| 1. |
- Kuusela, Pihla, et al.
(författare)
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Second trimester cervical length measurements with transvaginal ultrasound : a prospective observational agreement and reliability study
- 2020
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Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - : John Wiley & Sons. - 0001-6349 .- 1600-0412. ; 99:11, s. 1476-1485
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Universal screening for preterm delivery by adding transvaginal ultrasound measurement of cervical length to routine second trimester ultrasound has been proposed. The aim is to estimate inter- and intra-observer agreement and reliability of second trimester transvaginal ultrasound measurements of cervical length performed by specially trained midwife sonographers.MATERIAL AND METHODS: This is a prospective reliability and agreement study performed in seven Swedish ultrasound centers. In total, 18 midwife sonographers specially trained to perform ultrasound measurements of cervical length and 286 women in the second trimester were included. In each center two midwife sonographers measured cervical length a few minutes apart in the same woman, the number of women examined per examiner pair varying between 24 and 30 (LIVE study). Sixteen midwife sonographers measured cervical length twice ≥2 months apart on 93 video-clips (CLIPS study). The main outcome measures were mean difference, limits of agreement, intra-class correlation coefficient, intra-individual standard deviation, repeatability, Cohen´s kappa, and Fleiss kappa.RESULTS: The limits of agreement and intra-class correlation coefficient of the best examiner pair in the LIVE study were -4.06 to 4.72 mm and 0.91, those of the poorest were -11.11 to 11.39 mm and 0.31. In the CLIPS study, median (range) intra-individual standard deviation was 2.14 mm (1.40 to 3.46), repeatability 5.93 mm (3.88 to 9.58), intra-class correlation coefficient 0.84 (0.66 to 0.94). Median (range) inter-observer agreement for cervical length ≤25 mm in the CLIPS study was 94.6% (84.9% to 98.9%) and Cohen´s kappa 0.56 (0.12 to 0.92), median (range) intra-observer agreement was 95.2% (87.1% to 98.9%) and Cohen´s kappa 0.68 (0.27 to 0.93).CONCLUSIONS: Agreement and reliability of cervical length measurements differed substantially between examiner pairs and examiners. If cervical length measurements are used to guide management there is potential for both over- and under-treatment. Uniform training and rigorous supervision and quality control are advised.
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| 2. |
- Kuusela, Pihla, et al.
(författare)
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Second trimester transvaginal ultrasound measurement of cervical length for prediction of preterm birth : a blinded prospective multicentre diagnostic accuracy study
- 2021
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Ingår i: British Journal of Obstetrics and Gynecology. - : Wiley-Blackwell Publishing Inc.. - 1470-0328 .- 1471-0528. ; 128:2, s. 195-206
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To estimate the diagnostic performance of sonographic cervical length for prediction of preterm birth (PTB).DESIGN: Prospective observational multicentre study.SETTING: Seven Swedish ultrasound centres.SAMPLE: 11456 asymptomatic women with a singleton pregnancy.METHODS: Cervical length was measured with transvaginal ultrasound at 18 to 20 weeks (Cx1) and at 21 to 23 weeks (Cx2; optional). Staff and participants were blinded to results.MAIN OUTCOME MEASURES: Area under receiver operating characteristic curve (AUC), sensitivity, specificity, positive and negative predictive values (PPV, NPV), positive and negative likelihood ratios (LR+, LR-), number of false positive results per true positive result (FP/TP), number needed to screen to detect one PTB (NNS), prevalence of "short" cervix.RESULTS: Spontaneous PTB (sPTB) <33 weeks occurred in 56/11072 (0.5%) women in the Cx1 population (89% white ethnicity) and in 26/6288 (0.4%) in the Cx2 population (92% white ethnicity). The discriminative ability of shortest endocervical length was better the earlier the sPTB occurred and better at Cx2 than at Cx1 (AUC to predict sPTB <33 weeks 0.76 versus 0.65, difference in AUC 0.11, 95% CI 0.01 to 0.23). At Cx2, shortest endocervical length ≤25 mm (prevalence 4.4%) predicted sPTB <33 weeks with sensitivity 38.5% (10/26), specificity 95.8% (5998/6262), PPV 3.6% (10/274), NPV 99.7% (5988/6014), LR+ 9.1, LR- 0.64, 26 FP/TP, 629 NNS.CONCLUSION: Second trimester sonographic cervical length can identify women at high risk of sPTB. In a population of mainly white women and low prevalence of sPTB its diagnostic performance is at best moderate.
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| 3. |
- Thorell, Anna, et al.
(författare)
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Microbial invasion of the amniotic cavity is associated with impaired cognitive and motor function at school age in preterm children.
