| 1. |
- Jacobsson, Bo, 1960, et al.
(author)
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Quantification of Ureaplasma urealyticum DNA in the amniotic fluid from patients in PTL and pPROM and its relation to inflammatory cytokine levels
- 2008
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In: Acta Obstet Gynecol Scand. - 1600-0412. ; , s. 1-8
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Journal article (peer-reviewed)abstract
- Objective. To study the effect of the amniotic fluid quantity of Ureaplasma urealyticum DNA on inflammatory response levels in women with preterm labor (PTL) and preterm prelabor rupture of membranes (pPROM). Design. A prospective multi-center follow up study. Setting. Sahlgrenska University Hospital, Goteborg, Sweden and Turku University Hospital, Turku, Finland. Sample. Eleven U. urealyticum positive samples obtained after transabdominal amniocenteses in 197 women presenting with PTL and pPROM. Methods. The U. urealyticum positive samples were analyzed with real-time polymerase chain reaction, using the Lightcycler instrument with primers specific for U. urealyticum 16 S rDNA. The amniotic fluid samples were analyzed for tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-1beta and IL-10 with enzyme-linked immunosorbent assays. Main outcome measures. Correlation between U. urealyticum DNA concentrations in the amniotic fluid and inflammatory cytokine levels. Results. The concentrations of U. urealyticum DNA varied between 0.024 and 934microg/mL. A significant correlation between U. urealyticum DNA and TNF-alpha level was observed. No correlation with the other cytokines was found. Women with PTLhad higher levels of U. urealyticum DNA and a different cytokine pattern than women with pPROM. Conclusions. U. urealyticum in the amniotic fluid induces an inflammatory reaction in a dose dependent manner and the quantity of U. urealyticum DNA is well correlated with the level of the inflammatory cytokine TNF-alpha.
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| 2. |
- Jacobsson, Bo, 1960, et al.
(author)
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Quantification of Ureaplasma urealyticum DNA in the amniotic fluid from patients in PTL and pPROM and its relation to inflammatory cytokine levels
- 2009
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In: Acta Obstet Gynecol Scand. ; 88:1, s. 63-70
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To study the effect of the amniotic fluid quantity of Ureaplasma urealyticum DNA on inflammatory response levels in women with preterm labor (PTL) and preterm prelabor rupture of membranes (pPROM). DESIGN: A prospective multi-center follow up study. SETTING: Sahlgrenska University Hospital, Goteborg, Sweden and Turku University Hospital, Turku, Finland. SAMPLE: Eleven U. urealyticum positive samples obtained after transabdominal amniocenteses in 197 women presenting with PTL and pPROM. METHODS: The U. urealyticum positive samples were analyzed with real-time polymerase chain reaction, using the Lightcycler instrument with primers specific for U. urealyticum 16 S rDNA. The amniotic fluid samples were analyzed for tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-1beta and IL-10 with enzyme-linked immunosorbent assays. MAIN OUTCOME MEASURES: Correlation between U. urealyticum DNA concentrations in the amniotic fluid and inflammatory cytokine levels. RESULTS: The concentrations of U. urealyticum DNA varied between 0.024 and 934 microg/mL. A significant correlation between U. urealyticum DNA and TNF-alpha level was observed. No correlation with the other cytokines was found. Women with PTLhad higher levels of U. urealyticum DNA and a different cytokine pattern than women with pPROM. CONCLUSIONS: U. urealyticum in the amniotic fluid induces an inflammatory reaction in a dose dependent manner and the quantity of U. urealyticum DNA is well correlated with the level of the inflammatory cytokine TNF-alpha.
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| 3. |
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| 4. |
- Morken, Nils-Halvdan, 1969, et al.
(author)
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Obstetric and neonatal outcome of pregnancies fathered by males on immunosuppression after solid organ transplantation.
