| 1. |
- Bacelis, Jonas, 1984, et al.
(författare)
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Literature-Informed Analysis of a Genome-Wide Association Study of Gestational Age in Norwegian Women and Children Suggests Involvement of Inflammatory Pathways
- 2016
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:8
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Tidskriftsartikel (refereegranskat)abstract
- Background Five-to-eighteen percent of pregnancies worldwide end in preterm birth, which is the major cause of neonatal death and morbidity. Approximately 30% of the variation in gestational age at birth can be attributed to genetic factors. Genome-wide association studies (GWAS) have not shown robust evidence of association with genomic loci yet. We separately investigated 1921 Norwegian mothers and 1199 children from pregnancies with spontaneous onset of delivery. Individuals were further divided based on the onset of delivery: initiated by labor or prelabor rupture of membranes. Genetic association with ultrasound- dated gestational age was evaluated using three genetic models and adaptive permutations. The top-ranked loci were tested for enrichment in 12 candidate gene-sets generated by text-mining PubMed abstracts containing pregnancy-related keywords. The six GWAS did not reveal significant associations, with the most extreme empirical p = 5.1 x 10(-7). The top loci from maternal GWAS with deliveries initiated by labor showed significant enrichment in 10 PubMed gene-sets, e.g., p = 0.001 and 0.005 for keywords "uterus" and "preterm" respectively. Enrichment signals were mainly caused by infection/inflammation-related genes TLR4, NFKB1, ABCA1, MMP9. Literature-informed analysis of top loci revealed further immunity genes: IL1A, IL1B, CAMP, TREM1, TFRC, NFKBIA, MEFV, IRF8, WNT5A. Our analyses support the role of inflammatory pathways in determining pregnancy duration and provide a list of 32 candidate genes for a follow-up work. We observed that the top regions from GWAS in mothers with labor-initiated deliveries significantly more often overlap with pregnancy-related genes than would be expected by chance, suggesting that increased sample size would benefit similar studies.
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| 2. |
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| 3. |
- Englund-Ögge, Linda, et al.
(författare)
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Meal frequency patterns and glycemic properties of maternal diet in relation to preterm delivery: Results from a large prospective cohort study
- 2017
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 12:3
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Tidskriftsartikel (refereegranskat)abstract
- Background Dietary habits are linked to high maternal glucose levels, associated with preterm delivery. The aim of this study was to examine the associations between meal frequency and glycemic properties of maternal diet in relation to preterm delivery. This prospective cohort study included 66,000 women from the Norwegian Mother and Child Cohort Study (MoBa). Meal frequency and food intake data were obtained from a validated food frequency questionnaire during mid-pregnancy. Principal component factor analysis was used with a data-driven approach, and three meal frequency patterns were identified: "snack meal", "main meal", and "evening meal". Pattern scores were ranked in quartiles. Glycemic index and glycemic load were estimated from table values. Intakes of carbohydrates, added sugar, and fiber were reported in grams per day and divided into quartiles. Gestational age was obtained from the Medical Birth Registry of Norway. Preterm delivery was defined as birth at <37 gestational weeks. A Cox regression model was used to assess associations with preterm delivery. After adjustments, the "main meal" pattern was associated with a reduced risk of preterm delivery, with hazard ratios (HRs) of 0.89 (95% confidence interval (CI): 0.80, 0.98) and 0.90 (95% CI: 0.81, 0.99) for the third and fourth quartiles, respectively, and p for trend of 0.028. This was mainly attributed to the group of women with BMI >= 25 kg/m(2), with HRs of 0.87 (95% CI: 0.79, 0.96) and 0.89 (95% CI: 0.80, 0.98) for the third and fourth quartiles, respectively, and p for trend of 0.010. There was no association between glycemic index, glycemic load, carbohydrates, added sugar, fiber, or the remaining meal frequency patterns and pre-term delivery. Regular consumption of main meals (breakfast, lunch, dinner) was associated with a lower risk of preterm delivery. Diet should be further studied as potential contributing factors for preterm delivery.
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| 4. |
- Ferrero, D. M., et al.
