1. |
- Cordtz, Rene Lindholm, et al.
(author)
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Haematological malignancies in patients with psoriatic arthritis overall and treated with TNF inhibitors : a Nordic cohort study
- 2022
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In: RMD Open. - : BMJ Publishing Group Ltd. - 2056-5933. ; 8:2
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Journal article (peer-reviewed)abstract
- Objectives To evaluate the risk of haematological malignancies in patients with psoriatic arthritis (PsA) overall, and in relation to treatment with tumour necrosis factor inhibitors (TNFi).Methods We identified that patients with PsA starting a first TNFi from the clinical rheumatology registers (CRR) in the five Nordic countries (n=10 621) and biologics-naive PsA patients from (1) the CRR (n=18 705) and (2) the national patient registers (NPR, n=27 286, Sweden and Denmark) from 2006 through 2019. For Sweden and Denmark, general population comparators were matched 5:1 to PsA patients on birth year, year at start of follow-up and sex. By linkage to the national cancer registers in all countries, we collected information on haematological malignancies overall, and categorised into lymphoid or myeloid types. We estimated incidence rate ratios (IRRs) with 95% CIs using modified Poisson regression for TNFi-treated versus biologics-naive PsA patients and versus the general population adjusted for age, sex, calendar period and country.Results During 59 827 person-years, 40 haematological malignancies occurred among TNFi-treated patients with PsA resulting in a pooled IRR of 0.96 (0.68-1.35) versus biologics-naive PsA from CRR and an IRR of 0.84 (0.64-1.10) versus biologics-naive PsA from NPR. The IRR of haematological malignancies in PsA overall versus general population comparators was 1.35 (1.17-1.55). The estimates were largely similar for lymphoid and myeloid malignancies.Conclusions Treatment with TNFi in patients with PsA was not associated with an increased incidence of haematological malignancies. Conversely, a moderately increased underlying risk was seen in patients with PsA compared with the general population.
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2. |
- Hellgren, Karin, et al.
(author)
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Do rheumatoid arthritis and lymphoma share risk factors? : A comparison of lymphoma and cancer risks before and after diagnosis of rheumatoid arthritis
- 2010
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In: Arthritis and Rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 62:5, s. 1252-1258
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Journal article (peer-reviewed)abstract
- OBJECTIVE: Patients with rheumatoid arthritis (RA), in particular those with the most severe disease, are at increased risk of malignant lymphoma. Whether this increase is entirely consequential to the RA disease and/or its treatment or reflective of shared susceptibility to the two diseases remains unclear. To resolve this, we assessed whether patients with RA are at increased risk of lymphoma or of other cancers, already before diagnosis of RA, and if the relative risk increases with time since RA diagnosis.METHODS: 6,745 patients with incident RA (ACR criteria, symptom duration < 1 year) registered in the Swedish Early RA register from 1997 through 2006 were identified. For each patient, five general population controls were randomly matched by gender, age, marital status and residence (n=33,657). All individuals were linked to the nationwide Swedish Cancer Register 1958-2006. Relative risks (RR) of lymphoma and cancer overall before and after the diagnosis of RA were estimated using conditional logistic and Cox regression, respectively.RESULTS: Before diagnosis of RA, no increased risk of lymphoma (RR= 0.67, 95% CI 0.37-1.23) or other cancers (RR= 0.78, 95% CI 0.70-0.88) was observed. During the first ten years following diagnosis of RA, the overall RR of lymphoma was 1.75 (95 % CI 1.04-2.96).CONCLUSION: Overall, a history of cancer, lymphoma included, does not increase the risk of subsequent RA development. Shared susceptibility for RA and lymphoma may thus be of limited importance. By contrast increased lymphoma risks were observed already within the first decade following RA diagnosis.
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3. |
- Hellgren, Karin, et al.
(author)
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Lymphoma risks in patients with rheumatoid arthritis treated with biological drugs : a Swedish cohort study of risks by time, drug and lymphoma subtype
- 2021
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In: Rheumatology. - : Oxford University Press. - 1462-0324 .- 1462-0332. ; 60:2, s. 809-819
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Journal article (peer-reviewed)abstract
- OBJECTIVES: To estimate the association between biological DMARDs (bDMARDs; overall and by drug) as used in RA and the risk of malignant lymphomas including subtypes.METHODS: By linking nationwide Swedish registers we identified cohorts of patients with RA initiating treatment with a bDMARD (n = 16 392), bDMARD-naïve (n = 55 253), an age- and sex-matched general population comparator cohort (n = 229 047), and all incident lymphomas 2001-16. We used Cox regression to calculate hazard ratios (HRs) of lymphoma taking calendar period and other factors into account.RESULTS: There were 82 lymphomas among the bDMARD-treated patients with RA, crude incidence rate 76/100 000 person-years, and 310 lymphomas among the bDMARD-naïve patients with RA, crude incidence rate 90/100 000 person-years. This resulted in an adjusted HR (aHR) associated with bDMARD treatment (vs not) of 1.08 (95% CI: 0.83, 1.41). The corresponding aHR for bDMARD-treated and bDMARD-naïve vs the general population was 1.65 (95% CI: 1.31, 2.08) and 1.56 (95% CI: 1.37, 1.78) respectively. Restricting follow-up period to after 2006, the aHR of lymphoma for patients with RA starting a first bDMARD vs bDMARD-naïve was 0.69 (95% CI: 0.47, 1.00), and for bDMARD treated vs patients with RA switching from one conventional synthetic DMARDs to another, aHR was 0.46 (95% CI: 0.28, 0.73). There were no signals of different risks with any particular TNF inhibitor (TNFi) agent. We found no different lymphoma subtype pattern following bDMARD therapy.CONCLUSION: Treatment with bDMARDs, including both TNFi and non-TNFi bDMARDs, does not further increase the lymphoma risk in RA; instead, bDMARD treatment may actually reduce the excess lymphoma risk in RA.
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5. |
- Hellström, Ann, 1959, et al.
(author)
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Extreme prematurity, treated retinopathy, bronchopulmonary dysplasia and cerebral palsy are significant risk factors for ophthalmological abnormalities at 6.5years of age
- 2018
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In: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 107:5, s. 811-821
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Journal article (peer-reviewed)abstract
- Aim: This study evaluated the contributions of various prenatal and postnatal predictive factors to a documented high prevalence of ophthalmological abnormalities in children aged 6.5 years who were born extremely preterm. Methods: We carried out a prospective population-based study of all children born in Sweden at a gestational age of 22+0 to 26+6weeks based on the Extremely Preterm Infants in Sweden Study. The main outcome measures were a combined score of visual impairment, refractive errors and strabismus at 6.5years of age. Models of univariate and multivariable regression were used to analyse potential prenatal and postnatal predictive factors at different clinically relevant time-points from one minute after birth to 30months. Results: We focused on 399 known extremely preterm survivors and compared them to 300 full-term controls. Significant antecedents for ophthalmological abnormalities included prematurity per se, retinopathy of prematurity that required treatment, severe bronchopulmonary dysplasia and cerebral palsy. Severe intraventricular haemorrhage was no longer a significant risk factor when we adjusted it for the 30-month cognitive and neuromotor development outcomes. Conclusion: This time-course risk analysis model showed a changing panorama of significant risk factors for ophthalmological abnormalities in children aged 6.5years who were born extremely preterm.
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6. |
- Serenius, Fredrik, et al.
(author)
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Neurodevelopmental Outcomes Among Extremely Preterm Infants 6.5 Years After Active Perinatal Care in Sweden
- 2016
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In: Jama Pediatrics. - Chicago : American Medical Association (AMA). - 2168-6203 .- 2168-6211. ; 170:10, s. 954-963
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Journal article (peer-reviewed)abstract
- IMPORTANCE Active perinatal care increases the rate of survival of extremely preterm infants, but there are concerns that improved survival might increase the rate of disabled survivors. OBJECTIVE To determine the neurodevelopmental outcomes of a national cohort of children 6.5 years of age who had been born extremely preterm (<27 weeks' gestational age) in Sweden. DESIGN, SETTING, AND PARTICIPANTS Population-based prospective cohort study of consecutively born extremely preterm infants. All of these infants were born in Sweden during the period from April 1, 2004, to March 31, 2007. Of 707 live-born extremely preterm infants, 486 (68.7%) survived to 6.5 years of age. These children were assessed and compared with matched controls who had been born at term. Comparison estimates were adjusted for demographic differences. Assessments ended in February 2014, and analysis started thereafter. MAIN OUTCOMES AND MEASURES Cognitive ability was measured with the fourth edition of the Wechsler Intelligence Scale for Children (WISC-IV), and the mean (SD) scores of the children who had been born extremely preterm were compared with those of the controls. Clinical examinations and parental questionnaires were used for diagnosis of cerebral palsy, hearing and vision impairments, and cognition for the children who were not assessed with the WISC-IV. RESULTS Of 486 eligible infants who were born extremely preterm, 441 (90.7%) were assessed at 6.5 years of age (59 by medical record review only) alongside 371 controls. The adjusted mean (SD) full-scale WISC-IV score was 14.2 (95% CI, 12.1-16.3) points lower for children who had been born extremely preterm than for controls. Cognitive disability was moderate for 18.8% of extremely preterm children and 2.2% of controls (P < .001), and it was severe for 11.1% of extremely preterm children and 0.3% of controls (P < .001). Cerebral palsy was observed in 9.5% of extremely preterm children and 0.0% of controls (P < .001), blindness was observed in 2.0% of extremely preterm children and 0.0% of controls (P < .001), and hearing impairment was observed in 2.1% of extremely preterm children and 0.5% of controls (P = .07). Overall, 36.1%(95% CI, 31.7%-40.6%) of extremely preterm children had no disability, 30.4%(95% CI 26.3%-34.8%) had mild disability, 20.2%(95% CI, 16.6%-24.2%) had moderate disability, and 13.4%(95% CI, 10.5%-16.9%) had severe disability. For extremely preterm children, moderate or severe overall disability decreased with gestational age at birth (adjusted odds ratio per week, 0.65 [95% CI, 0.54-0.79]; P < .001) and increased from 26.6% to 33.5%(P = .01) for children assessed both at 2.5 and 6.5 years. CONCLUSIONS AND RELEVANCE Of the 441 extremely preterm infants who had received active perinatal care, 293 (66.4%) had no or mild disability at 6.5 years; of the 371 controls, 11 (3.0%) had moderate or severe disability. Disability rates at 6.5 years increased relative to the rates at 2.5 years. Results are relevant for health care professionals and planners, and for clinicians counseling families facing extremely preterm births.