- 2015
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In: American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. - : Elsevier BV. - 1600-6143. ; 15:6, s. 1666-73
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Journal article (peer-reviewed)abstract
- Immunosuppressive drugs may influence spermatogenesis, but little is known about outcome of pregnancies fathered by transplanted males. We estimated risk of adverse outcomes in pregnancies (with data after the first trimester) fathered by males that had undergone organ transplantation and were treated with immunosuppression. A population-based study, linking data from the Norwegian transplant registry and the Medical Birth Registry of Norway during 1967-2009 was designed. All Norwegian men undergoing solid organ transplantation were included. Odds ratios for major malformations, preeclampsia, preterm delivery (<37 weeks) and small-for-gestational-age were obtained using logistic regression. A total of 2463 transplanted males, fathering babies of 4614 deliveries before and 474 deliveries after transplantation were identified. The risk of preeclampsia was increased (AOR: 7.4, 95% CI: 1.1-51.4,) after transplantation compared to prior to transplantation. No increased risk was found for congenital malformations or other outcomes when compared with pregnancies before transplantation or with the general population (2 511 506 births). Our results indicate an increased risk of preeclampsia mediated through the transplanted and immunosuppressed father. Importantly, no increased risk was found for other adverse obstetric outcomes or malformations, which may reassure male transplant recipients planning to father children.
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| 5. |
- Morken, Nils-Halvdan, 1969, et al.
(author)
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Outcomes of preterm children according to type of delivery onset: a nationwide population-based study
- 2007
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In: Paediatric and Perinatal Epidemiology. - : Wiley. - 0269-5022 .- 1365-3016. ; 21:5, s. 458-464
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Journal article (peer-reviewed)abstract
- The objective of the study was to investigate whether spontaneous and iatrogenic preterm births are associated with different paediatric outcomes. A nationwide population-based study comprising 1 010 487 singletons used data from 1991 to 2001 from the Swedish Medical Birth Register and the Swedish Hospital Discharge Register. Intrauterine fetal deaths, unknown type of delivery onset and congenital malformations were excluded. Neonatal, perinatal and long-term neurological outcomes were studied. Spontaneous preterm births were compared with iatrogenic preterm births. Odds ratios (OR) and hazard ratios (HR) for outcome variables were obtained using the Mantel-Haenszel technique and Cox analyses respectively. Adjustments were made for gestational age at birth, maternal age, parity and smoking. The preterm population consisted of 34 215 (73.2%) spontaneous preterm infants and 12 511 (26.8%) iatrogenic preterm infants. Spontaneous preterm infants were at increased risk of cerebral palsy at gestational age 28-31 weeks (HR: 1.86 [95% CI: 1.12, 3.10]), and of sepsis at gestational age 32-33 weeks (HR: 1.58 [95% CI: 1.28, 1.96]). Other outcome variables were associated with iatrogenic preterm birth, especially respiratory and gastrointestinal diagnoses. In conclusion, spontaneous preterm birth and iatrogenic preterm birth are associated with different paediatric outcomes.
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| 6. |
- Morken, Nils-Halvdan, 1969, et al.
(author)
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Preterm birth in Sweden 1973-2001: rate, subgroups, and effect of changing patterns in multiple births, maternal age, and smoking
- 2005
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In: Acta Obstet Gynecol Scand. - : Wiley. ; 84:6, s. 558-565
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Journal article (peer-reviewed)abstract
- BACKGROUND: The objectives of this report are to evaluate changes in the preterm birth rate in Sweden 1973-2001. Furthermore, describe the proportion of spontaneous and indicated preterm births and assess risk factors for the subgroups of preterm birth during the period from 1991 to 2001. METHODS: A population-based register study of all births occurring in Sweden from 1973 to 2001 registered in the Swedish Medical Birth Register was designed. The analysis of subgroups was restricted to the period 1991-2001. Gestational age was calculated using last menstrual period and best estimate. Odds ratio for preterm birth related to risk factors was calculated for the subgroups' spontaneous and indicated preterm birth. RESULTS: After an increase in the beginning of the 1980s, the preterm birth rate has decreased from 6.3% in 1984 to 5.6% in 2001 (P < 0.0001). The proportion of multiple births born preterm of the total birth rate increased from 0.34% in 1973 to 0.71% in 2001 (P < 0.0001). Spontaneous preterm births account for 55.2% and iatrogenic preterm births for 20.2% of all preterm births. The strongest association with maternal smoking in early pregnancy was found at gestational age <28 weeks and spontaneous preterm birth [odds ratio (OR) smoking versus no smoking: 1.55, 95% confidence intervals (CI): 1.42-1.69]. The strongest association for maternal age was found between gestational age <28 weeks and indicated preterm birth (OR 5-year increase: 1.34, 95% CI: 1.21-1.47). CONCLUSIONS: The preterm birth rate in Sweden has decreased since the mid 1980s. The composition of different subtypes of preterm birth in a Scandinavian low-risk population seems to be similar to populations with higher incidence of preterm birth and perinatal infections.