(författare)
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Cross-Country individual participant analysis of 4.1 million singleton births in 5 countries with very high human development index confirms known associations but provides no biologic explanation for 2/3 of all preterm births
- 2016
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:9
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Tidskriftsartikel (refereegranskat)abstract
- Background Preterm birth is the most common single cause of perinatal and infant mortality, affecting 15 million infants worldwide each year with global rates increasing. Understanding of risk factors remains poor, and preventive interventions have only limited benefit. Large differences exist in preterm birth rates across high income countries. We hypothesized that understanding the basis for these wide variations could lead to interventions that reduce preterm birth incidence in countries with high rates. We thus sought to assess the contributions of known risk factors for both spontaneous and provider-initiated preterm birth in selected high income countries, estimating also the potential impact of successful interventions due to advances in research, policy and public health, or clinical practice. Methods We analyzed individual patient-level data on 4.1 million singleton pregnancies from four countries with very high human development index (Czech Republic, New Zealand, Slovenia, Sweden) and one comparator U.S. state (California) to determine the specific contribution (adjusting for confounding effects) of 21 factors. Both individual and populationattributable preterm birth risks were determined, as were contributors to cross-country differences. We also assessed the ability to predict preterm birth given various sets of known risk factors. Findings Previous preterm birth and preeclampsia were the strongest individual risk factors of preterm birth in all datasets, with odds ratios of 4.6-6.0 and 2.8-5.7, respectively, for individual women having those characteristics. In contrast, on a population basis, nulliparity and male sex were the two risk factors with the highest impact on preterm birth rates, accounting for 25-50% and 11-16% of excess population attributable risk, respectively (p<0.001). The importance of nulliparity and male sex on population attributable risk was driven by high prevalence despite low odds ratios for individual women. More than 65% of the total aggregated risk of preterm birth within each country lacks a plausible biologic explanation, and 63% of difference between countries cannot be explained with known factors; thus, research is necessary to elucidate the underlying mechanisms of preterm birth and, hence, therapeutic intervention. Surprisingly, variation in prevalence of known risk factors accounted for less than 35% of the difference in preterm birth rates between countries. Known risk factors had an area under the curve of less than 0.7 in ROC analysis of preterm birth prediction within countries. These data suggest that other influences, as yet unidentified, are involved in preterm birth. Further research into biological mechanisms is warranted. Conclusions We have quantified the causes of variation in preterm birth rates among countries with very high human development index. The paucity of explicit and currently identified factors amenable to intervention illustrates the limited impact of changes possible through current clinical practice and policy interventions. Our research highlights the urgent need for research into underlying biological causes of preterm birth, which alone are likely to lead to innovative and efficacious interventions. © 2016 Ferrero et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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| 5. |
- Frier, Emily M, et al.
(författare)
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Consortium for the Study of Pregnancy Treatments (Co-OPT): An international birth cohort to study the effects of antenatal corticosteroids.
- 2023
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 18:3
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Tidskriftsartikel (refereegranskat)abstract
- Antenatal corticosteroids (ACS) are widely prescribed to improve outcomes following preterm birth. Significant knowledge gaps surround their safety, long-term effects, optimal timing and dosage. Almost half of women given ACS give birth outside the "therapeutic window" and have not delivered over 7 days later. Overtreatment with ACS is a concern, as evidence accumulates of risks of unnecessary ACS exposure.The Consortium for the Study of Pregnancy Treatments (Co-OPT) was established to address research questions surrounding safety of medications in pregnancy. We created an international birth cohort containing information on ACS exposure and pregnancy and neonatal outcomes by combining data from four national/provincial birth registers and one hospital database, and follow-up through linked population-level data from death registers and electronic health records.The Co-OPT ACS cohort contains 2.28 million pregnancies and babies, born in Finland, Iceland, Israel, Canada and Scotland, between 1990 and 2019. Births from 22 to 45 weeks' gestation were included; 92.9% were at term (≥ 37 completed weeks). 3.6% of babies were exposed to ACS (67.0% and 77.9% of singleton and multiple births before 34 weeks, respectively). Rates of ACS exposure increased across the study period. Of all ACS-exposed babies, 26.8% were born at term. Longitudinal childhood data were available for 1.64 million live births. Follow-up includes diagnoses of a range of physical and mental disorders from the Finnish Hospital Register, diagnoses of mental, behavioural, and neurodevelopmental disorders from the Icelandic Patient Registers, and preschool reviews from the Scottish Child Health Surveillance Programme. The Co-OPT ACS cohort is the largest international birth cohort to date with data on ACS exposure and maternal, perinatal and childhood outcomes. Its large scale will enable assessment of important rare outcomes such as perinatal mortality, and comprehensive evaluation of the short- and long-term safety and efficacy of ACS.