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7. |
- Axfors, Cathrine, et al.
(author)
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Neuroticism is associated with higher antenatal care utilization in obstetric low-risk women
- 2019
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In: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 0001-6349 .- 1600-0412. ; 98:4, s. 470-478
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Journal article (peer-reviewed)abstract
- IntroductionElevated neuroticism is associated with higher health care utilization in the general population. This study aimed to investigate the association between neuroticism and the use of publicly financed antenatal care in obstetric low‐risk women, taking predisposing and need factors for health care utilization into consideration.Material and methodsParticipants comprised 1052 obstetric low‐risk women (no chronic diseases or adverse pregnancy conditions) included in several obstetrics/gynecology studies in Uppsala, Sweden. Neuroticism was self‐rated on the Swedish universities Scales of Personality. Medical records of their first subsequent pregnancy were scanned for antenatal care use. Associations between antenatal care use and neuroticism were analyzed with logistic regression (binary outcomes) or negative binomial regression (count outcomes) comparing the 75th and 25th neuroticism percentiles. Depending on the Akaike information criterion the exposure was modeled as either linear or with restricted cubic splines. Analyses were adjusted for predisposing (sociodemographic and parity) and need factors (body mass index and psychiatric morbidity).ResultsAfter adjustment, women with higher neuroticism had more fetal ultrasounds (incidence rate ratio = 1.09, 95% confidence interval (CI) 1.02‐1.16), more emergency visits to an obstetrician/gynecologist (incidence rate ratio = 1.22, 95% CI 1.03‐1.45) and were more likely to visit a fear‐of‐childbirth clinic (odds ratio = 2.71, 95% CI 1.71‐4.29). Moreover, they more often consulted midwives in specialized antenatal care facilities (significant J‐shaped association).ConclusionsNeuroticism was associated with higher utilization of publicly financed antenatal care in obstetric low‐risk women, even after adjusting for predisposing and need factors. Future studies should address the benefits of interventions as a complement to routine antenatal care programs to reduce subclinical anxiety.
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8. |
- Bolk, Jenny, et al.
(author)
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National population-based cohort study found that visual-motor integration was commonly affected in extremely preterm born children at six-and-a-half years
- 2018
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In: Acta Paediatrica. - : WILEY. - 0803-5253 .- 1651-2227. ; 107:5, s. 831-837
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Journal article (peer-reviewed)abstract
- Aim: This study aimed to explain the relationship between visual-motor integration (VMI) abilities and extremely preterm (EPT) birth, by exploring the influence of perinatal variables, cognition, manual dexterity and ophthalmological outcomes. Methods: This was part of the population-based national Extremely Preterm Infant Study in Sweden (EXPRESS) study. We studied 355 children, born at a gestational age of <27 weeks from April 2004 to March 2007, and 364 term-born controls. At six-and-a-half years of age, we assessed VMI, cognitive function, motor skills and vision. VMI impairment was classified as <-1 standard deviation (SD). Results: The mean (SD) VMI score was 87 (+/- 12) in preterm children compared to 98 (+/- 11) in controls (p < 0.001). VMI impairment was present in 55% of preterm infants and in 78% of children born at 22-23 weeks. Male sex and postnatal steroids showed a weak association with poorer visual-motor performance, whereas low manual dexterity and cognitive function showed a stronger association. Conclusion: Poor VMI performance was common in this EXPRESS cohort of children born EPT. Its strong association to cognition and manual dexterity confirms that all of these factors need to be taken into account when evaluating risks in preterm born children.
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9. |
- Broms, Gabriella, et al.
(author)
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Anti-TNF treatment during pregnancy and birth outcomes : Apopulation-based study from Denmark, Finland, and Sweden
- 2020
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In: Pharmacoepidemiology and Drug Safety. - : Wiley. - 1053-8569 .- 1099-1557. ; 29:3, s. 316-327
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Journal article (peer-reviewed)abstract
- Purpose: To study the risk of preterm birth, caesarean section, and small for gestational age after anti-tumor necrosis factor agent treatment (anti-TNF) in pregnancy.Methods: Population-based study including women with inflammatory bowel disease, rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and psoriasis, and their infants born 2006 to 2013 from the national health registers in Denmark, Finland, and Sweden. Women treated with anti-TNF were compared with women with nonbiologic systemic treatment. Adalimumab, etanercept, and infliximab were compared pairwise. Continuation of treatment in early pregnancy was compared with discontinuation. Odds ratios with 95% confidence intervals were calculated in logistic regression models adjusted for country and maternal characteristics.Results: Among 1 633 909 births, 1027 infants were to women treated with anti-TNF and 9399 to women with nonbiologic systemic treatment. Compared with non-biologic systemic treatment, women with anti-TNF treatment had a higher risk of preterm birth, odds ratio 1.61 (1.29-2.02) and caesarean section, 1.57 (1.35-1.82). The odds ratio for small for gestational age was 1.36 (0.96-1.92). In pairwise comparisons, infliximab was associated with a higher risk of severely small for gestational age for inflammatory joint and skin diseases but not for inflammatory bowel disease. Discontinuation of anti-TNF had opposite effects on preterm birth for inflammatory bowel disease and inflammatory joint and skin diseases.Conclusions: Anti-TNF agents were associated with increased risks of preterm birth, caesarean section, and small for gestational age. However, the diverse findings across disease groups may indicate an association related to the underlying disease activity, rather than to agent-specific effects.
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11. |
- Brännholm Syrjälä, Maria, et al.
(author)
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Health effects of reduced occupational sedentary behaviour in type 2 diabetes using a mobile health intervention : a study protocol for a 12-month randomized controlled trial—the ROSEBUD study
- 2022
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In: Trials. - : BioMed Central. - 1745-6215. ; 23:1
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Journal article (peer-reviewed)abstract
- Background: Short-term trials conducted in adults with type 2 diabetes mellitus (T2DM) showed that reducing sedentary behaviour by performing regular short bouts of light-intensity physical activity enhances health. Moreover, support for reducing sedentary behaviour may be provided at a low cost via mobile health technology (mHealth). There are a wide range of mHealth solutions available including SMS text message reminders and activity trackers that monitor the physical activity level and notify the user of prolonged sitting periods. The aim of this study is to evaluate the effects of a mHealth intervention on sedentary behaviour and physical activity and the associated changes in health in adults with T2DM.Methods: A dual-arm, 12-month, randomized controlled trial (RCT) will be conducted within a nationwide Swedish collaboration for diabetes research in primary health care. Individuals with T2DM (n = 142) and mainly sedentary work will be recruited across primary health care centres in five regions in Sweden. Participants will be randomized (1:1) into two groups. A mHealth intervention group who will receive an activity tracker wristband (Garmin Vivofit4), regular SMS text message reminders, and counselling with a diabetes specialist nurse, or a comparator group who will receive counselling with a diabetes specialist nurse only. The primary outcomes are device-measured total sitting time and total number of steps (activPAL3). The secondary outcomes are fatigue, health-related quality of life and musculoskeletal problems (self-reported questionnaires), number of sick leave days (diaries), diabetes medications (clinical record review) and cardiometabolic biomarkers including waist circumference, mean blood pressure, HbA1c, HDL-cholesterol and triglycerides.Discussion: Successful interventions to increase physical activity among those with T2DM have been costly and long-term effectiveness remains uncertain. The use of mHealth technologies such as activity trackers and SMS text reminders may increase awareness of prolonged sedentary behaviour and encourage increase in regular physical activity. mHealth may, therefore, provide a valuable and novel tool to improve health outcomes and clinical management in those with T2DM. This 12-month RCT will evaluate longer-term effects of a mHealth intervention suitable for real-world primary health care settings.
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12. |
- Bröms, Gabriella, et al.
(author)
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Paediatric infections in the first 3 years of life after maternal anti-TNF treatment during pregnancy
- 2020
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In: Alimentary Pharmacology and Therapeutics. - : John Wiley & Sons. - 0269-2813 .- 1365-2036. ; 52:5, s. 843-854
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Journal article (peer-reviewed)abstract
- Background: Most anti‐tumour necrosis factor (anti‐TNF) agents are transferred across the placenta and may increase paediatric susceptibility to infections.Aims: To assess the risk of paediatric infections after maternal anti‐TNF treatment.Methods: Population‐based cohort study in Denmark, Finland and Sweden 2006‐2013 in which 1027 children born to women with rheumatoid arthritis, psoriasis, psoriatic arthritis, ankylosing spondylitis or inflammatory bowel disease, treated with anti‐TNF, and 9346 children to women with nonbiologic systemic treatment, were compared to 1 617 886 children of the general population. Children were followed for 3 years.Results: Adjusted by maternal age, parity, smoking, body mass index, country and calendar year, the incidence rate ratios with 95% confidence interval (CI) for hospital admissions for infection in the first year were 1.43 (1.23‐1.67) for anti‐TNF and 1.14 (1.07‐1.21) for non‐biologic systemic treatment, and 1.29 (1.11‐1.50) and 1.09 (1.02‐1.15), respectively, when additionally adjusting for adverse birth outcomes. There was a slight increase in antibiotic prescriptions in the second year for anti‐TNF, 1.19 (1.11‐1.29), and for non‐biologic systemic treatment, 1.10 (1.07‐1.13). There was no difference among anti‐TNF agents, treatment in the third trimester, or between mono/combination therapy with non‐biologic systemic treatment.Conclusions: Both anti‐TNF and non‐biologic systemic treatment were associated with an increased risk of paediatric infections. However, reassuringly, the increased risks were present regardless of treatment in the third trimester, with combination of treatments, and were not persistent across the first 3 years of life. Our findings may indicate a true risk, but could also be due to unadjusted confounding by disease severity and healthcare‐seeking behaviour. This may in turn shift the risk‐benefit equation towards continuation of treatment even in the third trimester.
