| 1. |
- Alkmark, Mårten, 1973, et al.
(författare)
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Efficacy and safety of oral misoprostol versus transvaginal balloon catheter for labor induction: An observational study within the SWEdish Postterm Induction Study (SWEPIS)
- 2021
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Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 0001-6349 .- 1600-0412. ; 100:8, s. 1463-1477
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Induction of labor is increasing. A common indication for induction of labor is late term and postterm pregnancy at 41 weeks or more. We aimed to evaluate if there are any differences regarding efficacy, safety, and women's childbirth experience between oral misoprostol and transvaginal balloon catheter for cervical ripening in women with a low-risk singleton pregnancy and induction of labor at 41(+0) to 42(+0 to 1) weeks of gestation. Material and methods In this observational study, based on data from the Swedish Postterm Induction Study (SWEPIS), a multicenter randomized controlled trial, a total of 1213 women with a low-risk singleton pregnancy at 41 to 42 weeks of gestation were induced with oral misoprostol (n = 744) or transvaginal balloon catheter (n = 469) at 15 Swedish delivery hospitals. The primary efficacy outcome was vaginal delivery within 24 h and primary safety outcomes were neonatal and maternal composite adverse outcomes. Secondary outcomes included time to vaginal delivery and mode of delivery. Women's childbirth experience was assessed with the Childbirth Experience Questionnaire (CEQ 2.0) and visual analog scale. We present crude and adjusted mean differences and relative risks (RR) with 95% CI. Adjustment was performed for a propensity score based on delivery hospital and baseline characteristics including Bishop score. Results Vaginal delivery within 24 h was significantly lower in the misoprostol group compared with the balloon catheter group (46.5% [346/744] versus 62.7% [294/469]; adjusted RR 0.76 95% CI 0.640.89]). Primary neonatal and maternal safety outcomes did not differ between groups (neonatal composite 3.5% [36/744] vs 3.2% [15/469]; adjusted RR 0.77 [95% CI 0.31-1.89]; maternal composite 2.3% [17/744] versus 1.9% [9/469]; adjusted RR 1.70 [95% CI 0.58-4.97]). Adjusted mean time to vaginal delivery was increased by 3.8 h (95% CI 1.3-6.2 h) in the misoprostol group. Non-operative vaginal delivery and cesarean delivery rates did not differ. Women's childbirth experience was positive overall and similar in both groups. Conclusion Induction of labor with oral misoprostol compared with a transvaginal balloon catheter was associated with a lower probability of vaginal delivery within 24 h and a longer time to vaginal delivery. However, primary safety outcomes, non-operative vaginal delivery, and women's childbirth experience were similar in both groups. Therefore, both methods can be recommended in women with low-risk postdate pregnancies.
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| 2. |
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| 3. |
- Alkmark, Mårten, 1973, et al.
(författare)
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Induction of labour at 41 weeks or expectant management until 42 weeks: A systematic review and an individual participant data meta-analysis of randomised trials.