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| 7. |
- Morken, Nils-Halvdan, 1969
(author)
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Public Health Aspects of Preterm Birth. Studies using Scandinavian population-based data
- 2008
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Doctoral thesis (other academic/artistic)abstract
- Background: Preterm birth is an unresolved serious global health problem. Research must be multi-disciplinary, with assessment of risk factors and causative agents at many levels of observation. Such an important level is the public health aspect of preterm birth. The general aim of this thesis was to describe, assess and explore public health aspects of preterm birth. Material and Methods: Scandinavian population-based data from the three Medical Birth Registers in Sweden, Denmark and Norway, as well as the Swedish Hospital Discharge Register were used. Preterm birth in Sweden during the Birth Register era from 1973 to 2001 was described, and subgroups of preterm birth during 1991-2001 was assessed. The association between spontaneous preterm birth and deviant fetal birth weight from the population mean was explored. We propose to use reference populations as a supplement in international comparison of baseline differences in preterm birth proportions and for time trend surveillance. The outcome of preterm born infants when comparing spontaneous preterm birth with iatrogenic preterm birth was examined. Models for prediction of spontaneous preterm birth <34 and <37 weeks were developed and validated in a test population by combining logistic regression and Bayesian methods. Results: (I) The proportion of preterm birth (<37 weeks) in Sweden decreased from 6.3% in 1984 to 5.6% in 2001 (<0.0001) and was evident among singleton births at 34-36 gestational weeks. The composition of preterm subgroups was similar with findings from populations with higher preterm birth proportions. (II) Associations between smaller than the population mean and spontaneous preterm birth were evident for all gestational age groups. The largest risk was found at 28-31 gestational weeks and birth weight <-3SD (OR: 13.3; 95%CI: 10.3-17.2). Spontaneous preterm infants born at 34-36 gestational weeks weighed 1-1.9 SD (OR: 1.1; 95%CI: 1.1-1.2) or 2-2.9 SD (OR: 1.6; 95%CI: 1.5-1.7) above the expected mean more often. (III) The national preterm delivery rate (<37 weeks) increased in Denmark from 5.3% to 6.1% (p<0.001) and in Norway from 6.0% to 6.4% (p=0.006), but remained unchanged in Sweden, during 1995-2004. In Denmark, the preterm delivery rate in the reference population (5.3% to 6.3%, p<0.001) and the spontaneous preterm delivery rate in the reference population (4.4% to 6.8%, p<0.001) increased significantly. No similar increase was evident in Norway. In Sweden, rates in the reference population remained stable. (IV) Spontaneous preterm infants were at increased risk of experiencing cerebral palsy at gestational age 28-31 weeks (HR: 1.86; 95%CI: 1.12-3.10) and sepsis at gestational age 32-33 weeks (HR: 1.58; 95%CI: 1.28-1.96). Other outcome variables were associated with iatrogenic preterm birth, in particular respiratory and gastrointestinal diagnoses. (V) Six prediction models were developed and the area under the receiver operator curve in the test population ranged from 0.77 (95%CI 0.76-0.77) to 0.59 (95%CI 0.57-0.61) for spontaneous preterm birth <37 weeks and from 0.80 (95%CI 0.79-0.81) to 0.64 (95%CI 0.62-0.67) for spontaneous preterm birth <34 weeks. For each delivery in the test population, the model that to the greatest extent utilized the available information was used, and total area under the receiver operator curve for spontaneous preterm birth <34 weeks (0.74, 95%CI 0.73-0.75) and <37 weeks (0.71, 95%CI 0.7-0.71) were calculated. Conclusions: The proportion of preterm birth in Sweden has decreased since the mid-eighties. Deviation of fetal birth weight from the expected mean is associated with spontaneous preterm delivery. Reference populations may prove to be a valuable supplement to assessments of national preterm delivery proportions in public health surveillance. Spontaneous preterm birth and iatrogenic preterm birth are associated with different paediatric outcomes. Spontaneous preterm birth can be predicted by using the proposed models, which could be applicable in clinical assessment of risk.