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14. |
- Collen, Anna-Clara, 1970, et al.
(author)
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Cardiovascular and metabolic characteristics 40 years after hypertensive pregnancies: a long-term follow-up study of mothers.
- 2013
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In: Journal of hypertension. - 1473-5598. ; 31:4, s. 758-765
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Journal article (peer-reviewed)abstract
- OBJECTIVES:: Maternal cardiovascular morbidity is increased after hypertensive pregnancies (HTP). The pathways from complicated pregnancies to future cardiovascular disease are complex. The aim of the present study was to test the hypothesis that different cardiovascular mechanisms are changed in women who experienced HTP four decades earlier in comparison to women with normotensive pregnancies. METHODS:: One hundred and five women (50 with hypertensive and 55 with normal pregnancies) were examined with anthropometric measurements; office blood pressure, ambulatory blood pressure and central blood pressure, pulse wave velocity, augmentation index, intimal-media thickness, echocardiography and laboratory measurements. In addition another 204 women were followed-up by a questionnaire regarding their pregnancy 40 years ago, as well as their present health status and medications. RESULTS:: Women with HTP had more often diagnosed hypertension when compared with women with normal pregnancies (50 vs. 31%, respectively; P=0.046), but the groups did not differ in any blood pressure levels. HTP were associated with higher pulse wave velocity (8.8m/s vs. 7.8m/s, P=0.021), and higher levels of P-glucose (5.7mmol/l vs. 5.2mmol/l, P=0.022), P-HbA1c (4.4% vs. 4.2%, P=0.010) and noradrenaline (2.45mmol/l vs. 2.11mmol/l, P=0.040) when compared with normotensive pregnancies. Women followed up with a questionnaire reported deteriorated cardiovascular health compared to women attending the clinical investigations of the study. CONCLUSION:: HTP are associated with impairment in vascular function and metabolic status 40 years postpartum despite well controlled blood pressure levels.
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15. |
- Collen, Anna-Clara, 1970, et al.
(author)
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Cardiovascular response to stress and perceived stress is not altered 40 years after hypertensive pregnancies
- 2015
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In: Hypertension in Pregnancy. - : Informa UK Limited. - 1064-1955 .- 1525-6065. ; 34:1, s. 116-124
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Journal article (peer-reviewed)abstract
- Objective: Women experiencing hypertensive pregnancies have an increased risk for cardiovascular disease. Whether stress increase the risk is unknown. The objective was to test if cardiovascular response to stress and/or perceived stress differed in relation to blood pressure status during pregnancy 40 years earlier. Methods: Cardiovascular response was examined with mental stress test, and perceived stress was evaluated with a questionnaire in 105 women. Results: Resting heart rate was higher, and pulse reactivity was lower in women with previous hypertensive pregnancies. Neither blood pressure nor perceived stress differed. Conclusion: Response to physical or psychological stress is not affected many years after pregnancy.
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16. |
- Cuapio, Angelica, et al.
(author)
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NK cell frequencies, function and correlates to vaccine outcome in BNT162b2 mRNA anti-SARS-CoV-2 vaccinated healthy and immunocompromised individuals
- 2022
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In: Molecular Medicine. - : BioMed Central (BMC). - 1076-1551 .- 1528-3658. ; 28:1
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Journal article (peer-reviewed)abstract
- Adaptive immune responses have been studied extensively in the course of mRNA vaccination against COVID-19. Considerably fewer studies have assessed the effects on innate immune cells. Here, we characterized NK cells in healthy individuals and immunocompromised patients in the course of an anti-SARS-CoV-2 BNT162b2 mRNA prospective, open-label clinical vaccine trial. See trial registration description in notes. Results revealed preserved NK cell numbers, frequencies, subsets, phenotypes, and function as assessed through consecutive peripheral blood samplings at 0, 10, 21, and 35 days following vaccination. A positive correlation was observed between the frequency of NKG2C+ NK cells at baseline (Day 0) and anti-SARS-CoV-2 Ab titers following BNT162b2 mRNA vaccination at Day 35. The present results provide basic insights in regards to NK cells in the context of mRNA vaccination, and have relevance for future mRNA-based vaccinations against COVID-19, other viral infections, and cancer.Trial registration: The current study is based on clinical material from the COVAXID open-label, non-randomized prospective clinical trial registered at EudraCT and clinicaltrials.gov (no. 2021–000175-37). Description: https://clinicaltrials.gov/ct2/show/NCT04780659?term=2021-000175-37&draw=2&rank=1.
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17. |
- Eckerdal, Patricia, 1972-, et al.
(author)
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Delineating the Association between Heavy Postpartum Haemorrhage and Postpartum Depression
- 2016
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:1
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Journal article (peer-reviewed)abstract
- ObjectivesTo explore the association between postpartum haemorrhage (PPH) and postpartum depression (PPD), taking into account the role of postpartum anaemia, delivery experience and psychiatric history.MethodsA 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.ResultsThere 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.ConclusionThis study proposes important roles for postpartum anaemia, negative experience of delivery and mood during pregnancy in explaining the development of depressive symptoms after PPH.
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18. |
- Ekman-Ordeberg, Gunvor, et al.
(author)
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Tafoxiparin, a novel drug candidate for cervical ripening and labor augmentation: results from 2 randomized, placebo-controlled studies
- 2024
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In: American Journal of Obstetrics and Gynecology. - 0002-9378 .- 1097-6868. ; 230:3
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Research review (peer-reviewed)abstract
- Background: Slow progression of labor is a common obstetrical problem with multiple associated complications. Tafoxiparin is a depolymerized form of heparin with a molecular structure that eliminates the anticoagulant effects of heparin. We report on 2 phase II clinical studies of tafoxiparin in primiparas. Study 1 was an exploratory, first-in-pregnant-women study and study 2 was a dose-finding study. Objective: Study 1 was performed to explore the effects on labor time of subcutaneous administration of tafoxiparin before onset of labor. Study 2 was performed to test the hypothesis that intravenous treatment with tafoxiparin reduces the risk for prolonged labor after spontaneous labor onset in situations requiring oxytocin stimulation because of dystocia. Study Design: Both studies were randomized, double-blind, and placebo-controlled. Participants were healthy, nulliparous females aged 18 to 45 years with a normal singleton pregnancy and gestational age confirmed by ultrasound. The primary endpoints were time from onset of established labor (cervical dilation of 4 cm) until delivery (study 1) and time from start of study treatment infusion until delivery (study 2). In study 1, patients at 38 to 40 weeks of gestation received 60 mg tafoxiparin or placebo daily as 0.4 mL subcutaneous injections until labor onset (maximum 28 days). In study 2, patients experiencing slow progression of labor, a prolonged latent phase, or labor arrest received a placebo or 1 of 3 short-term tafoxiparin regimens (initial bolus 7, 21, or 35 mg followed by continuous infusion at 5, 15, or 25 mg/hour until delivery; maximum duration, 36 hours) in conjunction with oxytocin. Results: The number of participants randomized in study 1 was 263, and 361 were randomized in study 2. There were no statistically significant differences in the primary endpoints between those receiving tafoxiparin and those receiving the placebo in both studies. However, in study 1, the risk for having a labor time exceeding 12 hours was significantly reduced by tafoxiparin (tafoxiparin 6/114 [5%] vs placebo 18/101 [18%]; P=.0045). Post hoc analyses showed that women who underwent labor induction had a median (range) labor time of 4.44 (1.2–8.5) hours with tafoxiparin and 7.03 (1.5–14.3) hours with the placebo (P=.0041) and that co-administration of tafoxiparin potentiates the effect of oxytocin and facilitates a shorter labor time among women with a labor time exceeding 6 to 8 hours (P=.016). Among women induced into labor, tafoxiparin had a positive effect on cervical ripening in 11 of 13 cases (85%) compared with 3 of 13 participants (23%) who received the placebo (P=.004). For women requiring oxytocin because of slow progression of labor, the corresponding results were 34 of 51 participants (66%) vs 16 of 40 participants (40%) (P=.004). In study 2, tafoxiparin had no positive effects on the secondary endpoints when compared with the placebo. Except for injection-site reactions in study 1, adverse events were no more common for tafoxiparin than for the placebo among either mothers or infants. There were few serious or treatment-related adverse events. Conclusion: Subcutaneous treatment with tafoxiparin before labor onset (study 1) may be effective in reducing the labor time among women undergoing labor induction and among those requiring oxytocin for slow progression of labor. Moreover, tafoxiparin may have a positive effect on cervical ripening. Short-term, intravenous treatment with tafoxiparin as an adjunct to oxytocin in patients with labor arrest (study 2) did not affect labor time or other endpoints. Both studies suggest that tafoxiparin has a favorable safety profile in mothers and their infants.
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19. |
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Ethnicity and Social Divisions : Contemporary Research in Sociology
- 2008
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Editorial collection (other academic/artistic)abstract
- The anthology "Ethnicity and Social Divisions: Contemporary Research in Sociology" is a collection of studies presented at the annual Aage Sorensen Memorial Conferences in 2006 and 2007. The volume reflects a number of important tendencies in contemporary social research: the increasing interest in questions that concern ethnicity and immigration on the one hand, the remaining centrality of social stratification and class analysis on the other hand, and the intersection between these fields. Eight young sociologists, all PhD Candidates at the universities of Harvard, Oxford or Stockholm at the time they wrote their contributions, participate in this volume. Representing a new generation of social scientists, they have conducted empirical research on social inequality related to class and ethnicity from different perspectives.
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20. |
- Fecchio, Alan, et al.