- 2020
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Ingår i: Pediatric research. - : Springer Science and Business Media LLC. - 1530-0447 .- 0031-3998. ; 87:5, s. 924-931
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Tidskriftsartikel (refereegranskat)abstract
- Chorioamnionitis is an important cause of preterm delivery. Data on neurodevelopmental outcome in exposed infants are inconsistent due to difficulties in diagnosing intrauterine infection/inflammation and lack of detailed long-term follow-up. We investigate cognitive and motor function in preterm infants at early school age and relate the findings to bacteria in amniotic fluid obtained by amniocentesis (microbial invasion of the amniotic cavity (MIAC)) or placenta findings of histological chorioamnionitis (HCA) or fetal inflammatory response syndrome (FIRS).Sixty-six infants with gestational age <34 weeks at birth and without major disabilities were assessed using WISC-III and the Bruininks-Oseretsky Test of Motor Proficiency. Results were corrected for gestational age and sex.Children exposed to MIAC had significantly lower scores for full-scale IQ and verbal IQ compared to the non-MIAC group and the difference in full-scale IQ remained after correction for confounding factors. The MIAC group had also significantly lower motor scores after correction. In contrast, motor function was not affected in infants exposed to HCA or FIRS and differences between groups for cognitive scores were lost after corrections.Exposure to bacteria in amniotic fluid is associated with lower motor and cognitive scores in school age preterm infants without major disabilities.
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| 4. |
- Wikström, T., et al.
(författare)
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Cost-effectiveness of cervical length screening and progesterone treatment to prevent spontaneous preterm delivery in Sweden
- 2022
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Ingår i: Ultrasound in Obstetrics and Gynecology. - : Wiley. - 0960-7692 .- 1469-0705. ; 59:6, s. 778-792
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To estimate the cost-effectiveness of strategies to prevent spontaneous preterm delivery (PTD) in asymptomatic singleton pregnancies, using prevalence and healthcare cost data from the Swedish healthcare context. Methods: We designed a decision analytic model based on the Swedish CERVIX study to estimate the cost-effectiveness of strategies to prevent spontaneous PTD in asymptomatic women with a singleton pregnancy. The model was constructed as a combined decision-tree model and Markov model with a time horizon of 100 years. Four preventive strategies, namely ‘Universal screening’, ‘High-risk-based screening’ (i.e. screening of high-risk women only), ‘Low-risk-based screening’ (i.e. treatment of high-risk population and screening of remaining women) and ‘Nullipara screening’ (i.e. treatment of high-risk population and screening of nulliparous women only), included second-trimester cervical length (CL) screening by transvaginal ultrasound followed by vaginal progesterone treatment in the case of a short cervix. A fifth preventive strategy involved vaginal progesterone treatment of women with previous spontaneous PTD or late miscarriage but no CL screening (‘No screening, treat high-risk group’). For comparison, we used a sixth strategy implying no specific intervention to prevent spontaneous PTD, reflecting the current situation in Sweden (‘No screening’). Probabilities for a short cervix (CL ≤ 25 mm; base-case) and for spontaneous PTD at < 33 + 0 weeks and at 33 + 0 to 36 + 6 weeks were derived from the CERVIX study, and probabilities for stillbirth, neonatal mortality and long-term morbidity (cerebral palsy) from Swedish health data registers. Costs were based on Swedish data, except costs for cerebral palsy, which were based on Danish data. We assumed that vaginal progesterone reduces spontaneous PTD before 33 weeks by 30% and spontaneous PTD at 33–36 weeks by 10% (based on the literature). All analyses were from a societal perspective. We expressed the effectiveness of each strategy as gained quality-adjusted life years (QALYs) and presented cost-effectiveness as average (ACER; average cost per gained QALY compared with ‘No screening’) and incremental (ICER; difference in costs divided by the difference in QALYs for each of two strategies being compared) cost-effectiveness ratios. We performed deterministic and probabilistic sensitivity analysis. The results of the latter are shown as cost-effectiveness acceptability curves. Willingness-to-pay was set at a maximum of 500 000 Swedish krona (56 000 US dollars (USD)), as suggested by the Swedish National Board of Health and Welfare. Results: All interventions had better health outcomes than did ‘No screening’, with fewer screening-year deaths and more lifetime QALYs. The best strategy in terms of improved health outcomes was ‘Low-risk-based screening’, irrespective of whether screening was performed at 18 + 0 to 20 + 6 weeks (Cx1) or at 21 + 0 to 23 + 6 weeks (Cx2). ‘Low-risk-based screening’ at Cx1 was cost-effective, while ‘Low-risk-based screening’ at Cx2 entailed high costs compared with other alternatives. The ACERs were 2200 USD for ‘Low-risk-based screening’ at Cx1 and 36 800 USD for ‘Low-risk-based screening’ at Cx2. Cost-effectiveness was particularly sensitive to progesterone effectiveness and to productivity loss due to sick leave during pregnancy. The probability that ‘Low-risk-based screening’ at Cx1 is cost-effective compared with ‘No screening’ was 71%. Conclusion: Interventions to prevent spontaneous PTD in asymptomatic women with a singleton pregnancy, including CL screening with progesterone treatment of cases with a short cervix, may be cost-effective in Sweden.
