| 1. |
|
|
| 2. |
|
|
| 3. |
- Cobo, Teresa, et al.
(författare)
-
Intra-amniotic inflammation predicts microbial invasion of the amniotic cavity but not spontaneous preterm delivery in preterm prelabor membrane rupture.
- 2012
-
Ingår i: Acta obstetricia et gynecologica Scandinavica. - : Wiley. - 1600-0412 .- 0001-6349.
-
Tidskriftsartikel (refereegranskat)abstract
- Objective. To predict microbial invasion of the amniotic cavity (MIAC) and spontaneous preterm delivery within seven days using a panel of selected proteins from amniotic fluid in a Swedish population of preterm prelabor membrane rupture (PPROM). Design. Prospective cohort study. Setting. Evaluation of intra-amniotic inflammation in preterm premature rupture of membranes. Population. Sixty-six pregnant women with preterm prelabor membrane rupture at 22(+0-) 33(+6) weeks' gestational age. Methods. Twenty-seven amniotic fluid proteins were assayed by a multiple immunoassay. Main outcome measures. The intra-amniotic inflammatory response was evaluated according to the presence of MIAC and the risk of spontaneous preterm delivery within seven days. A prediction model was constructed using logistic regression. Results. The overall rates of MIAC and spontaneous preterm delivery within seven days were 20% and 50%, respectively. There was a higher inflammatory response in women with MIAC than without. Earlier gestational age at delivery and lower birthweight were observed in the presence of microbial invasion of the amniotic cavity. Amniotic fluid Interleukin (IL)-6 and IL-10 were the best predictors of MIAC in terms of sensitivity (69%), specificity (81%), positive predictive value (47%), negative predictive value (91%) and positive likelihood ratio of 3.6. There were no differences in intra-amniotic inflammatory response according to the risk of spontaneous preterm delivery within seven days. Conclusion. Amniotic fluid IL-6 and IL-10 are the best inflammatory biomarkers to predict MIAC in women with PPROM. Intra-amniotic inflammation does not predict the occurrence of spontaneous preterm delivery within seven days of PPROM.
|
|
| 4. |
- Hallingström, Maria, et al.
(författare)
-
The association between selected mid-trimester amniotic fluid candidate proteins and spontaneous preterm delivery
- 2020
-
Ingår i: Journal of Maternal-Fetal and Neonatal Medicine. - : Informa UK Limited. - 1476-7058 .- 1476-4954. ; 33:4, s. 583-592
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim of this study was to explore inflammatory response and identify early potential biomarkers in mid-trimester amniotic fluid associated with subsequent spontaneous preterm delivery (PTD). Methods: A cohort study was performed at Sahlgrenska University Hospital/Östra, Gothenburg, Sweden, between 2008 and 2010. Amniotic fluid was collected from consecutive women undergoing mid-trimester transabdominal genetic amniocentesis at 14–19 gestational weeks. Clinical data and delivery outcome variables were obtained from medical records. The analysis included 19 women with spontaneous PTD and 118 women who delivered at term. A panel of 26 candidate proteins was analyzed using Luminex xMAP technology. Candidate protein concentrations were analyzed with ANCOVA and adjusted for plate effects. Results: The median gestational age at delivery was 35 + 3 weeks in women with spontaneous PTD and 40 + 0 weeks in women who delivered at term. Nominally significantly lower amniotic fluid levels of adiponectin (PTD: median 130,695 pg/mL (IQR 71,852–199,414) vs term: median 185,329 pg/mL (IQR (135,815–290,532)), granulocyte-macrophage colony stimulating factor (PTD: median 137 pg/mL (IQR 74–156) vs term: median 176 pg/mL (IQR 111–262)), and macrophage migration inhibitory factor (PTD: median 3025 pg/mL (IQR 1885–3891) vs term: median 3400 pg/mL (IQR 2181–5231)) were observed in the spontaneous PTD group, compared with the term delivery group, after adjusting for plate effects. No significant differences remained after Bonferroni correction for multiple comparisons. Conclusions: Our results are important in the process of determining the etiology behind spontaneous PTD but due to the non-significance after Bonferroni correction, the results should be interpreted with caution. Further analyses of larger sample size will be required to determine whether these results are cogent and to examine whether microbial invasion of the amniotic cavity or intra-amniotic inflammation occurs in asymptomatic women in the mid-trimester with subsequent spontaneous PTD.