(author)
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Global drivers of avian haemosporidian infections vary across zoogeographical regions
- 2021
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In: Global Ecology and Biogeography. - : Wiley. - 1466-822X .- 1466-8238. ; 30:12, s. 2393-2406
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Journal article (peer-reviewed)abstract
- Aim: Macroecological analyses provide valuable insights into factors that influence how parasites are distributed across space and among hosts. Amid large uncertainties that arise when generalizing from local and regional findings, hierarchical approaches applied to global datasets are required to determine whether drivers of parasite infection patterns vary across scales. We assessed global patterns of haemosporidian infections across a broad diversity of avian host clades and zoogeographical realms to depict hotspots of prevalence and to identify possible underlying drivers. Location: Global. Time period: 1994–2019. Major taxa studied: Avian haemosporidian parasites (genera Plasmodium, Haemoproteus, Leucocytozoon and Parahaemoproteus). Methods: We amalgamated infection data from 53,669 individual birds representing 2,445 species world-wide. Spatio-phylogenetic hierarchical Bayesian models were built to disentangle potential landscape, climatic and biotic drivers of infection probability while accounting for spatial context and avian host phylogenetic relationships. Results: Idiosyncratic responses of the three most common haemosporidian genera to climate, habitat, host relatedness and host ecological traits indicated marked variation in host infection rates from local to global scales. Notably, host ecological drivers, such as migration distance for Plasmodium and Parahaemoproteus, exhibited predominantly varying or even opposite effects on infection rates across regions, whereas climatic effects on infection rates were more consistent across realms. Moreover, infections in some low-prevalence realms were disproportionately concentrated in a few local hotspots, suggesting that regional-scale variation in habitat and microclimate might influence transmission, in addition to global drivers. Main conclusions: Our hierarchical global analysis supports regional-scale findings showing the synergistic effects of landscape, climate and host ecological traits on parasite transmission for a cosmopolitan and diverse group of avian parasites. Our results underscore the need to account for such interactions, in addition to possible variation in drivers across regions, to produce the robust inference required to predict changes in infection risk under future scenarios.
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21. |
- Gao, Yu, et al.
(author)
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Immunodeficiency syndromes differentially impact the functional profile of SARS-CoV-2-specific T cells elicited by mRNA vaccination
- 2022
-
In: Immunity. - : Elsevier. - 1074-7613 .- 1097-4180. ; 55:9, s. 1732-1746.e5
-
Journal article (peer-reviewed)abstract
- Many immunocompromised patients mount suboptimal humoral immunity after SARS-CoV-2 mRNA vaccination. Here, we assessed the single-cell profile of SARS-CoV-2-specific T cells post-mRNA vaccination in healthy individuals and patients with various forms of immunodeficiencies. Impaired vaccine-induced cell-mediated immunity was observed in many immunocompromised patients, particularly in solid-organ transplant and chronic lymphocytic leukemia patients. Notably, individuals with an inherited lack of mature B cells, i.e., X-linked agammaglobulinemia (XLA) displayed highly functional spike-specific T cell responses. Single-cell RNA-sequencing further revealed that mRNA vaccination induced a broad functional spectrum of spike-specific CD4+ and CD8+ T cells in healthy individuals and patients with XLA. These responses were founded on polyclonal repertoires of CD4+ T cells and robust expansions of oligoclonal effector-memory CD45RA+ CD8+ T cells with stem-like characteristics. Collectively, our data provide the functional continuum of SARS-CoV-2-specific T cell responses post-mRNA vaccination, highlighting that cell-mediated immunity is of variable functional quality across immunodeficiency syndromes.
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22. |
- Hannerfors, Anna-Karin, et al.
(author)
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Treatment with serotonin reuptake inhibitors during pregnancy is associated with elevated corticotropin-releasing hormone levels
- 2015
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In: Psychoneuroendocrinology. - : Elsevier BV. - 0306-4530 .- 1873-3360. ; 58, s. 104-113
-
Journal article (peer-reviewed)abstract
- Treatment with serotonin reuptake inhibitors (SSRI) has been associated with an increased risk of preterm birth, but causality remains unclear. While placental CRH production is correlated with gestational length and preterm birth, it has been difficult to establish if psychological stress or mental health problems are associated with increased CRH levels. This study compared second trimester CRH serum concentrations in pregnant women on SSRI treatment (n=207) with untreated depressed women (n=56) and controls (n=609). A secondary aim was to investigate the combined effect of SSRI treatment and CRH levels on gestational length and risk for preterm birth. Women on SSRI treatment had significantly higher second trimester CRH levels than controls, and untreated depressed women. CRH levels and SSRI treatment were independently associated with shorter gestational length. The combined effect of SSRI treatment and high CRH levels yielded the highest risk estimate for preterm birth. SSRI treatment during pregnancy is associated with increased CRH levels. However, the elevated risk for preterm birth in SSRI users appear not to be mediated by increased placental CRH production, instead CRH appear as an independent risk factor for shorter gestational length and preterm birth.
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23. |
- Helldén, Anders, et al.
(author)
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Fluconazole-induced intoxication with phenytoin in a patient with ultra-high activity of CYP2C9
- 2010
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In: European Journal of Clinical Pharmacology. - : Springer Science and Business Media LLC. - 0031-6970 .- 1432-1041. ; 66:8, s. 791-5
-
Journal article (peer-reviewed)abstract
- PURPOSE: The cytochrome P450 enzyme CYP2C9 metabolizes several important drugs, such as warfarin and oral antidiabetic drugs. The enzyme is polymorphic, and all known alleles, for example, CYP2C9*2 and*3, give decreased activity. Ultra-high activity of the enzyme has not yet been reported.METHODS: We present a patient with Behçet's disease who required treatment with high doses of phenytoin. When fluconazole, a potent inhibitor of CYP2C9, was added to the treatment regimen, the patient developed ataxia, tremor, fatigue, slurred speech and somnolence, indicating phenytoin intoxication. On suspicion of ultra-high activity of CYP2C9, a phenotyping test for CYP2C9 with losartan was performed.RESULTS: The patient was shown to have a higher activity of CYP2C9 than any of the 190 healthy Swedish Caucasians used as controls.CONCLUSIONS: Our finding of an ultrarapid metabolism of losartan and phenytoin may apply to other CYP2C9 substrates, where inhibition of CYP2C9 may cause severe adverse drug reactions.
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24. |
- Hellgren, Fredrika, et al.
(author)
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Modulation of innate immune response to mRNA vaccination after SARS-CoV-2 infection or sequential vaccination in humans
- 2024
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In: JCI Insight. - : American Society for Clinical Investigation (ASCI). - 2379-3708. ; 9:9
-
Journal article (peer-reviewed)abstract
- mRNA vaccines are likely to become widely used for the prevention of infectious diseases in the future. Nevertheless, a notable gap exists in mechanistic data, particularly concerning the potential effects of sequential mRNA immunization or preexisting immunity on the early innate immune response triggered by vaccination. In this study, healthy adults, with or without documented prior SARS-CoV-2 infection, were vaccinated with the BNT162b2/Comirnaty mRNA vaccine. Prior infection conferred significantly stronger induction of proinflammatory and type I IFN-related gene signatures, serum cytokines, and monocyte expansion after the prime vaccination. The response to the second vaccination further increased the magnitude of the early innate response in both study groups. The third vaccination did not further increase vaccine-induced inflammation. In vitro stimulation of PBMCs with TLR ligands showed no difference in cytokine responses between groups, or before or after prime vaccination, indicating absence of a trained immunity effect. We observed that levels of preexisting antigen-specific CD4 T cells, antibody, and memory B cells correlated with elements of the early innate response to the first vaccination. Our data thereby indicate that preexisting memory formed by infection may augment the innate immune activation induced by mRNA vaccines.
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25. |
- Hellgren, Gunnel, 1961, et al.
(author)
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Decreased Platelet Counts and Serum Levels of VEGF-A, PDGF-BB, and BDNF in Extremely Preterm Infants Developing Severe ROP
- 2021
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In: Neonatology. - : S. Karger AG. - 1661-7800 .- 1661-7819. ; 118, s. 18-27
-
Journal article (peer-reviewed)abstract
- Introduction: Thrombocytopenia has been identified as an independent risk factor for retinopathy of prematurity (ROP), although underlying mechanisms are unknown. In this study, the association of platelet count and serum platelet-derived factors with ROP was investigated. Methods: Data for 78 infants born at gestational age (GA) <28 weeks were included. Infants were classified as having no/mild ROP or severe ROP. Serum levels of vascular endothelial growth factor A, platelet-derived growth factor BB, and brain-derived neurotrophic factor were measured in serum samples collected from birth until postmenstrual age (PMA) 40 weeks. Platelet counts were obtained from samples taken for clinical indication. Results: Postnatal platelet counts and serum concentrations of the 3 growth factors followed the same postnatal pattern, with lower levels in infants developing severe ROP at PMA 32 and 36 weeks (p < 0.05-0.001). With adjustment for GA, low platelet counts and low serum concentrations of all 3 factors at PMA 32 weeks were significantly associated with severe ROP. Serum concentrations of all 3 factors also strongly correlated with platelet count (p < 0.001). Conclusion: In this article, we show that ROP, platelet counts, and specific pro-angiogenic factors correlate. These data suggest that platelet-released factors might be involved in the regulation of retinal and systemic angiogenesis after extremely preterm birth. Further investigations are needed.