- 2020
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Ingår i: PLoS medicine. - : Public Library of Science (PLoS). - 1549-1676 .- 1549-1277. ; 17:12
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Tidskriftsartikel (refereegranskat)abstract
- The risk of perinatal death and severe neonatal morbidity increases gradually after 41 weeks of pregnancy. Several randomised controlled trials (RCTs) have assessed if induction of labour (IOL) in uncomplicated pregnancies at 41 weeks will improve perinatal outcomes. We performed an individual participant data meta-analysis (IPD-MA) on this subject.We searched PubMed, Excerpta Medica dataBASE (Embase), The Cochrane Library, Cumulative Index of Nursing and Allied Health Literature (CINAHL), and PsycINFO on February 21, 2020 for RCTs comparing IOL at 41 weeks with expectant management until 42 weeks in women with uncomplicated pregnancies. Individual participant data (IPD) were sought from eligible RCTs. Primary outcome was a composite of severe adverse perinatal outcomes: mortality and severe neonatal morbidity. Additional outcomes included neonatal admission, mode of delivery, perineal lacerations, and postpartum haemorrhage. Prespecified subgroup analyses were conducted for parity (nulliparous/multiparous), maternal age (<35/≥35 years), and body mass index (BMI) (<30/≥30). Aggregate data meta-analysis (MA) was performed to include data from RCTs for which IPD was not available. From 89 full-text articles, we identified three eligible RCTs (n = 5,161), and two contributed with IPD (n = 4,561). Baseline characteristics were similar between the groups regarding age, parity, BMI, and higher level of education. IOL resulted overall in a decrease of severe adverse perinatal outcome (0.4% [10/2,281] versus 1.0% [23/2,280]; relative risk [RR] 0.43 [95% confidence interval [CI] 0.21 to 0.91], p-value 0.027, risk difference [RD] -57/10,000 [95% CI -106/10,000 to -8/10,000], I2 0%). The number needed to treat (NNT) was 175 (95% CI 94 to 1,267). Perinatal deaths occurred in one (<0.1%) versus eight (0.4%) pregnancies (Peto odds ratio [OR] 0.21 [95% CI 0.06 to 0.78], p-value 0.019, RD -31/10,000, [95% CI -56/10,000 to -5/10,000], I2 0%, NNT 326, [95% CI 177 to 2,014]) and admission to a neonatal care unit ≥4 days occurred in 1.1% (24/2,280) versus 1.9% (46/2,273), (RR 0.52 [95% CI 0.32 to 0.85], p-value 0.009, RD -97/10,000 [95% CI -169/10,000 to -26/10,000], I2 0%, NNT 103 [95% CI 59 to 385]). There was no difference in the rate of cesarean delivery (10.5% versus 10.7%; RR 0.98, [95% CI 0.83 to 1.16], p-value 0.81) nor in other important perinatal, delivery, and maternal outcomes. MA on aggregate data showed similar results. Prespecified subgroup analyses for the primary outcome showed a significant difference in the treatment effect (p = 0.01 for interaction) for parity, but not for maternal age or BMI. The risk of severe adverse perinatal outcome was decreased for nulliparous women in the IOL group (0.3% [4/1,219] versus 1.6% [20/1,264]; RR 0.20 [95% CI 0.07 to 0.60], p-value 0.004, RD -127/10,000, [95% CI -204/10,000 to -50/10,000], I2 0%, NNT 79 [95% CI 49 to 201]) but not for multiparous women (0.6% [6/1,219] versus 0.3% [3/1,264]; RR 1.59 [95% CI 0.15 to 17.30], p-value 0.35, RD 27/10,000, [95% CI -29/10,000 to 84/10,000], I2 55%). A limitation of this IPD-MA was the risk of overestimation of the effect on perinatal mortality due to early stopping of the largest included trial for safety reasons after the advice of the Data and Safety Monitoring Board. Furthermore, only two RCTs were eligible for the IPD-MA; thus, the possibility to assess severe adverse neonatal outcomes with few events was limited.In this study, we found that, overall, IOL at 41 weeks improved perinatal outcome compared with expectant management until 42 weeks without increasing the cesarean delivery rate. This benefit is shown only in nulliparous women, whereas for multiparous women, the incidence of mortality and morbidity was too low to demonstrate any effect. The magnitude of risk reduction of perinatal mortality remains uncertain. Women with pregnancies approaching 41 weeks should be informed on the risk differences according to parity so that they are able to make an informed choice for IOL at 41 weeks or expectant management until 42 weeks. Study Registration: PROSPERO CRD42020163174.
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| 4. |
- Alkmark, Mårten, 1973, et al.