|
|
| 5. |
- Holst, Rose-Marie, 1946
(författare)
-
Cervical and intra-amniotic markers of preterm birth and infection
- 2009
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Abstract Background: Preterm delivery (PTD; < 37 gestational weeks), is one of the greatest unsolved obstetrical problems worldwide. As much as 80% of the perinatal mortality and 50% of the long-term neurological handicaps are associated with PTD. Spontaneous preterm birth (SPTD), i.e. preterm labor (PTL) or preterm prelabor rupture of membranes (PPROM) is responsible for 55% of PTD. Clinical and experimental evidence suggest that maternal infection and/or inflammation are centre stages in SPTD and the major risk factors for fetal injury. Several cytokines and chemokines play a central role in SPTD. However, in most cases the precise mechanistic pathway leading to SPTD remains unknown and good markers of prediction and therapies are few. Aim: To investigate if cervical and intra-amniotic proteins on their own and/or in combination with each other and/or with clinical characteristics could predict SPTD and intra-uterine infection/inflammation in women with singleton pregnancies in PTL. In particular the purpose was to investigate the predictive value of cervical markers (proteins or sonography) collected less invasively compared with amniotic fluid proteins collected via amniocentesis. Material and methods: A cohort of 134 women in PTL and 30 with PPROM with singleton pregnancies and gestational age less than 34 weeks were studied. Amniotic fluid (AF) was retrieved transabdominally from 107 patients in PTL and in 30 patients with PPROM. Cervical fluid (CF) was sampled from the external cervical os in all PTL women, but from none of the PPROM cases. Transvaginal sonography (TVS) assessing cervical length (CL) was performed in all patients. Polymerase chain reaction analyses for Ureaplasma urealyticum and Mycoplasma hominis and culture for aerobic and anaerobic bacteria were performed. Interleukin (IL)-6, IL-8, IL-18, monocyte chemotactic protein (MCP)-1, MCP-2, and MCP-3 were analyzed with enzyme-linked immunosorbent assay. The multiplex sandwich immunoassay, flowmetric Luminex xMAP (multiple analyte profiling) technology analyzed 27 specific proteins, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IL-17, IL-18, sIL-6rα, IFN-γ, TNF-α, TNF-β, MCP-1, TGF-β, MIP-1α, MIP-1β, MMP-9, TREM-1, BDNF, GM-CSF, NT-4, NT-3, sTNF RI, MIF and RANTES. Histological examinations of the placentas were performed in 42 cases in PTL and in 30 with PPROM. Maternal, antenatal and intrapartal variables were retrieved from medical records Results: Non-lacto-bacillus dominated flora was detected in CF in 25% (22/89) and 17% had microbial invasion of the amniotic cavity (MIAC) and 45% had intra-amniotic inflammation. High levels of IL-6 and IL-8 were associated with PTD ≤ 7 days from assay and ≤ 34 weeks of gestation. Cervical length assessed by TVS predicted intra-amniotic inflammation as well as PTD. Intra-amniotic levels of IL-6, IL-8, IL-18, MCP-1 and MCP-3 were all significantly higher in PTL cases with histological chorioamnionitis (HCA) whereas such relationship was not found in the PPROM group. Cervical IL-6 and IL-8 in PTL were associated HCA and an IL-8 value of 10.0 ng/mL was a strong predictor of HCA with sensitivity 100%, specificity 67%, positive predictive value 63%, and negative predicted value 100%. Several of the proteins analyzed in both AF and CF, by the xMAP technology, were associated with PTD ≤ 7 days from assay and with MIAC. Novel findings were that amniotic IL-17 and TREM1 and cervical IL-17, sIL-6r, BDNF, NT4, NT3, IL-4, IL-5, and RANTES were significantly higher in the women delivering within 7 days of assay. We found that cervical IL-17, sIL-6r, NT3, TNF-β, IL-4, and TREM1 were significantly associated with MIAC which has not previously been reported. A multivariate model combining amniotic macrophage inflammatory protein (MIP)-1β with cervical interferon (INF)-γ and MCP-1 predicted SPTD ≤ 7 days likelihood ratio (LR) 5.6 and area under the ROC-curve (AUC) 0.91 and a non-invasive multivariate model based on CL, cervical INF-γ, IL-6 and MCP-1 predicted SPTD ≤ 7 days with LR 4.7 and AUC 0.91. The best multivariate model predicting MIAC based on cervical IL-17 and MCP-1 had LR 6.0 and AUC 0.87. Conclusions: In the present studies, we have identified inflammatory markers in both cervical and amniotic fluid that together with cervical length as measured by transvaginal sonography can predict spontaneous preterm delivery, intraamniotic infection and/or inflammation and histological chorioamnionitis. It seems as the non-invasive route of sampling analytes can be used instead of the more commonly used invasive method of amniocentesis. Key words: Spontaneous preterm delivery, preterm labor, preterm prelabor rupture of membranes, intra-amniotic infection/inflammation, inflammatory proteins, histological chorioamnionitis, cervical and amniotic markers
|
|
| 6. |
- Holst, Rose-Marie, 1946, et al.