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26. |
- Hellgren, Karin
(author)
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Chronic inflammation, anti-inflammatory treatment and risk of malignant lymphomas
- 2013
-
Doctoral thesis (other academic/artistic)abstract
- The aim of this thesis was to investigate the link between malignant lymphomas and chronic inflammation, in particular the associations between inflammatory activity, immune-modulatory treatment and risk of lymphoma development. To address this aim, we used Swedish population-based registers, mandatory cancer reporting and nation-wide clinical registers including the Swedish Rheumatology Register (SRQ). In study I we investigated whether patients with rheumatoid arthritis (RA) are at increased risk of lymphoma or cancer overall before clinical onset of RA, and if this risk increases with time since RA diagnosis. A cohort of 6,745 incident RA patients (1997-2006) was identified using data from the SRQ. Each cohort member was matched to five population comparator subjects. Relative risks of lymphoma and cancer overall before and after diagnosis of RA were estimated. We observed no increased risks before diagnosis of RA whereas during the first ten years following diagnosis, the lymphoma risk was almost doubled with a non-significant trend of increasing risks with longer RA disease duration. In study II with a larger study population and with longer follow-up, we set out to assess whether the lymphoma risk remains elevated in RA patients diagnosed in the last few years and to explore potential risk predictors in relation to disease characteristics and therapy, focusing on the first year following RA diagnosis. Through SRQ, a cohort of 10,367 incident RA patients (1997-2010) was assembled. Each patient was matched to five population comparator subjects. The risk of lymphoma in recently diagnosed RA patients remained increased to the same magnitude as that reported from historical RA cohorts without any change in risk in recent years. The results indicated that inflammatory activity during the 1st year following RA diagnosis correlated with higher lymphoma risk, whereas oral glucocorticoids were associated with a reduced risk. Exposure to tumor necrosis factor inhibitor (TNFi) during the study period was not associated with increased lymphoma risk. Through histopathological classification, we further noted an increased proportion of Hodgkin lymphoma and diffuse large B-cell lymphoma and a decreased proportion of chronic lymphocytic leukemia in RA patients compared with the general population. In study III the relationship between treatment with glucocorticoids and lymphoma risk in RA patients was investigated in a case-control study. From a nationwide cohort of 74,651 prevalent RA patients 1964-1994, 378 RA patients with lymphoma and 378 matched RA controls were identified. Different aspects of glucocorticoid treatment were abstracted from medical records. Treatment with glucocorticoids, oral as well as intra-articular, was associated with a reduced lymphoma risk. In study IV the underlying risks of lymphoma in patients with ankylosing spondylitis (AS) and psoriatic arthritis (PsA) were investigated, including risks in relation to disease characteristics and treatment. Nationwide prevalent cohorts of AS (n=8,707) and PsA (n=19,283) 2001-2010 were assembled. Each cohort member was matched to five population comparator subjects. On average, we observed no increased risks of lymphoma in AS or in PsA, although there was a risk increase in PsA patients treated with methotrexate and/or sulfasalazine. Based on small numbers there was no evidence of increased lymphoma incidence following therapy with TNFi in AS or in PsA patients.
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27. |
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28. |
- Hellgren, Karin, et al.
(author)
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Rheumatoid arthritis, treatment with corticosteroids, and risk of malignant lymphomas : results from a case-control study
- 2010
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In: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 69:4, s. 654-659
-
Journal article (peer-reviewed)abstract
- OBJECTIVE:Benefits and risks of corticosteroid treatment in rheumatoid arthritis (RA) are debated. Patients with RA are at increased risk of malignant lymphomas. In a large case-control study of risk factors for lymphoma in RA, we recently reported that steroid treatment was associated with decreased lymphoma risk. This study sought to further assess the nature of this association.METHODS:In a cohort of 74,651 patients with RA, we identified 378 cases with lymphoma and 378 matched RA controls, and abstracted information on inflammatory activity and different aspects of steroid treatment (duration, therapeutic strategy and mode of administration) from their medical records. Lymphomas were reclassified (WHO classification) and examined for Epstein-Barr virus. Relative risks were assessed as adjusted odds ratios (OR) through conditional logistic regression.RESULTS:A total duration of oral steroid treatment less than two years was not associated with lymphoma risk (OR=0.87; 95% confidence interval [CI] 0.51-1.5), whereas total treatment longer than two years was associated with a lower lymphoma risk (OR= 0.43; 95% CI 0.26-0.72). RA duration at the initiation of oral steroids did not affect lymphoma risk. Intra-articular steroids were associated with a reduced lymphoma risk, but only when used as swift flare therapy (OR= 0.22; 95% CI 0.13-0.37). Analyses by lymphoma subtype showed a reduced risk of diffuse large B-cell lymphoma (crude OR=0.59; 95% CI 0.37-0.94).CONCLUSION:In this RA population, use of steroids was associated with reduced lymphoma risk. Whether this association is a generic effect of steroids or specific to the studied population remains unknown.
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29. |
- Hellström, Ann, 1959, et al.
(author)
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Docosahexaenoic Acid and Arachidonic Acid Levels Are Associated with Early Systemic Inflammation in Extremely Preterm Infants
- 2020
-
In: Nutrients. - : MDPI AG. - 2072-6643. ; 12:7
-
Journal article (peer-reviewed)abstract
- Fetal and early postnatal inflammation have been associated with increased morbidity in extremely preterm infants. This study aimed to demonstrate if postpartum levels of docosahexaenoic acid (DHA) and arachidonic acid (AA) were associated with early inflammation. In a cohort of 90 extremely preterm infants, DHA and AA in cord blood, on the first postnatal day and on postnatal day 7 were examined in relation to early systemic inflammation, defined as elevated C-reactive protein (CRP) and/or interleukin-6 (IL-6) within 72 h from birth, with or without positive blood culture. Median serum level of DHA was 0.5 mol% (95% CI (confidence interval) 0.2-0.9,P= 0.006) lower than the first postnatal day in infants with early systemic inflammation, compared to infants without signs of inflammation, whereas levels of AA were not statistically different between infants with and without signs of inflammation. In cord blood, lower serum levels of both DHA (correlation coefficient -0.40;P= 0.010) and AA (correlation coefficient -0.54;p< 0.001) correlated with higher levels of IL-6. Levels of DHA or AA did not differ between infants with and without histological signs of chorioamnionitis or fetal inflammation. In conclusion, serum levels of DHA at birth were associated with the inflammatory response during the early postnatal period in extremely preterm infants.
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30. |
- Hellström, Ann, 1959, et al.
(author)
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Effect of Enteral Lipid Supplement on Severe Retinopathy of Prematurity A Randomized Clinical Trial
- 2021
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In: JAMA Pediatrics. - : American Medical Association (AMA). - 2168-6203 .- 2168-6211. ; 175:4, s. 359-367
-
Journal article (peer-reviewed)abstract
- IMPORTANCE Lack of arachidonic acid (AA) and docosahexaenoic acid (DHA) after extremely preterm birth may contribute to preterm morbidity, including retinopathy of prematurity (ROP). OBJECTIVE To determine whether enteral supplementation with fatty acids from birth to 40 weeks' postmenstrual age reduces ROP in extremely preterm infants. DESIGN, SETTING, AND PARTICIPANTS The Mega Donna Mega trial, a randomized clinical trial, was a multicenter study performed at 3 university hospitals in Sweden from December 15, 2016, to December 15, 2019. The screening pediatric ophthalmologists were masked to patient groupings. A total of 209 infants born at less than 27 weeks' gestation were tested for eligibility, and 206 infants were included. Efficacy analyses were performed on as-randomized groups on the intention-to-treat population and on the per-protocol population using as-treated groups. Statistical analyses were performed from February to April 2020. INTERVENTIONS Infants received either supplementation with an enteral oil providing AA (100mg/kg/d) and DHA (50mg/kg/d) (AA:DHA group) or no supplementation within 3 days after birth until 40 weeks' postmenstrual age. MAIN OUTCOMES AND MEASURES The primary outcomewas severe ROP (stage 3 and/or type 1). The secondary outcomes were AA and DHA serum levels and rates of other complications of preterm birth. RESULTS A total of 101 infants (58 boys [57.4%]; mean [SD] gestational age, 25.5 [1.5] weeks) were included in the AA:DHA group, and 105 infants (59 boys [56.2%]; mean [SD] gestational age, 25.5 [1.4] weeks) were included in the control group. Treatment with AA and DHA reduced severe ROP compared with the standard of care (16 of 101 [15.8%] in the AA:DHA group vs 35 of 105 [33.3%] in the control group; adjusted relative risk, 0.50 [95% CI, 0.28-0.91]; P =.02). The AA:DHA group had significantly higher fractions of AA and DHA in serum phospholipids compared with controls (overall mean difference in AA:DHA group, 0.82 mol% [95% CI, 0.46-1.18 mol%]; P <.001; overall mean difference in control group, 0.13 mol% [95% CI, 0.01-0.24 mol%]; P =.03). There were no significant differences between the AA:DHA group and the control group in the rates of bronchopulmonary dysplasia (48 of 101 [47.5%] vs 48 of 105 [45.7%]) and of any grade of intraventricular hemorrhage (43 of 101 [42.6%] vs 42 of 105 [40.0%]). In the AA:DHA group and control group, respectively, sepsis occurred in 42 of 101 infants (41.6%) and 53 of 105 infants (50.5%), serious adverse events occurred in 26 of 101 infants (25.7%) and 26 of 105 infants (24.8%), and 16 of 101 infants (15.8%) and 13 of 106 infants (12.3%) died. CONCLUSIONS AND RELEVANCE This study found that, compared with standard of care, enteral AA:DHA supplementation lowered the risk of severe ROP by 50% and showed overall higher serum levels of both AA and DHA. Enteral lipid supplementation with AA:DHA is a novel preventive strategy to decrease severe ROP in extremely preterm infants.
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31. |
- Hellström, William, et al.
(author)
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C-Peptide Suppression during Insulin Infusion in the Extremely Preterm Infant Is Associated with Insulin Sensitivity
- 2019
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In: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 104:9, s. 3902-3910
-
Journal article (peer-reviewed)abstract
- Context: Little is known about the individual response of glucose-regulating factors to administration of exogenous insulin infusion in extremely preterm infants. Objective: To evaluate longitudinal serum concentrations of insulin, C-peptide, and plasma glucose levels in a high-frequency sampling regimen in extremely preterm infants treated with insulin because of hyperglycemia. Design: Prospective longitudinal cohort study. Setting: Two university hospitals in Sweden between December 2015 and September 2016. Patients and Intervention: Serum samples were obtained from nine extremely preterm infants, gestational age between 22 (+3) and 26 (+5) weeks (+ days), with hyperglycemia (plasma-glucose >10 mmol/L) at the start of insulin infusion, at 12, 24, and every 24 hours thereafter during ongoing infusion, and 12, 24, and 72 hours after the end of insulin infusion. Main outcome measures: Longitudinal serum concentrations of insulin and C-peptide and plasma glucose levels. Results: During insulin infusion, the serum C-peptide concentrations decreased compared with at start of infusion (P = 0.036), and then increased after ending the infusion. Individual insulin sensitivity based on the nonfasting plasma glucose/insulin ratio at the start of insulin infusion correlated with the initial decrease in serum ΔC-peptide[after 12h] (P = 0.007) and the degree of lasting decrease in serum ΔC-peptide[after end of infusion] (P = 0.015). Conclusion: Exogenous insulin infusion suppressed the C-peptide concentration to individually different degrees. In addition, the effect of insulin infusion on β cells may be linked to individual insulin sensitivity, where a low insulin sensitivity resulted in a more pronounced decrease in C-peptide during insulin infusion.