(författare)
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Induction of labour at 41weeks of gestation versus expectant management and induction of labour at 42weeks of gestation: a cost-effectiveness analysis
- 2022
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Ingår i: BJOG: An International Journal of Obstetrics and Gynaecology. - : Wiley. - 1470-0328 .- 1471-0528. ; 129:13, s. 2157-2165
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To assess the cost-effectiveness of induction of labour (IOL) at 41weeks of gestation compared with expectant management until 42weeks of gestation. Design: A cost-effectiveness analysis alongside the Swedish Post-term Induction Study (SWEPIS), a multicentre, randomised controlled superiority trial. Setting: Fourteen Swedish hospitals during 2016–2018. Population: Women with an uncomplicated singleton pregnancy with a fetus in cephalic position were randomised at 41weeks of gestation to IOL or to expectant management and induction at 42weeks of gestation. Methods: Health benefits were measured in life years and quality-adjusted life years (QALYs) for mother and child. Total cost per birth was calculated, including healthcare costs from randomisation to discharge after delivery, for mother and child. Incremental cost-effectiveness ratios (ICERs) were calculated by dividing the difference in mean cost between the trial arms by the difference in life years and QALYs, respectively. Sampling uncertainty was evaluated using non-parametric bootstrapping. Main outcome measures: The cost per gained life year and per gained QALY. Results: The differences in life years and QALYs gained were driven by the difference in perinatal mortality alone. The absolute risk reduction in mortality was 0.004 (from 6/1373 to 0/1373). Based on Swedish life tables, this gives a mean gain in discounted life years and QALYs of 0.14 and 0.12 per birth, respectively. The mean cost per birth was €4108 in the IOL group (n=1373) and €4037 in the expectant management group (n=1373), with a mean difference of €71 (95%CI −€232 to €379). The ICER for IOL compared with expectant management was €545 per life year gained and €623 per QALY gained. Confidence intervals were relatively wide and included the possibility that IOL had both lower costs and better health outcomes. Conclusions: Induction of labour at 41weeks of gestation results in a better health outcome and no significant difference in costs. IOL is cost-effective compared with expectant management until 42weeks of gestation using standard threshold values for acceptable cost per life year/QALY. Tweetable abstract: Induction of labour at 41weeks of gestation is cost-effective compared with expectant management until 42weeks of gestation.
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| 5. |
- Alkmark, Mårten, 1973
(författare)
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Management of late term pregnancy
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: The optimal time point to intervene and induce labour in women with a low-risk pregnancy, in order to decrease perinatal adverse outcome, is up for debate. Some advocate for induction of labour (IOL) at 41 gestational weeks (GW) and others for expectant management (EM) until 42 GW. Aim: To clarify, in women with a low-risk singleton pregnancy, if a policy of IOL at 41 GW (late term) compared with EM until 42 GW (postterm) was superior, in terms of neonatal and maternal outcomes, as well as health economic aspects. Furthermore, different methods of IOL in late term/postterm pregnancies were assessed. Material and methods: Paper I was a Swedish multicentre register-based randomised controlled trial in women with a low-risk late term/postterm singleton pregnancy (n=2 760) comparing IOL at 41 GW with EM until 42 GW. The trial was conducted between May 2016 and October 2018. Primary outcome was a composite of perinatal mortality and morbidity. Paper II was a one-step individual participant data (IPD) meta-analysis (n=5 161 for aggregate data and 4 561 for IPD) and included trials comparing IOL in women with a low-risk singleton pregnancy at 41 GW with EM until 42 GW. Primary outcome was a composite of perinatal morbidity and mortality. Subgroup analysis was performed on maternal age, body mass index and parity. Paper III was a cost-effectiveness analysis alongside Paper I (n=2 746). Primary outcomes were costs per gained life year (LY) and quality adjusted life year (QALY). Paper IV was a prospective cohort study on efficacy, safety and women’s childbirth experience of IOL with oral misoprostol (OM) (n=744) compared with transvaginal balloon