(författare)
-
Cervical length in women in preterm labor with intact membranes: relationship to intra-amniotic inflammation/microbial invasion, cervical inflammation and preterm delivery
- 2006
-
Ingår i: Ultrasound Obstet Gynecol. - : Wiley. - 0960-7692. ; 28:6, s. 768-74
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Intra-amniotic infection, diagnosed by microbial invasion of the amniotic cavity (MIAC) and/or the presence of intra-amniotic inflammation (IAI), is related to adverse perinatal outcome in women with preterm labor. Due to the subclinical nature of IAI, a correct diagnosis depends on amniocentesis, which is an invasive method not performed as a clinical routine. The aim of this study was to evaluate if cervical length measured by transvaginal sonography could assist in the identification of women at high risk for IAI. METHODS: Cervical length was assessed by transvaginal sonography in 87 women with singleton pregnancies in preterm labor (<34 weeks of gestation). Cervical (n=87) and amniotic (n=55) fluids were collected. Polymerase chain reactions for Ureaplasma urealyticum and Mycoplasma hominis, and culture for aerobic and anaerobic bacteria, were performed. Interleukin (IL)-6 and IL-8 were analyzed by enzyme-linked immunosorbent assay. RESULTS: IAI was present in 25/55 (45%) of the patients presenting with preterm labor who underwent amniocentesis. Women with IAI had a significantly shorter cervical length (median, 10 (range, 0-34) mm) than had those without IAI (median, 21 (range, 11-43) mm) (P<0.0001). Receiver-operating characteristics curve analysis showed that a cervical length (cut-off of 15 mm) predicted IAI (relative risk, 3.6; CI, 1.9-10.0) with a sensitivity of 72%, specificity of 83%, positive predictive value of 78% and negative predictive value of 78%. Cervical length was also significantly associated with preterm birth up to 7 days from sampling and at
|
|
| 7. |
- Holst, Rose-Marie, 1946, et al.
(författare)
-
Expression of cytokines and chemokines in cervical and amniotic fluid: Relationship to histological chorioamnionitis
- 2007
-
Ingår i: J Matern Fetal Neonatal Med. - : Informa UK Limited. ; 20:12, s. 885-893
-
Tidskriftsartikel (refereegranskat)abstract
- Objective. To correlate cervical and amniotic fluid cytokines and macrophage-related chemokines to the development of histological chorioamnionitis (HCA) in patients with preterm labor (PTL) and preterm prelabor rupture of the membranes (PPROM). Study design. Cervical and amniotic fluid interleukin (IL)-6, IL-8, IL-18, monocyte chemotactic protein (MCP)-1, MCP-2, and MCP-3 from pregnant women (at
|
|
| 8. |
- Holst, Rose-Marie, 1946, et al.
(författare)
-
Interleukin-6 and interleukin-8 in cervical fluid in a population of Swedish women in preterm labor: relationship to microbial invasion of the amniotic fluid, intra-amniotic inflammation, and preterm delivery.
- 2005
-
Ingår i: Acta obstetricia et gynecologica Scandinavica. - : Wiley. - 0001-6349. ; 84:6, s. 551-7
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Intrauterine infection and inflammation in women with preterm labor are related to adverse perinatal outcome. Due to its subclinical nature, a correct diagnosis depends on retrieval of amniotic fluid. Amniocentesis is, however, not performed as a clinical routine because of its invasiveness. Hypothetically, cytokines in the cervical fluid may represent an alternative diagnostic approach. The aim was to examine cervical interleukin (IL)-6 and IL-8 in relation to microbial invasion of the amniotic fluid, intra-amniotic inflammation, and preterm birth in women in preterm labor. METHODS: Women with singleton pregnancies in preterm labor (<34 weeks of gestation) and intact membranes were included. Cervical (n = 91) and amniotic fluids (n = 56) were collected. Polymerase chain reaction for Ureaplasma urealyticum and Mycoplasma hominis and culture for aerobic and anaerobic bacteria were performed. IL-6 and IL-8 were analyzed with enzyme-linked immunosorbent assay. RESULTS: Non-lactobacillus-dominated biota was detected in cervical secretion in 25% (22/89) and the presence of micro-organisms in the amniotic fluid in 16% (9/56) of the patients. The presence of U. urealyticum in the cervical fluid (21/46) was associated with significantly higher levels of IL-6 in the secretion. IL-6 and IL-8 were significantly higher in cervical fluid of women with intra-amniotic infection and inflammation and in women who delivered < or =7 days and/or before 34 weeks of gestation. Cervical IL-6 > or = 1.7 ng/ml was related to intra-amniotic inflammation (relative risk: 2.67; range: 1.50-4.74) and had a sensitivity, specificity, positive predictive value, and negative predictive value of 58, 83, 75, and 69%, respectively, in the identification of intra-amniotic inflammation. Similar data were obtained for IL-8 > or = 6.7 ng/ml. CONCLUSIONS: High levels of cervical IL-6 and IL-8 are moderately predictive of intrauterine infection/inflammation and preterm delivery.