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32. |
- Hellström, William, et al.
(author)
-
Postnatal serum IGF-1 levels associate with brain volumes at term in extremely preterm infants
- 2023
-
In: Pediatric Research. - : Springer Science and Business Media LLC. - 0031-3998 .- 1530-0447. ; 93:3, s. 666-674
-
Journal article (peer-reviewed)abstract
- Background Growth factors important for normal brain development are low in preterm infants. This study investigated the link between growth factors and preterm brain volumes at term. Material/methods Infants born <28 weeks gestational age (GA) were included. Endogenous levels of insulin-like growth factor (IGF)-1, brain-derived growth factor, vascular endothelial growth factor, and platelet-derived growth factor (expressed as area under the curve [AUC] for serum samples from postnatal days 1, 7, 14, and 28) were utilized in a multivariable linear regression model. Brain volumes were determined by magnetic resonance imaging (MRI) at term equivalent age. Results In total, 49 infants (median [range] GA 25.4 [22.9-27.9] weeks) were included following MRI segmentation quality assessment and AUC calculation. IGF-1 levels were independently positively associated with the total brain (p < 0.001, beta = 0.90), white matter (p = 0.007, beta = 0.33), cortical gray matter (p = 0.002, beta = 0.43), deep gray matter (p = 0.008, beta = 0.05), and cerebellar (p = 0.006, beta = 0.08) volume adjusted for GA at birth and postmenstrual age at MRI. No associations were seen for other growth factors. Conclusions Endogenous exposure to IGF-1 during the first 4 weeks of life was associated with total and regional brain volumes at term. Optimizing levels of IGF-1 might improve brain growth in extremely preterm infants. Impact High serum levels of insulin-like growth factor (IGF)-1 during the first month of life were independently associated with increased total brain volume, white matter, gray matter, and cerebellar volume at term equivalent age in extremely preterm infants. IGF-1 is a critical regulator of neurodevelopment and postnatal levels are low in preterm infants. The effects of IGF-1 levels on brain development in extremely preterm infants are not fully understood. Optimizing levels of IGF-1 may benefit early brain growth in extremely preterm infants. The effects of systemically administered IGF-1/IGFBP3 in extremely preterm infants are now being investigated in a randomized controlled trial (Clinicaltrials.gov: NCT03253263).
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33. |
- Hildén, Karin, 1978-, et al.
(author)
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Born over 4500 g : the trends in birth trauma and mode of delivery in women with GDM and type 1 diabetes in Sweden between 1998-2012
- 2018
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Conference paper (peer-reviewed)abstract
- Background: We have previously shown that during the years 1998-2012, the overall incidence of LGA and birthweight decreased in both women with and without GDM in Sweden, and unpublished preliminary results show that there is a converse trend among women with T1DM. The incidence of Erbs palsy also decreased in the GDM and background population, but remained unchanged for women with T1DM. Since macrosomia is one of the most prominent risk factors for Erb´s palsy and delivery complications, the aim of the study was to evaluate trends in incidence of Erb´s palsy and delivery mode in the macrosomic group defined as weight ≥4500g and we present here our preliminary results.Method: This is a cohort study in Sweden 1998-2012 , including singleton macrosomic (≥4500 g) births. Vaginal deliveries were selected for the analyses relating to Erb´s plasy. Poisson regression was used to evaluate trends per year in both the GDM, T1DM and the background population. Results were partly stratified on BMI, to be able to detect any group differences in trends. P-value of <0.05 was considered statistically significant.Results: In total there were 57 2015 macrosomic infants, of whom (n= 36 933, 64,6%) were delivered vaginally. Of these, only 2.1 % (n=798) were vaginally delivered by women with GDM, (1.4%) type 2 diabetes (0.1%) or T1DM (0.7%). The trend in Erb´s palsy decreased significantly in the background population at a rate of OR 0.954 (95% CI 0.936-0.973) per year. For women with GDM or T1DM there was no significant change in incidence of trends over these years for Erb´s palsy. As for Caesarean section (CS) there was a significant increase per year for GDM pregnancies (OR 1.028, 95% CI 1.007-1.049) and in the background population (1.018 95% CI 1.013-1.022). No change was seen for CS in pregnancies with T1DM.Conclusion: Even though the rates of LGA and birthweight have decreased in Sweden over this time period for women with GDM and the background population, we could not see a significant decrease in Erb´s palsy among women with vaginal births in either the GDM group or for women with T1DM in the macrosomic infants. However, a decrease was seen in the incidence of Erb´s palsy in the macrosomic babies in the background population. The rates of CS have significantly increased in the background population and for GDM pregnancies, but been stable for T1DM. We conclude that the disparity in risk of Erbs has grown over this time period. Further work is needed to ascertain whether this is due to the need for improved surveillance, a higher CS rate, and/or improved glycaemic management (or other factors).
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34. |
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35. |
- Källén, Karin, et al.
(author)
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Ophthalmologic Outcome of Extremely Preterm Infants at 6.5 Years of Age Extremely Preterm Infants in Sweden Study (EXPRESS)
- 2016
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In: Jama Ophthalmology. - : American Medical Association (AMA). - 2168-6165 .- 2168-6173. ; 134:5, s. 555-562
-
Journal article (peer-reviewed)abstract
- IMPORTANCE This follow-up study of extremely preterm (EPT) children (<27 weeks' gestational age [GA] at birth) revealed major eye and visual problems in 37.9%(147 of 388) of all EPT infants and in 55.4%(67 of 121) of the most immature subgroups at 6.5 years of age. These major eye and visual problems were strongly associated with treatment-requiring retinopathy of prematurity (ROP). OBJECTIVES To investigate the ophthalmologic outcome of a national cohort of EPT children at 6.5 years of age and to evaluate the impact of prematurity and ROP. DESIGN, SETTING, AND PARTICIPANTS All surviving EPT children born in Sweden between April 1, 2004, and March 31, 2007, were included and compared with a matched term control group, as part of a prospective national follow-up study. MAIN OUTCOMES AND MEASURES Visual acuity, refraction in cycloplegia, and manifest strabismus were evaluated and compared with GA at birth and with treatment-requiring ROP. RESULTS The study cohort comprised 486 participants. The mean (SD) GA of the children who were included was 25 (1) weeks, and 45.7%(222 of 486) were female. At a median age of 6.6 years, 89.3%(434 of 486) of eligible EPT children were assessed and compared with 300 control group children. In the EPT group, 2.1%(9 of 434) were blind, 4.8%(21 of 434) were visually impaired according to the World Health Organization criteria, and 8.8% (38 of 434) were visually impaired according to the study criteria. Strabismus was found in 17.4% (68 of 390) and refractive errors in 29.7%(115 of 387) of the EPT children compared with 0% (0 of 299) and 5.9% (17 of 289), respectively, of the control children (P<.001). Altogether at 6.5 years of age, 37.9%(147 of 388) of the EPT children had some ophthalmologic abnormality compared with 6.2%(18 of 290) of the matched control group (95% CI of the difference, 26.1%-37.2%). When treatment-requiring ROP was adjusted for, no significant association between GA and visual impairment could be detected. For refractive errors, the association with GA remained after adjustment for treatment-requiring ROP (odds ratio, 0.72; 95% CI, 0.58-0.91 for each 1-week increment). CONCLUSIONS AND RELEVANCE In a Swedish national cohort of EPT children at 6.5 years of age, major eye and visual problems were frequently found. Treatment-requiring ROP was a stronger impact factor than GA on visual impairment and strabismus, but not on refractive errors, as a whole. In modern neonatal intensive care settings, ophthalmologic problems continue to account for a high proportion of long-term sequelae of prematurity.
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36. |
- Lasaviciute, Gintare, et al.
(author)
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Deficits in the IgG+ memory B‐cell recovery after anthracycline treatment is confined to the spleen of rhesus macaques
- 2020
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In: Clinical & Translational Immunology (CTI). - : Wiley. - 2050-0068. ; 9:7
-
Journal article (peer-reviewed)abstract
- Objectives. Loss of vaccine-induced antibodies (Abs) after chemotherapy against paediatric acute lymphoblastic leukaemia (ALL) is common and often necessitates re-immunisation after cessation of treatment. Even so, some ALL survivors fail to mount or to maintain protective Abs. Germinal centres (GCs) are clusters of proliferating B cells in follicles of secondary lymphoid tissues (SLTs) formed during adaptive immune responses and the origins of long-lived memory B and plasma cells that are the source of Abs. Furthermore, productive GC reactions depend on T follicular helper (TFH) cells. To understand why chemotherapy induces deficits in Ab responses, we examined how SLTs were affected by chemotherapy. Methods. Rhesus macaques were infused with either three cycles of the anthracycline doxorubicin or saline, followed by immunisation with a de novo and booster antigen. Spleen and lymph nodes were removed, and memory B, bulk T and TFH cells were examined. Results. Despite adequate GC morphology, a diminished memory and IgG+ B-cell population along with diminished total and booster vaccine-specific IgGproducing memory B cells were noted in the spleens of macaques with past doxorubicin exposure compared to the saline-treated controls (P < 0.05). Intact bulk T and TFH cells were found in the SLTs of treated macaques, which displayed higher CD40L upregulation capacity by their splenic CXCR5+ helper T cells (P < 0.01). In contrast to the spleen, the immune cell populations studied were comparable between the lymph nodes of both saline- and doxorubicin-treated macaques. Conclusion. Our findings suggest that the splenic memory B-cell subset, compared to its lymph node counterpart, is more severely altered by anthracycline treatment.