catheter (TVBC) (n=469). Women included in Paper I, who needed cervical ripening for IOL, were assessed. Primary efficacy outcome was vaginal delivery within 24 hours, primary safety outcomes were a composite of neonatal mortality and morbidity and a composite of maternal mortality and morbidity. Women’s childbirth experience was measured with the Childbirth Experience Questionnaire (CEQ 2.0). Results: Paper I: The primary outcome did not differ between the groups. However, the trial was truncated early due to safety reasons because a significant decreased perinatal mortality was seen in the IOL group (p=0.03). Similar results in both groups were reported regarding mode of delivery and maternal adverse outcomes, except endometritis. Paper II: Three trials were eligible and two contributed with IPD. The primary outcome was significantly lower in the IOL group, relative risk (RR) 0.43 (95 % confidence interval [CI] 0.21 to 0.91), as were perinatal mortality, Peto odds ratio 0.21 (95 % CI 0.06 to 0.78) and admission to neonatal care ≥4 days, RR 0.52 (95 % CI 0.32 to 0.85). Similar results in both groups were reported regarding mode of delivery and maternal adverse outcomes. The primary outcome was significantly lower in the IOL group in nulliparous, but not in parous women. Paper III: The incremental cost-effectiveness ratio for IOL compared with EM was €545 per LY (95 % CI ranging from lower costs and better health outcomes [dominant] to €4 002) and €623 per QALY (95 % CI dominant to €4 586). Paper IV: Vaginal delivery within 24 hours was significantly lower in the OM group compared with the TVBC group, adjusted RR 0.76 (95 % CI 0.64; 0.89). Primary neonatal and maternal safety outcomes did not differ between groups. Women’s childbirth experience was overall positive and similar in the groups. Conclusion: There are medical benefits of IOL at 41 GW compared with EM until 42 GW and it is cost-effective. TVBC was slightly more effective regarding efficacy. Women approaching 41+0 GW should receive unbiased information regarding benefits and risks with IOL at 41+0 GW compared with EM in order to make an informed decision for herself and her unborn infant.
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| 6. |
- Schang, Anne-Laure, et al.
(författare)
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Failure of thyroid hormone treatment to prevent inflammation-induced white matter injury in the immature brain.
- 2014
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Ingår i: Brain, behavior, and immunity. - : Elsevier BV. - 1090-2139 .- 0889-1591. ; 37, s. 95-102
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Tidskriftsartikel (refereegranskat)abstract
- Preterm birth is very strongly associated with maternal/foetal inflammation and leads to permanent neurological deficits. These deficits correlate with the severity of white matter injury, including maturational arrest of oligodendrocytes and hypomyelination. Preterm birth and exposure to inflammation causes hypothyroxinemia. As such, supplementation with thyroxine (T4) seems a good candidate therapy for reducing white matter damage in preterm infants as oligodendrocyte maturation and myelination is regulated by thyroid hormones. We report on a model of preterm inflammation-induced white matter damage, in which induction of systemic inflammation by exposure from P1 to P5 to interleukin-1β (IL-1β) causes oligodendrocyte maturational arrest and hypomyelination. This model identified transient hypothyroidism and wide-ranging dysfunction in thyroid hormone signalling pathways. To test whether a clinically relevant dose of T4 could reduce inflammation-induced white matter damage we concurrently treated mice exposed to IL-1β from P1 to P5 with T4 (20μg/kg/day). At P10, we isolated O4-positive pre-oligodendrocytes and gene expression analysis revealed that T4 treatment did not recover the IL-1β-induced blockade of oligodendrocyte maturation. Moreover, at P10 and P30 immunohistochemistry for markers of oligodendrocyte lineage (NG2, PDGFRα and APC) and myelin (MBP) similarly indicated that T4 treatment did not recover IL-1β-induced deficits in the white matter. In summary, in this model of preterm inflammation-induced white matter injury, a clinical dose of T4 had no therapeutic efficacy. We suggest that additional pre-clinical trials with T4 covering the breadth and scope of causes and outcomes of perinatal brain injury are required before we can correctly evaluate clinical trials data and understand the potential for thyroid hormone as a widely implementable clinical therapy.
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