction at 42 weeks of gestation. Methods: Health benefits were measured in life years and quality-adjusted life years (QALYs) for mother and child. Total cost per birth was calculated, including healthcare costs from randomisation to discharge after delivery, for mother and child. Incremental cost-effectiveness ratios (ICERs) were calculated by dividing the difference in mean cost between the trial arms by the difference in life years and QALYs, respectively. Sampling uncertainty was evaluated using non-parametric bootstrapping. Main outcome measures: The cost per gained life year and per gained QALY. Results: The differences in life years and QALYs gained were driven by the difference in perinatal mortality alone. The absolute risk reduction in mortality was 0.004 (from 6/1373 to 0/1373). Based on Swedish life tables, this gives a mean gain in discounted life years and QALYs of 0.14 and 0.12 per birth, respectively. The mean cost per birth was €4108 in the IOL group (n = 1373) and €4037 in the expectant management group (n = 1373), with a mean difference of €71 (95% CI −€232 to €379). The ICER for IOL compared with expectant management was €545 per life year gained and €623 per QALY gained. Confidence intervals were relatively wide and included the possibility that IOL had both lower costs and better health outcomes. Conclusions: Induction of labour at 41 weeks of gestation results in a better health outcome and no significant difference in costs. IOL is cost-effective compared with expectant management until 42 weeks of gestation using standard threshold values for acceptable cost per life year/QALY. Tweetable abstract: Induction of labour at 41 weeks of gestation is cost-effective compared with expectant management until 42 weeks of gestation.
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7.
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8.
  • Bacelis, Jonas, 1984, et al. (författare)
  • Literature-Informed Analysis of a Genome-Wide Association Study of Gestational Age in Norwegian Women and Children Suggests Involvement of Inflammatory Pathways
  • 2016
  • Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:8
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Five-to-eighteen percent of pregnancies worldwide end in preterm birth, which is the major cause of neonatal death and morbidity. Approximately 30% of the variation in gestational age at birth can be attributed to genetic factors. Genome-wide association studies (GWAS) have not shown robust evidence of association with genomic loci yet. We separately investigated 1921 Norwegian mothers and 1199 children from pregnancies with spontaneous onset of delivery. Individuals were further divided based on the onset of delivery: initiated by labor or prelabor rupture of membranes. Genetic association with ultrasound- dated gestational age was evaluated using three genetic models and adaptive permutations. The top-ranked loci were tested for enrichment in 12 candidate gene-sets generated by text-mining PubMed abstracts containing pregnancy-related keywords. The six GWAS did not reveal significant associations, with the most extreme empirical p = 5.1 x 10(-7). The top loci from maternal GWAS with deliveries initiated by labor showed significant enrichment in 10 PubMed gene-sets, e.g., p = 0.001 and 0.005 for keywords "uterus" and "preterm" respectively. Enrichment signals were mainly caused by infection/inflammation-related genes TLR4, NFKB1, ABCA1, MMP9. Literature-informed analysis of top loci revealed further immunity genes: IL1A, IL1B, CAMP, TREM1, TFRC, NFKBIA, MEFV, IRF8, WNT5A. Our analyses support the role of inflammatory pathways in determining pregnancy duration and provide a list of 32 candidate genes for a follow-up work. We observed that the top regions from GWAS in mothers with labor-initiated deliveries significantly more often overlap with pregnancy-related genes than would be expected by chance, suggesting that increased sample size would benefit similar studies.
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9.
  • Bacelis, Jonas, et al. (författare)
  • Uterine distention as a factor in birth timing: retrospective nationwide cohort study in Sweden.
  • 2018
  • Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 8:10
  • Tidskriftsartikel (refereegranskat)abstract
    • To determine whether uterine distention is associated with human pregnancy duration in a non-invasive observational setting.Retrospective cohort study modelling uterine distention by interaction between maternal height and uterine load.The study is based on the 1990-2013 population data from all delivery units in Sweden.Uncomplicated first pregnancies of healthy Nordic-born mothers with spontaneous onset of labour. Pregnancies were classified as twin (n=2846) or singleton (n=527 868). Singleton pregnancies were further classified as carrying a large for gestational age fetus (LGA, n=24 286) or small for gestational age fetus (SGA, n=33 780).Statistical interaction between maternal height and uterine load categories (twin vs singleton pregnancies, and LGA vs SGA singleton pregnancies), where the outcome is pregnancy duration.In all models, statistically significant interaction was found. Mothers carrying twins had 2.9 times larger positive linear effect of maternal height on gestational age than mothers carrying singletons (interaction p=5e-14). Similarly, the effect of maternal height was strongly modulated by the fetal growth rate in singleton pregnancies: the effect size of maternal height on gestational age in LGA pregnancies was 2.1 times larger than that in SGA pregnancies (interaction p<1e-11). Preterm birth OR was 1.4 when the mother was short, and 2.8 when the fetus was extremely large for its gestational age; however, when both risk factors were present together, the OR for preterm birth was larger than expected, 10.2 (interaction p<0.0005).Across all classes, maternal height was significantly associated with child's gestational age at birth. Interestingly, in short-statured women with large uterine load (twins, LGA), spontaneous delivery occurred much earlier than expected. The interaction between maternal height, uterine load size and gestational age at birth strongly suggests the effect of uterine distention imposed by fetal growth on birth timing.
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10.
  • Barman, Malin, 1983, et al. (författare)
  • Maternal dietary selenium intake is associated with increased gestational length and decreased risk of preterm delivery
  • 2020
  • Ingår i: British Journal of Nutrition. - 0007-1145 .- 1475-2662. ; 123:2, s. 209-219
  • Tidskriftsartikel (refereegranskat)abstract
    • The first positive genome-wide association study on gestational length and preterm delivery showed associations with a gene involved in the selenium metabolism. In this study we examine the associations between maternal intake of selenium and selenium status with gestational length and preterm delivery in 72,025 women with singleton live births from the population based, prospective Norwegian Mother, Father and Child Cohort Study (MoBa). A self-reported, semi-quantitativ food-frequency questionnaire answered in pregnancy week 22 was used to estimate selenium intake during the first half of pregnancy. Associations were analysed with adjusted linear and cox regressions. Selenium status was assessed in whole blood collected in gestational week 17 (n=2,637). Median dietary selenium intake was 53 (IQR: 44-62) μg/day, supplements provided additionally 50 (30-75) μg/day for supplement-users (n=23,409). Maternal dietary selenium intake was significantly associated with prolonged gestational length (β per SD=0.25, 95% CI=0.07-0.43) and decreased risk for preterm delivery (n=3,618, HR per SD=0.92, 95% CI=0.87-0.98). Neither selenium intake from supplements nor maternal blood selenium status was associated with gestational length or preterm delivery. Hence, this study showed that maternal dietary selenium intake, but not intake of selenium containing supplements, during the first half of pregnancy was significantly associated with decreased risk for preterm delivery. Further investigations, preferably in the form of a large RCT, are needed to elucidate the impact of selenium on pregnancy duration.
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