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| 6. |
- Hallingström, Maria, et al.
(författare)
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Mid-trimester amniotic fluid proteome’s association with spontaneous preterm delivery and gestational duration
- 2020
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203 .- 1932-6203. ; 15:5
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Tidskriftsartikel (refereegranskat)abstract
- Background Amniotic fluid is clinically accessible via amniocentesis and its protein composition may correspond to birth timing. Early changes in the amniotic fluid proteome could therefore be associated with the subsequent development of spontaneous preterm delivery. Objective The main objective of this study was to perform unbiased proteomics analysis of the association between mid-trimester amniotic fluid proteome and spontaneous preterm delivery and gestational duration, respectively. A secondary objective was to validate and replicate the findings by enzyme-linked immunosorbent assay using a second independent cohort. Methods Women undergoing a mid-trimester genetic amniocentesis at Sahlgrenska University Hospital/Östra between September 2008 and September 2011 were enrolled in this study, designed in three analytical stages; 1) an unbiased proteomic discovery phase using LC-MS analysis of 22 women with subsequent spontaneous preterm delivery (cases) and 37 women who delivered at term (controls), 2) a validation phase of proteins of interest identified in stage 1, and 3) a replication phase of the proteins that passed validation using a second independent cohort consisting of 20 cases and 40 matched controls. Results Nine proteins were nominally significantly associated with both spontaneous preterm delivery and gestational duration, after adjustment for gestational age at sampling, but none of the proteins were significant after correction for multiple testing. Several of these proteins have previously been described as being associated with spontaneous PTD etiology and six of them were thus validated using enzyme linked immunosorbent assay. Two of the proteins passed validation; Neutrophil gelatinase-associated lipocalin and plasminogen activator inhibitor 1, but the results could not be replicated in a second cohort. Conclusions Neutrophil gelatinase-associated lipocalin and Plasminogen activator inhibitor 1 are potential biomarkers of spontaneous preterm delivery and gestational duration but the findings could not be replicated. The negative findings are supported by the fact that none of the nine proteins from the exploratory phase were significant after correction for multiple testing.
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| 7. |
- Hallingström, Maria, et al.
(författare)
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Proteomic Analysis of Early Mid-Trimester Amniotic Fluid Does Not Predict Spontaneous Preterm Delivery
- 2016
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:5
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Tidskriftsartikel (refereegranskat)abstract
- Objective The aim of this study was to identify early proteomic biomarkers of spontaneous preterm delivery (PTD) in mid-trimester amniotic fluid from asymptomatic women. This is a case-cohort study. Amniotic fluid from mid-trimester genetic amniocentesis (14-19 weeks of gestation) was collected from 2008 to 2011. The analysis was conducted in 24 healthy women with subsequent spontaneous PTD (cases) and 40 randomly selected healthy women delivering at term (controls). An exploratory phase with proteomics analysis of pooled samples was followed by a verification phase with ELISA of individual case and control samples. The median (interquartile range (IQR: 25th; 75th percentiles) gestational age at delivery was 35+5 (33+6-36+6) weeks in women with spontaneous PTD and 40+0 (39+1-40+5) weeks in women who delivered at term. In the exploratory phase, the most pronounced differences were found in C-reactive protein (CRP) levels, that were approximately two-fold higher in the pooled case samples than in the pooled control samples. However, we could not verify these differences with ELISA. The median (25th; 75th IQR) CRP level was 95.2 ng/mL (64.3; 163.5) in women with spontaneous PTD and 86.0 ng/mL (51.2; 145.8) in women delivering at term (p = 0.37; t-test). Proteomic analysis with mass spectrometry of mid-trimester amniotic fluid suggests CRP as a potential marker of spontaneous preterm delivery, but this prognostic potential was not verified with ELISA.
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| 8. |
- Hornychova, Helena, et al.
(författare)
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Cervical human papillomavirus infection in women with preterm prelabor rupture of membranes.