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37. |
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38. |
- Lindehammer, Sabina, et al.
(author)
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Temporal trends of HLA genotype frequencies of type 1 diabetes patients in Sweden from 1986 to 2005 suggest altered risk
- 2008
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In: Acta Diabetologica. - : Springer Science and Business Media LLC. - 0940-5429 .- 1432-5233. ; 45:4, s. 231-5
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Journal article (peer-reviewed)abstract
- The aim of this study was to compare the frequency of human leukocyte antigen (HLA) genotypes in 1-18-year-old patients with type 1 diabetes newly diagnosed in 1986-1987 (n = 430), 1996-2000 (n = 342) and in 2003-2005 (n = 171). We tested the hypothesis that the HLA DQ genotype distribution changes over time. Swedish type 1 diabetes patients and controls were typed for HLA using polymerase chain reaction amplification and allele specific probes for DQ A1* and B1* alleles. The most common type 1 diabetes HLA DQA1*-B1*genotype 0501-0201/0301-0302 was 36% (153/430) in 1986-1987 and 37% (127/342) in 1996-2000, but decreased to 19% (33/171) in 2003-2005 (P \ 0.0001). The 0501-0201/0501-0201 genotype increased from 1% in 1986-1987 to 7% in 1996-2000 (P = 0.0047) and to 5% in 2003-2005 (P > 0.05). This study in 1-18-year-old Swedish type 1 diabetes patients supports the notion that there is a temporal change in HLA risk.
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39. |
- Lindström, Karin M., et al.
(author)
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Feather mites and internal parasites in small ground finches (geospiza fuliginosa, emberizidae) from the galapagos Islands (Equador)
- 2009
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In: Journal of Parasitology. - 0022-3395 .- 1937-2345. ; 95:1, s. 39-45
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Journal article (peer-reviewed)abstract
- During a parasite survey, we collected data on the presence and distribution of feather mites, intestinal parasites, and blood parasites of small ground finches (Geospiza fuliginosa) from 4 islands in the Galapagos. We recorded 4 species of feather mites, with the most common species, Trouessartia geospiza, present on the majority (77% [308/400]) of individuals. Birds with high loads of T. geospiza came from larger islands and had higher body masses. We identified 3 species of intestinal Isospora (Isospora fragmenta, Isospora temeraria, and Isospora exigua) in fecal samples that showed a diurnal pattern of oocyst release. Among samples collected in the afternoon, infection prevalence was 61% (11/18), while only 0.5%a (1/192) contained oocysts in the morning. We screened 40 individuals from one island (Isabela) for blood parasites using molecular markers. Although no parasites of Haemoproteus, Leucocytozoon, or Plasmodium were detected, a high proportion of birds (80% [32/40]) had systemic Isospora spp. infections. A high infection prevalence (74% [20/27]), but low infection intensity, was confirmed using optical microscopy. This result could either be due to the detection of a previously unidentified systemic Isospora sp. parasite, or a result of the previously described Isospora spp. parasites causing systemic infections.
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40. |
- Ling, Charlotte, et al.
(author)
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Prolactin (PRL) receptor gene expression in mouse adipose tissue: increases during lactation and in PRL-transgenic mice
- 2000
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In: Endocrinology. - 0013-7227 .- 1945-7170. ; 141:10, s. 3564-3572
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Journal article (peer-reviewed)abstract
- There are indications that PRL may exert important metabolic actions on adipose tissue in different species. However, with the exception of birds, the receptor has not been identified in white adipose tissue. The present study was designed to examine the possible expression and regulation of the PRL receptor (PRLR) in mouse adipose tissue. The long PRLR messenger RNA (mRNA) splice form (L-PRLR) and two short splice forms (S2- and S3-PRLR) were detected in mouse adipose tissue by RT-PCR. Furthermore, L-PRLR mRNA was detected by ribonuclease protection assay. Immunoreactive PRLR with a relative molecular mass of 95,000 was revealed by immunoblotting. Furthermore, L-PRLR mRNA expression was demonstrated in primary isolated adipocytes. In mouse adipose tissue, the level of L-PRLR mRNA expression increased 2.3-fold during lactation compared with those in virgin and pregnant mice. In contrast, in the liver the expression of L-PRLR increased 3.4-fold during pregnancy compared with those in virgin and lactating mice. When comparing the levels of L-PRLR expression in virgin female and male mice, no difference was detected in adipose tissue. However, in virgin female liver the expression was 4.5-fold higher than that in male liver. As PRL up-regulates its own receptor in some tissues, we analyzed L-PRLR expression in PRL-transgenic female and male mice. In PRL-transgenic mice L-PRLR expression was significantly increased in both adipose tissue (1.4-fold in females and 2.4-fold in males) and liver (1.9-fold in females and 2.7-fold in males) compared with that in control mice. Furthermore, in female PRL-transgenic mice retroperitoneal adipose tissue was decreased in weight compared with that in control mice. However, no difference was detected when comparing the masses of parametrial adipose tissue. Our results suggest a direct role for PRL, mediated by PRLR, in modulating physiological events in adipose tissue.
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41. |
- Lundgren, Pia, 1967-, et al.
(author)
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Erythropoietin serum levels, versus anaemia as risk factors for severe retinopathy of prematurity
- 2019
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In: Pediatric Research. - : Nature Publishing Group. - 0031-3998 .- 1530-0447. ; 86:2, s. 276-282
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Journal article (peer-reviewed)abstract
- Background: Preterm infants with anaemia are treated with recombinant human erythropoietin (rhEPO). It is debated whether rhEPO treatment is a risk factor for retinopathy of prematurity (ROP). We evaluated longitudinal EPO and haemoglobin levels, blood transfusions and neonatal morbidities as risk factors for severe ROP.Method: This prospective study included 78 Swedish infants, born <28 weeks gestational age (GA), screened for ROP. We tested serum EPO levels on postnatal days 1, 7, 14 and 28 and at postmenstrual ages 32, 36 and 40 weeks. Haemoglobin levels and blood transfusions were recorded during postnatal weeks 1-4. Anaemia was defined as haemoglobin ≤110 g/L.Results: During postnatal week 1, infants with severe ROP requiring treatment (28%) more frequently developed anaemia (42.9% versus 8.0%, P = 0.003) and had higher mean EPO levels (postnatal day 7: 14.2 versus 10.8 mIU/mL, P = 0.003) compared to infants with no or less severe ROP not requiring treatment. In multivariable analyses, GA and anaemia during week 1 remained significant risk factors, but elevated EPO level postnatal day 7 was no longer significant.Conclusions: Among infants born <28 weeks GA, anaemia during week 1 was a significant risk factor for severe ROP requiring treatment but not elevated EPO levels.
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42. |
- Löfqvist, Chatarina, 1964, et al.
(author)
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Association of Retinopathy of Prematurity With Low Levels of Arachidonic Acid A Secondary Analysis of a Randomized Clinical Trial
- 2018
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In: Jama Ophthalmology. - : American Medical Association (AMA). - 2168-6165. ; 136:3, s. 271-277
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Journal article (peer-reviewed)abstract
- IMPORTANCE Mice with oxygen-induced retinopathy fed matched diets except for omega-3 long-chain polyunsaturated fatty acids (LC-PUFAs) vs omega-6 LC-PUFAs demonstrate relative antiangiogenic and neuroprotective associations of omega-3 LC-PUFAs. However, supplementing preterm infants with LC-PUFAs has been inconsistent in reducing major preterm morbidities. However, few studies measured serum lipid levels after supplementation. OBJECTIVE To examine the associated risk of retinopathy of prematurity (ROP) from the levels of circulating omega-3 and omega-6 LC-PUFAs. DESIGN, SETTING, AND PARTICIPANTS This longitudinal clinical study was a further analysis of serum lipid levels from a randomized controlled trial cohort of 90 infants born at gestational age (GA) less than 28 weeks. From April 4, 2013, to September 22, 2015, cord blood samples, followed by venous blood samples, were obtained at birth and at 1, 7, 14, and 28 days after birth and then at postmenstrual age (PMA) 32, 36, and 40 weeks at the neonatal intensive care unit at Sahlgrenska University Hospital in Goteborg, Sweden. MAIN OUTCOMES AND MEASURES Serum phospholipid fatty acids were transmethylated and measured by gas chromatography-mass spectrometry. Mann-Whitney test, logistic regression Spearman rank correlation, and receiver operating characteristic curve analysis were used to compare differences between infants with no ROP and infants who developed ROP. RESULTS Serum levels from 78 infants (43 male [55%]; mean [SD] GA, 25.5 [1.4] weeks) with a known ROP outcome were evaluated. Lower area under the curve (AUC) of arachidonic acid (AA) (20: 4 omega-6) was seen in infants with a later diagnosis of ROP compared with infants with no ROP in the first month of life (mean, 34.05 [95% CI, 32.10-36.00] vs 37.15 [95% CI, 34.85-39.46]; P < .05). In addition, lower levels of AA at 32 weeks' PMA were seen in infants with later severe ROP compared with in those without ROP (mean, 7.06 [95% CI, 6.60-7.52] vs 8.74 [95% CI, 7.80-9.67]; P < .001). In logistic modeling, low postnatal serum levels of AA and GA at birth identified with a sensitivity greater than 90% of infants who developed ROP. CONCLUSIONS AND RELEVANCE Low postnatal levels of the omega-6 LC-PUFAs (AA) are strongly associated with ROP development. Evaluating postnatal AA fraction after birth in addition to GA may be useful for ROP prediction.
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43. |
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44. |
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46. |
- Mercer, Louise K., et al.