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| 8. |
- Morken, Nils-Halvdan, 1969, et al.
(author)
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Reference population for international comparisons and time trend surveillance of preterm delivery proportions in three countries
- 2008
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In: BMC Womens Health. - : Springer Science and Business Media LLC. - 1472-6874. ; 8
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Journal article (peer-reviewed)abstract
- BACKGROUND: International comparison and time trend surveillance of preterm delivery rates is complex. New techniques that could facilitate interpretation of such rates are needed. METHODS: We studied all live births and stillbirths (>or= 28 weeks gestation) registered in the medical birth registers in Sweden, Denmark and Norway from 1995 through 2004. Gestational age was determined by best estimate. A reference population of pregnant women was designed using the following criteria: 1) maternal age 20-35, 2) primiparity, 3) spontaneously conceived pregnancy, 4) singleton pregnancy and 5) mother born in the respective country. National preterm delivery rate, preterm delivery rate in the reference population and rate of spontaneous preterm delivery in the reference population were calculated for each country. RESULTS: The total national preterm delivery rate (< 37 completed gestational weeks), increased in both Denmark (5.3% to 6.1%, p < 0.001) and Norway (6.0% to 6.4%, p = 0.006), but remained unchanged in Sweden, during 1995-2004. In Denmark, the preterm delivery rate in the reference population (5.3% to 6.3%, p < 0.001) and the spontaneous preterm delivery rate in the reference population (4.4% to 6.8%, p < 0.001) increased significantly. No similar increase was evident in Norway. In Sweden, rates in the reference population remained stable. CONCLUSION: Reference populations can facilitate overview and thereby explanations for changing preterm delivery rates. The model also permits comparisons over time. This model may in its simplicity prove to be a valuable supplement to assessments of national preterm delivery rates for public health surveillance.
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| 9. |
- Morken, Nils-Halvdan, 1969, et al.
(author)
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Risk of spontaneous preterm delivery in a low-risk population: the impact of maternal febrile episodes, urinary tract infection, pneumonia and ear–nose–throat infections
- 2011
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In: European Journal of Obstetrics and Gynecology and Reproductive Biology. - : Elsevier BV. - 0301-2115. ; 159:2, s. 310-4
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Journal article (peer-reviewed)abstract
- Objective To assess the associations between maternal infections during pregnancy (i.e. ear–nose–throat infection, pneumonia, urinary tract infection, febrile episodes and influenza-like infection) and spontaneous preterm delivery (SPTD). Study design Prospective questionnaire data from the Norwegian Mother and Child Cohort (MoBa) study, including more than 100 000 pregnancies and, collected during 1999–2008, were used. Linked data from the Medical Birth Registry of Norway were added. SPTD occurring between gestational weeks 22 + 0 days and 36 + 6 days was the main outcome. Data were analysed in two steps because questionnaires (including information about occurrence of the various infections so far) were completed at different stages of pregnancy. Hazard ratios (HR) were obtained using Cox regression. Results The SPTD proportion was low in this cohort: 2.9% and 2.7% at the two analysis steps, respectively. After exclusions, 67 310 and 60 689 pregnancies, respectively, remained for the analyses. Ear–nose–throat infections occurring before week 17 were associated with an increased risk of SPTD in the first (HR: 1.27, 95% CI: 1.08–1.50) and second (HR: 1.26, 95% CI: 1.04–1.52) step of the analysis, but not if occurring later in pregnancy. None of the other maternal infections were associated with an increased risk of SPTD. Conclusion In this low-risk population, ear–nose–throat infection in early pregnancy was associated with an increased risk of SPTD. However, infectious morbidity in later pregnancy was not. Thus, the link between maternal infection and preterm delivery may vary in different populations and health care settings.
