| 1. |
- Kuusela, Pihla, et al.
(author)
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Second trimester cervical length measurements with transvaginal ultrasound : a prospective observational agreement and reliability study
- 2020
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In: Acta Obstetricia et Gynecologica Scandinavica. - : John Wiley & Sons. - 0001-6349 .- 1600-0412. ; 99:11, s. 1476-1485
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Journal article (peer-reviewed)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.
(author)
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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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In: British Journal of Obstetrics and Gynecology. - : Wiley-Blackwell Publishing Inc.. - 1470-0328 .- 1471-0528. ; 128:2, s. 195-206
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Journal article (peer-reviewed)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. |
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| 4. |
- Kuusela, Pihla
(author)
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Ultrasound measurement of cervical length in the second trimester of pregnancy for prediction of preterm delivery
- 2019
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Doctoral thesis (other academic/artistic)abstract
- Abstract Background: Short cervical length is a risk factor for preterm delivery (PTD) and screening of cervical length using transvaginal ultrasound in the second trimester is a proposed method to find women at risk Aims: To examine the potential value of routine measurement of cervical length in a Swedish population of women with singleton pregnancies in the prediction of PTD. To estimate inter- and intra-observer agreement and reliability of cervical length measurements. Methods: Women at routine fetal scan examinations in the second trimester were recruited to a study measuring cervical length with transvaginal ultrasound. Assessments were performed by certified midwives. Women were recruited at two Swedish centers in the PILOT study (Paper I) and at seven Swedish centers in the CERVIX study (Paper II). In the PILOT study the results of the measurements were not blinded but in the CERVIX study they were. The cervix was measured once in the PILOT study and twice, at least two weeks apart, in the CERVIX study. The isthmus was measured separately in the CERVIX study. The REPRODUCIBILITY study (Paper III) forms part of the CERVIX study and consists of two studies: the LIVE study and the CLIPS study. In the LIVE study, seven pairs of midwives assessed cervical length in between 24 and 30 women each. In the CLIPS study, 16 trained examiners (raters) measured cervical length twice at least two months apart on 93 video clips. The midwives were blinded to each other´s results and in the CLIPS study also to their own previous results. Results: Paper I: In the PILOT study, cervical length was measured in 2122 women. Median cervical length at 16-23 gestational weeks (GW) was 39.0 mm and the prevalence of a short cervix (≤25 mm) was 0.5%. There was a significant association between cervical length and spontaneous PTD <34 GW. Paper II: The CERVIX study included 11 456 women. The prevalence of endocervical length ≤25 mm was 4.0% at 18-20 GW (Cx1) and 4.4% at 21-23 GW (Cx2). Isthmus was present in 23% at Cx1 and in 9% at Cx2. The discriminative ability of endocervical length was better in women with no isthmus than in women with isthmus and better at Cx2 than at Cx1. At Cx1, to predict spontaneous PTD at <33 GW the best cut-off point for endocervical length was ≤29 mm, which had a sensitivity of 43%, Area Under receiver operating characteristic Curve (AUC) of 0.68. The corresponding figure at Cx2 was ≤27 mm with AUC 0.76. Using the 27 mm cut-off at Cx2 identified 54% of spontaneous PTD before 33 gestational weeks with 35 false positive test results per one true positive and 449 women were screened to correctly identify one woman as being at risk. Paper III: For the best examiner pair in the LIVE study the mean difference between the two examiners’ measurements of endocervical length was 0.33 mm, the limits of agreement -4.06 to 4.72 mm, for the poorest examiner pair it was 0.73 mm and -11.7 to 13.2 mm, respectively. In the CLIPS study, the repeatability for the best rater was 3.9 mm and that of the poorest 9.6 mm (median 5.9 mm). Conclusions: In the second trimester short cervical length is a risk factor for spontaneous PTD - the shorter the cervix the higher the risk. At this point cervical length has a moderate ability to identify women at risk, the disciminative ability being higher to predict very early PTD (<30 GW) than PTD 34-37 GW. Inter-observer agreement and reliability of second trimester cervical length measurements differed substantially between examiner pairs in the LIVE study and so did intra-observer measurement error, repeatability and reliability between the examiners in the CLIPS study. Key words: Cervical length measurement, preterm delivery, second trimester of pregnancy, prospective study, cohort study, observational study, mass screening, reproducibility of results, inter-observer variation, intra-observer variation, data accuracy, quality control
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| 5. |
- Wennerholm, Ulla-Britt, 1948, et al.
(author)
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Progesterone, cerclage, pessary, or acetylsalicylic acid for prevention of preterm birth in singleton and multifetal pregnancies : A systematic review and meta-analyses
- 2023
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In: Frontiers in Medicine. - : Frontiers Media S.A.. - 2296-858X. ; 10
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Research review (peer-reviewed)abstract
- Background: Preterm birth is the leading cause of childhood mortality and morbidity. We aimed to provide a comprehensive systematic review on randomized controlled trials (RCTs) on progesterone, cerclage, pessary, and acetylsalicylic acid (ASA) to prevent preterm birth in asymptomatic women with singleton pregnancies defined as risk of preterm birth and multifetal pregnancies.Methods: Six databases (including PubMed, Embase, Medline, the Cochrane Library) were searched up to February 2022. RCTs published in English or Scandinavian languages were included through a consensus process. Abstracts and duplicates were excluded. The trials were critically appraised by pairs of reviewers. The Cochrane risk-of-bias tool was used for risk of bias assessment. Predefined outcomes including preterm birth, perinatal/neonatal/maternal mortality and morbidity, were pooled in meta-analyses using RevMan 5.4, stratified for high and low risk of bias trials. The certainty of evidence was assessed using the GRADE approach. The systematic review followed the PRISMA guideline.Results: The search identified 2,309 articles, of which 87 were included in the assessment: 71 original RCTs and 16 secondary publications with 23,886 women and 32,893 offspring. Conclusions were based solely on trials with low risk of bias (n = 50).Singleton pregnancies: Progesterone compared with placebo, reduced the risk of preterm birth < 37 gestational weeks: 26.8% vs. 30.2% (Risk Ratio [RR] 0.82 [95% Confidence Interval [CI] 0.71 to 0.95]) (high certainty of evidence, 14 trials) thereby reducing neonatal mortality and respiratory distress syndrome. Cerclage probably reduced the risk of preterm birth < 37 gestational weeks: 29.0% vs. 37.6% (RR 0.78 [95% CI 0.69 to 0.88]) (moderate certainty of evidence, four open trials). In addition, perinatal mortality may be reduced by cerclage. Pessary did not demonstrate any overall effect. ASA did not affect any outcome, but evidence was based on one underpowered study.Multifetal pregnancies: The effect of progesterone, cerclage, or pessary was minimal, if any. No study supported improved long-term outcome of the children.Conclusion: Progesterone and probably also cerclage have a protective effect against preterm birth in asymptomatic women with a singleton pregnancy at risk of preterm birth. Further trials of ASA are needed. Prevention of preterm birth requires screening programs to identify women at risk of preterm birth.
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| 6. |
- Wikström, Tove, et al.
(author)
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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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In: Acta Obstetricia et Gynecologica Scandinavica. - : John Wiley & Sons. - 0001-6349 .- 1600-0412. ; 100:9, s. 1644-1655
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Journal article (peer-reviewed)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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| 7. |
- Wikström, Tove, et al.
(author)
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Microbial and human transcriptome in vaginal fluid at midgestation: Association with spontaneous preterm delivery.
- 2022
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In: Clinical and translational medicine. - : Wiley. - 2001-1326. ; 12:9
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Journal article (peer-reviewed)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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