|
|
| 9. |
- Holst, Rose-Marie, 1946, et al.
(författare)
-
Prediction of microbial invasion of the amniotic cavity in women with preterm labour: analysis of multiple proteins in amniotic and cervical fluids.
- 2011
-
Ingår i: BJOG : an international journal of obstetrics and gynaecology. - : Wiley. - 1471-0528 .- 1470-0328. ; 118:2, s. 240-249
-
Tidskriftsartikel (refereegranskat)abstract
- Objective Microbial invasion of the amniotic cavity is a major cause of preterm delivery and the diagnosis is dependent on invasive amniocentesis. The objective was to determine whether specific proteins in amniotic and cervical fluids alone, or in combination, could identify bacterial invasion. Design A prospective follow-up study. Population Women with singleton pregnancies presenting with preterm labour between 22 and 33weeks of gestation (n=89). Setting Sahlgrenska University Hospital, Gothenburg, Sweden. Methods Amniotic and cervical fluid was analysed with polymerase chain reaction for Mycoplasmas, and was cultured for aerobic and anaerobic bacteria. Twenty-seven proteins were analysed using multiplex technology. Individual levels of each protein were compared in order to find associations between different proteins and microbial invasion of the amniotic cavity. Predictive models based on multiple proteins were created using stepwise binary logistic regression. Main outcome measure The main outcome measure was microbial invasion of the amniotic cavity. Results Microbial invasion of the amniotic cavity was present in 17% (15/89) of the women. Concentration levels of several amniotic and cervical proteins were significantly higher in women with microbial invasion of the amniotic cavity. Three multivariate predictive models were found. The predictive power of the non-invasive model (73% sensitivity, 88% specificity, 55% positive predictive value, 94% negative predictive value) was as good as the invasive models. Area under the receiver operating characteristic (ROC) curve and likelihood ratio were 0.87 and 6.0, respectively. Conclusions Prediction of intra-amniotic infection using selected cervical proteins was equally good as prediction using the same proteins collected from amniotic fluid, or a combination of cervical and amniotic proteins.
|
|
| 10. |
- Holst, Rose-Marie, 1946, et al.
(författare)
-
Prediction of spontaneous preterm delivery in women with preterm labor: analysis of multiple proteins in amniotic and cervical fluids
- 2009
-
Ingår i: Obstet Gynecol. ; 114:2 Pt 1, s. 268-77
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To analyze whether specific proteins in amniotic and cervical fluids, alone or in combination with risk factors, can identify women in preterm labor with intact membranes who will deliver spontaneously within 7 days of sampling. METHODS: In a cohort of 89 women in preterm labor, amniotic and cervical fluids were collected between 22 and 33 weeks of gestation. Twenty-seven proteins were analyzed simultaneously using multiplex technology. Individual levels of each protein were compared and calculations performed to find associations among different proteins, background variables, and spontaneous preterm delivery within 7 days of sampling. The area under the curve (AUC) was calculated using receiver operating characteristic curve analysis, and prediction models were created based on stepwise logistic regression. RESULTS: We found two multivariable models that predicted spontaneous preterm delivery better than any single variable. One combined multivariable prediction model was based on amniotic macrophage inflammatory protein-1beta, cervical interferon-gamma, and monocyte chemotactic protein-1. This model predicted outcome with 91% sensitivity, 84% specificity, 78% positive predictive value, and 94% negative predictive value, with a likelihood ratio of 5.6 and AUC of 0.91. An alternative, noninvasive model based on cervical length, cervical interferon-gamma, interleukin-6, and monocyte chemotactic protein-1 predicted delivery within 7 days with 85% sensitivity, 82% specificity, 74% positive predictive value, and 90% negative predictive value, with a likelihood ratio of 4.7 and AUC of 0.91. CONCLUSION: A combination of proteins from amniotic fluid and cervical fluid or cervical length can help determine which women will deliver preterm. LEVEL OF EVIDENCE: II.
|
|