- 2018
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 13:11
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Tidskriftsartikel (refereegranskat)abstract
- To evaluate the association between cervical human papillomavirus (HPV) infection at the time of admission and the presence of microbial invasion of the amniotic cavity (MIAC) and intra-amniotic inflammation (IAI) in women with preterm prelabor rupture of membranes (PPROM) and to determine the association between cervical HPV infection and short-term neonatal morbidity.One hundred women with singleton pregnancies complicated by PPROM between the gestational ages of 24+0 and 36+6 weeks were included in the study. The presence of HPV DNA was evaluated in scraped cervical cells using polymerase chain reaction (PCR). Amniotic fluid samples were obtained by transabdominal amniocentesis.The rate of cervical HPV infection in women with PPROM was 24%. The rates of MIAC and IAI were not different between women with cervical HPV infection and those without cervical HPV infection [MIAC: with HPV: 21% (5/24) vs. without HPV: 22% (17/76), p = 1.00; IAI: with HPV: 21% (5/24) vs. without HPV: 18% (14/76), p = 0.77]. There were no differences in the selected aspects of short-term neonatal morbidity between women with and without cervical HPV infection.In women with PPROM, the presence of cervical HPV infection at the time of admission is not related to a higher risk of intra-amniotic infection-related and inflammatory complications or worse short-term neonatal outcomes.
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| 9. |
- Kacerovsky, Marian, et al.
(författare)
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Cervical Gardnerella vaginalis in women with preterm prelabor rupture of membranes.
- 2021
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 16:1
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Tidskriftsartikel (refereegranskat)abstract
- To determine the association between microbial invasion of the amniotic cavity (MIAC) and/or intra-amniotic inflammation (IAI) and the cervical prevalence of Gardnerella vaginalis DNA in pregnancies with preterm prelabor rupture of membrane (PPROM).In total, 405 women with singleton pregnancies complicated with PPROM were included. Cervical fluid and amniotic fluid samples were collected at the time of admission. Bacterial and G. vaginalis DNA were assessed in the cervical fluid samples using quantitative PCR technique. Concentrations of interleukin-6 and MIAC were evaluated in the amniotic fluid samples. Loads of G. vaginalis DNA ≥ 1% of the total cervical bacterial DNA were used to define the cervical prevalence of G. vaginalis as abundant. Based on the MIAC and IAI, women were categorized into four groups: with intra-amniotic infection (both MIAC and IAI), with sterile IAI (IAI without MIAC), with MIAC without IAI, and without either MIAC or IAI.The presence of the abundant cervical G. vaginalis was related to MIAC (with: 65% vs. without: 44%; p = 0.0004) but not IAI (with: 52% vs. without: 48%; p = 0.70). Women with MIAC without IAI had the highest load of the cervical G. vaginalis DNA (median 2.0 × 104 copies DNA/mL) and the highest presence of abundant cervical G. vaginalis (73%).In women with PPROM, the presence of cervical G. vaginalis was associated with MIAC, mainly without the concurrent presence of IAI.
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| 10. |
- Modzelewska, Dominika, et al.
(författare)
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Changes in data management contribute to temporal variation in gestational duration distribution in the Swedish Medical Birth Registry
- 2020
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203 .- 1932-6203. ; 15:11
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Tidskriftsartikel (refereegranskat)abstract
- Multiple factors contribute to gestational duration variability. Understanding the sources of variability allows to design better association studies and assess public health measures. Here, we aimed to assess geographical and temporal changes in the determination of gestational duration and its reporting in Sweden between 1973 and 2012. Singleton live births between 1973 and 2012 were retrieved from the Swedish Medical Birth Register. Gestational duration trends in percentiles and rates of pre- and post-term deliveries were analyzed by plotting the values over time. Temporal changes in gestational duration based on ultrasound and last menstrual period (LMP) estimation methods were compared. Intervals between LMP date and LMP-based due date were analyzed to assess changes in expected gestational duration. In total, 3 940 577 pregnancies were included. From 1973 until 1985, the median of gestational duration estimated based on LMP or ultrasound decreased from 283 to 278 days, and remained stable until 2012. The distribution was relatively stable when ultrasound-based estimates were used. Until the mid-1990s, there was a higher incidence than expected of births occurring on every seventh gestational day from day 157 onward. On an average, these gestational durations were reported 1.8 times more often than adjacent durations. Until 1989, the most common expected gestational duration was 280 days, and thereafter, it was 279 days. The expected gestational duration varied from 279 to 281 days across different Swedish counties. During leap years, the expected gestational duration was one day longer. Consequently, leap years were also associated with significantly higher preterm and lower post-term delivery rates than non-leap years. Changes in data handling and obstetrical practices over the years contribute to gestational duration variation. The resulting increase in variability might reduce precision in association studies and hamper the assessment of public health measures aimed to improve pregnancy outcomes.
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