(author)
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Spectrum of lymphomas across different drug treatment groups in rheumatoid arthritis : a European registries collaborative project
- 2017
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In: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 76:12, s. 2025-2030
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Journal article (peer-reviewed)abstract
- Background Lymphomas comprise a heterogeneous group of malignant diseases with highly variable prognosis. Rheumatoid arthritis (RA) is associated with a twofold increased risk of both Hodgkin’s lymphoma (HL) and non-Hodgkin’s lymphoma (NHL). It is unknown whether treatment with biologic disease-modifying antirheumatic drugs (bDMARDs) affect the risk of specific lymphoma subtypes.Methods Patients never exposed to (bionaïve) or ever treated with bDMARDs from 12 European biologic registers were followed prospectively for the occurrence of first ever histologically confirmed lymphoma. Patients were considered exposed to a bDMARD after having received the first dose. Lymphomas were attributed to the most recently received bDMARD.Results Among 124 997 patients (mean age 59 years; 73.7% female), 533 lymphomas were reported. Of these, 9.5% were HL, 83.8% B-cell NHL and 6.8% T-cell NHL. No cases of hepatosplenic T-cell lymphoma were observed. Diffuse large B-cell lymphoma (DLBCL) was the most frequent B-cell NHL subtype (55.8% of all B-cell NHLs). The subtype distributions were similar between bionaïve patients and those treated with tumour necrosis factor inhibitors (TNFi). For other bDMARDs, the numbers of cases were too small to draw any conclusions. Patients with RA developed more DLBCLs and less chronic lymphocytic leukaemia compared with the general population.Conclusion This large collaborative analysis of European registries has successfully collated subtype information on 533 lymphomas. While the subtype distribution differs between RA and the general population, there was no evidence of any modification of the distribution of lymphoma subtypes in patients with RA treated with TNFi compared with bionaïve patients.
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47. |
- Morin, Matilda, et al.
(author)
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Temporal trends in adverse pregnancy outcomes in axial spondyloarthritis in Sweden : a cohort study
- 2023
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In: The Lancet Rheumatology. - Stockholm : Karolinska Institutet, Dept of Medicine, Solna. - 2665-9913.
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Journal article (peer-reviewed)abstract
- Background: Evidence on the risks associated with pregnancy and childbirth in women with axial spondyloarthritis is scarce and conflicting, with more research needed to guide policy and clinical practice. We aimed to assess the risks of adverse pregnancy outcomes in a large cohort of women with axial spondyloarthritis, and to investigate how outcomes varied over time and in relation to anti-rheumatic treatment. Methods: In this register-based cohort study, we included births in Sweden between April 1, 2007, and Dec 31, 2020, to women with axial spondyloarthritis and general population comparators, matched 1:10 on year of delivery, maternal age, and parity. Our main data source was the Medical Birth Register (MBR), which includes over 98% of births in Sweden and prospectively collects data on antenatal care, delivery, and foetal outcomes. The information in MBR was linked to other registers, including the National Patient Register, the Prescribed Drug Register, and registers with demographic data. Our main outcomes were the relative risks of adverse pregnancy outcomes, analysed using modified Poisson regression. We also studied how the frequency of certain adverse outcomes, as well as disease-modifying antirheumatic drug (DMARD) and non-steroidal anti-inflammatory drug treatments, changed over the study period by linear regression and loess plots. Findings: Between April 1, 2007, and Dec 31, 2020, 1580 births in women with axial spondyloarthritis recorded in MBR fulfilled the inclusion criteria and were matched with 15 792 comparator births. Among the 1580 births in women with axial spondyloarthritis, we found increased risks of preterm birth (risk ratio 1.43, 95% CI 1.13-1.80), pre-eclampsia (1.44, 1.08-1.92), elective caesarean delivery (1.59, 1.37-1.84), and serious infant infection (1.29, 1.05-1.59) compared with births in general population comparators. The risks of preterm birth, infant infection, and caesarean delivery decreased by around 0.5 percentage points annually during the study period, while the use of tumour necrosis factor inhibitors during pregnancy increased. Interpretation: In view of remaining concerns regarding safety of the use of biological DMARDs during pregnancy, we saw a reassuring trend in which pregnancy outcomes improved over time in the axial spondyloarthritis group, concurrent with increased use of biological DMARDs. If the current rate of improvement is maintained, women with axial spondyloarthritis treated in accordance with clinical guidelines might eventually not be at an increased risk of adverse pregnancy outcomes.
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48. |
- Najm, Svetlana, et al.
(author)
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Effects of a lipid emulsion containing fish oil on polyunsaturated fatty acid profiles, growth and morbidities in extremely premature infants: A randomized controlled trial
- 2017
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In: Clinical Nutrition ESPEN. - : Elsevier BV. - 2405-4577. ; 20, s. 17-23
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Journal article (peer-reviewed)abstract
- © 2017 The Authors Background & aims The purpose of the study was to compare the effects of the parenteral emulsion SMOFlipid ® , with 15% fish oil, with Clinoleic ® on retinopathy of prematurity (ROP) and other morbidities and growth, and to compare their impact on longitudinal serum levels of fatty acids. Retinopathy of prematurity, other morbidity and growth were correlated with each parenteral lipid supplement. Methods Ninety infants born at gestational age < 28 weeks were randomized to treatment with SMOFlipid ® or Clinoleic ® . Two thirds (66%) of the infants received parenteral nutrition for up to 14 days birth (median 8, range 2–14 days), and additional 25% of the infants received for up to 28 days after birth (median 21, range 15–28 days). Cord blood samples and then venous blood samples were obtained at ages 1, 7, 14, and 28 days and at postmenstrual age (PMA) 32, 36, and 40 weeks. Breastmilk was collected at postnatal day 7, and at PMA 32 and 40 weeks. Serum phospholipid and breastmilk total fatty acids were analyzed by gas chromatography–mass spectrometry. Treatment groups were compared with regard to ROP, bronchopulmonary dysplasia, necrotizing enterocolitis, patent ductus arteriosus sepsis and growth between birth and 36 weeks. Results Infants on SMOFlipid ® had higher fractions of omega-3 LCPUFA eicosapentaenoic acid (EPA) and slightly higher omega-3 LCPUFA docosahexaenoic acid (DHA) fraction and a decreased arachidonic acid (AA) to DHA ratio from one week after birth up to 32 postmenstrual weeks compared to infants on Clinoleic ® . Treatment groups did not differ in morbidities or growth. Conclusion Supplementation with SMOFlipid ® containing 15% fish oil during parenteral nutrition increased EPA substantially, DHA marginally, reduced AA and decreased AA to DHA ratio. It did not reduce morbidity or affect growth. Since extremely preterm infants accumulate a large deficit of DHA and AA, studies on more prolonged or different levels of DHA and AA supplementation are warranted.
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49. |
- Nilsson, Anders K., 1982, et al.
(author)
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Influence of Human Milk and Parenteral Lipid Emulsions on Serum Fatty Acid Profiles in Extremely Preterm Infants.
- 2019
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In: JPEN - Journal of Parenteral and Enteral Nutrition. - : Wiley. - 0148-6071 .- 1941-2444. ; 43:1, s. 152-161
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Journal article (peer-reviewed)abstract
- Infants born prematurely are at risk of a deficiency in ω-6 and ω-3 long-chain polyunsaturated fatty acids (LC-PUFAs) arachidonic acid (AA) and docosahexaenoic acid (DHA). We investigated how fatty acids from breast milk and parenteral lipid emulsions shape serum LC-PUFA profiles in extremely preterm infants during early perinatal life.Ninety infants born < 28 weeks gestational age were randomized to receive parenteral lipids with or without the ω-3 LC-PUFAs eicosapentaenoic acid (EPA) and DHA (SMOFlipid: Fresenius Kabi, Uppsala, Sweden, or Clinoleic: Baxter Medical AB, Kista, Sweden, respectively). The fatty acid composition of infant serum phospholipids was determined from birth to postmenstrual age 40 weeks, and in mother's milk total lipids on postnatal day 7. Enteral and parenteral intake of LC-PUFAs was correlated with levels in infant serum.Infants administered parenteral ω-3 LC-PUFAs received 4.4 and 19.3 times more DHA and EPA, respectively, over the first 2 weeks of life. Parenteral EPA but not DHA correlated with levels in infant serum. We found linear relationships between dietary EPA and DHA and infant serum levels in the Clinoleic (Baxter Medical AB) group. The volume of administered SMOFlipid (Fresenius Kabi) was inversely correlated with serum AA, whereas Clinoleic (Baxter Medical AB) inversely correlated with serum EPA and DHA.There appears to be no or low correlation between the amount of DHA administered parenterally and levels measured in serum. Whether this observation reflects serum phospholipid fraction only or truly represents the amount of accreted DHA needs to be investigated. None of the parenteral lipid emulsions satisfactorily maintained high levels of both ω-6 and ω-3 LC-PUFAs in infant serum.
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50. |
- Nilsson, Anders K., 1982, et al.
(author)
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Long-chain polyunsaturated fatty acids decline rapidly in milk from mothers delivering extremely preterm indicating the need for supplementation.
- 2018
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In: Acta paediatrica. - : Wiley. - 1651-2227 .- 0803-5253. ; 107:6, s. 1020-1027
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Journal article (peer-reviewed)abstract
- Our aim was perform an in-depth analysis of the composition of fatty acids in milk from mothers delivering extremely preterm babies. We investigated longitudinal changes in milk fatty acid profiles and the relationship between several types of fatty acids, including omega-3 and omega-6.Milk samples were collected at three stages of lactation from 78 mothers who delivered at less than 28 weeks of pregnancy at the Sahlgrenska University Hospital, Gothenburg, Sweden, from April 2013 to September 2015. Fatty acid composition was analysed by gas chromatography-mass spectrometry.A reduction in long-chain polyunsaturated fatty acids (LCPUFAs) was observed during the lactation period. The concentrations of arachidonic acid and docosahexaenoic acid declined from medians of 0.34 to 0.22 mol% and 0.29 to 0.15 mol%, respectively, between postnatal day seven and a post-menstrual age of 40 weeks. Strong correlations were found between the intermediates of several classes of fatty acids, including omega-3, omega-6 and omega-9.A rapid reduction in LCPUFA content in the mother's milk during the lactation period emphasises the importance of fatty acid supplementation to infants born extremely preterm, at least during the period corresponding to the third trimester, when rapid development of the brain and adipose tissue require high levels of LCPUFAs. This article is protected by copyright. All rights reserved.
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