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| 10. |
- Morken, Nils-Halvdan, 1969, et al.
(author)
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Subgroups of preterm delivery in the Norwegian Mother and Child Cohort Study
- 2008
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In: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 1600-0412 .- 0001-6349. ; 87:12, s. 1374-7
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Journal article (peer-reviewed)abstract
- The preterm deliveries in the Norwegian Mother and Child Cohort (MoBa) study were divided into subgroups: spontaneous preterm delivery, iatrogenic preterm delivery, multiple pregnancies, congenital malformations and intrauterine fetal deaths (IUFD). Records were linked with the Medical Birth Registry of Norway in order to permit identification of the different subgroups. The first 53,711 included pregnancies in the MoBa study were analyzed. Spontaneous preterm delivery accounted for 42% and iatrogenic preterm delivery for 28% of all preterm deliveries. Other important contributors to preterm delivery were multiple pregnancies (16%), congenital malformations (8.6%) and IUFD (5.2%). In conclusion, the subgroup composition of the preterm population in the MoBa study is similar to previously published data regarding both different and similar populations and is well suited for future studies of this complex obstetric entity.
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| 11. |
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| 12. |
- Pennell, C. E., et al.
(author)
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Genetic epidemiologic studies of preterm birth: guidelines for research
- 2007
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In: Am J Obstet Gynecol. - 1097-6868. ; 196:2, s. 107-18
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Journal article (peer-reviewed)abstract
- Over the last decade, it has become increasingly apparent that the cause of preterm birth is multifactorial, involving both genetic and environmental factors. With the development of new technologies capable of probing the genome, exciting possibilities now present themselves to gain new insight into the mechanisms leading to preterm birth. This review aims to develop research guidelines for the conduct of genetic epidemiology studies of preterm birth with the expectation that this will ultimately facilitate the comparison of data sets between study cohorts, both nationally and internationally. Specifically, the 4 areas addressed in this review includes: (1) phenotypic criteria, (2) study design, (3) considerations in the selection of control populations, and (4) candidate gene selection. This article is the product of discussions initiated by the authors at the 3rd International Workshop on Biomarkers and Preterm Birth held at the University of California, Los Angeles, Los Angeles, CA, in March 2005.
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| 13. |
- Ryckman, Kelli K, et al.
(author)
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Maternal and fetal genetic associations of PTGER3 and PON1 with preterm birth.
- 2010
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In: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 5:2
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Journal article (peer-reviewed)abstract
- OBJECTIVE: The purpose of this study was to identify associations between maternal and fetal genetic variants in candidate genes and spontaneous preterm birth (PTB) in a Norwegian population and to determine the effect size of those associations that corroborate a previous study of PTB. METHODS: DNA from 434 mother-baby dyads (214 cases and 220 controls) collected from the Norwegian Mother and Child Cohort (MoBa) was examined for association between 1,430 single nucleotide polymorphisms in 143 genes and PTB. These results were compared to a previous study on European Americans (EA) from Centennial Women's Hospital in Nashville, TN, USA. Odds ratios for SNPs that corroborated the Cenntennial study were determined on the combined MoBa and Centennial studies. RESULTS: In maternal samples the strongest results that corroborated the Centennial study were in the prostaglandin E receptor 3 gene (PTGER3; rs977214) (combined genotype p = 3x10(-4)). The best model for rs977214 was the AG/GG genotypes relative to the AA genotype and resulted in an OR of 0.55 (95% CI = 0.37-0.82, p = 0.003), indicating a protective effect. In fetal samples the most significant association in the combined data was rs854552 in the paraoxonase 1 gene (PON1) (combined allele p = 8x10(-4)). The best model was the TT genotype relative to the CC/CT genotypes, and resulted in an OR of 1.32 (95% CI = 1.13-1.53, p = 4x10(-4)). CONCLUSIONS: These studies identify single locus associations with preterm birth for both maternal and fetal genotypes in two populations of European ancestry.
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