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| 5. |
- Wikström, Tove, et al.
(författare)
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Effect of second-trimester sonographic cervical length on the risk of spontaneous preterm delivery in different risk groups : a prospective observational multicenter study
- 2021
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Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - : John Wiley & Sons. - 0001-6349 .- 1600-0412. ; 100:9, s. 1644-1655
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: The aim of the study is to compare the effect of cervical length measured with transvaginal ultrasound in the second trimester on the risk of spontaneous preterm delivery between different risk groups of asymptomatic women with a singleton pregnancy.MATERIAL AND METHODS: This is a pre-planned exploratory analysis of the CERVIX study, a prospective blinded multicenter diagnostic accuracy study. Asymptomatic women with a singleton pregnancy were consecutively recruited at their second-trimester routine ultrasound examination at seven Swedish ultrasound centers. Cervical length was measured with transvaginal ultrasound at 18-20 weeks (Cx1; n=11 072) and 21-23 weeks (Cx2, optional; n=6288). The effect of cervical length on the risk of spontaneous preterm delivery and its discriminative ability was compared between women with: i. previous spontaneous preterm delivery, late miscarriage or cervical conization (high-risk group; n=1045); ii. nulliparae without risk factors (n=5173); iii. parae without risk factors (n=4740). Women with previous indicated preterm delivery were excluded (n=114). Main outcome measures were: effect of cervical length on the risk of spontaneous preterm delivery expressed as odds ratio per 5 mm decrease in cervical length with interaction analysis using logistic regression to test if the effect differed between groups, area under the receiver operating characteristic curve (AUC), sensitivity, specificity, number needed to screen to detect one spontaneous preterm delivery.RESULTS: The effect of cervical length at Cx2 on the risk of spontaneous preterm delivery <33 weeks was similar in all groups (odds ratios 2.26 to 2.58, interaction P-value 0.91). The discriminative ability at Cx2 was superior to that at Cx1 and was similar in all groups (AUC 0.69 to 0.76). Cervical length ≤25 mm at Cx2 identified 57% of spontaneous preterm deliveries <33 weeks in the high-risk group with number needed to screen 161. The number needed to screen for groups ii and iii were 1018 and 843.CONCLUSIONS: The effect of cervical length at 21-23 weeks on the risk of spontaneous preterm delivery <33 weeks is similar in high- and low-risk pregnancies. The differences in number needed to screen should be considered before implementing a screening program.
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| 6. |
- Wikström, Tove, et al.
(författare)
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Microbial and human transcriptome in vaginal fluid at midgestation: Association with spontaneous preterm delivery.
- 2022
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Ingår i: Clinical and translational medicine. - : Wiley. - 2001-1326. ; 12:9
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Tidskriftsartikel (refereegranskat)abstract
- Intrauterine infection and inflammation caused by microbial transfer from the vagina are believed to be important factors causing spontaneous preterm delivery (PTD). Multiple studies have examined the relationship between the cervicovaginal microbiome and spontaneous PTD with divergent results. Most studies have applied a DNA-based assessment, providing information on the microbial composition but not transcriptional activity. A transcriptomic approach was applied to investigate differences in the active vaginal microbiome and human transcriptome at midgestation between women delivering spontaneously preterm versus those delivering at term.Vaginal swabs were collected in women with a singleton pregnancy at 18 + 0 to 20 + 6 gestational weeks. For each case of spontaneous PTD (delivery<37 + 0weeks) two term controls were randomized (39 + 0 to 40 + 6weeks). Vaginal specimens were subject to sequencing of both human and microbial RNA. Microbial reads were taxonomically classified using Kraken2 and RefSeq as a reference. Statistical analyses were performed using DESeq2. GSEA and HUMAnN3 were used for pathway analyses.We found 17 human genes to be differentially expressed (false discovery rate, FDR<0.05) in the preterm group (n =48) compared to the term group (n =96). Gene expression of kallikrein-2 (KLK2), KLK3 and four isoforms of metallothioneins 1 (MT1s) was higher in the preterm group (FDR<0.05). We found 11 individual bacterial species to be differentially expressed (FDR<0.05), most with a low occurrence. No statistically significant differences in bacterial load, diversity or microbial community state types were found between the groups.In our mainly white population, primarily bacterial species of low occurrence were differentially expressed at midgestation in women who delivered preterm versus at term. However, the expression of specific human transcripts including KLK2, KLK3 and several isoforms of MT1s was higher in preterm cases. This is of interest, because these genes may be involved in critical inflammatory pathways associated with spontaneous PTD.
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