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1.
Ned Tijdschr Geneeskd ; 1642020 10 14.
Article in Dutch | MEDLINE | ID: mdl-33331723

ABSTRACT

A circular zone of hair loss was noted in a two-weeks old male baby, born prematurely. A painful and hyperemic caput succedaneum was diagnosed postpartum. The finding was diagnosed as halo scalp ring, caused by hypoxic-ischaemic tissue damage at the edge of the caput succedaneum, resulting in temporary hair loss.


Subject(s)
Alopecia/etiology , Birth Injuries/complications , Craniocerebral Trauma/complications , Infant, Premature , Humans , Infant, Newborn , Male , Scalp/pathology
2.
BJOG ; 119(10): 1211-21, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22712829

ABSTRACT

OBJECTIVE: The aim was to examine the effects of low to moderate maternal alcohol consumption and binge drinking in early pregnancy on children's attention at 5 years of age. DESIGN: Prospective follow-up study. SETTING: Neuropsychological testing in four Danish cities 2003-2008. POPULATION: A cohort of 1628 women and their children sampled from the Danish National Birth Cohort. METHODS: Participants were sampled based on maternal alcohol consumption during pregnancy. At 5 years of age, the children were tested with the recently developed Test of Everyday Attention for Children at Five (TEACh-5). Parental education, maternal IQ, maternal smoking in pregnancy, the child's age at testing, gender, and tester were considered core confounding factors, whereas the full model also controlled the following potential confounding factors: maternal binge drinking or low to moderate alcohol consumption, age, body mass index (BMI), parity, home environment, postnatal smoking in the home, child's health status, and indicators for hearing and vision impairments. MAIN OUTCOME MEASURES: TEACh-5 attention scores. RESULTS: There were no significant effects on test performance in children of mothers drinking up to 8 drinks per week compared with children of mothers who abstained, but there was a significant association between maternal consumption of 9 or more drinks per week and risk of a low overall attention score (OR 3.50, 95% CI 1.15-10.68). No consistent or significant associations were observed between binge drinking and attention test scores. CONCLUSIONS: The findings suggest an effect of maternal consumption of 9 or more drinks per week on attention functions in children, but the study detected no effects of lower levels of maternal consumption and no consistent effects of maternal binge drinking.


Subject(s)
Alcohol Drinking/psychology , Attention , Prenatal Exposure Delayed Effects/epidemiology , Adult , Alcohol Drinking/epidemiology , Attention Deficit Disorder with Hyperactivity/epidemiology , Child, Preschool , Denmark/epidemiology , Educational Status , Ethanol/poisoning , Female , Humans , Intelligence/physiology , Male , Neuropsychological Tests , Pregnancy , Pregnancy Trimester, First , Pregnancy Trimester, Second , Prenatal Exposure Delayed Effects/chemically induced , Prospective Studies
3.
BJOG ; 119(7): 866-73, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22530716

ABSTRACT

OBJECTIVE: To analyse whether specific proteins in maternal serum and cervical length, alone or in combination, can predict the likelihood that women with intact membranes with threatened preterm labour will deliver spontaneously within 7 days of sampling. DESIGN: Cohort study. SETTING: Sahlgrenska University Hospital, Gothenburg, Sweden. POPULATION: Women at between 22 and 33 weeks of gestation with threatened preterm labour (n = 142) admitted to the Sahlgrenska University Hospital, Gothenburg, Sweden, in 1995-2005. METHODS: Maternal serum was tested for 27 proteins using multiplex xMAP technology. Individual levels of each protein were compared, and calculations were performed to investigate potential associations between different proteins, cervical length and spontaneous preterm delivery. Receiver operating characteristic curves were used to find the best cut-off values for continuous variables in relation to spontaneous preterm delivery within 7 days of sampling. Prediction models were created based on a stepwise logistic regression using binary variables. MAIN OUTCOME MEASURE: Spontaneous preterm delivery within 7 days. RESULTS: In order to determine the best prediction model, we analysed models of serum proteins alone, cervical length alone, and the combination of serum proteins and cervical length. We found one multivariable combined model through the data analysis that more accurately predicted spontaneous preterm delivery within 7 days. This model was based on serum interleukin-10 (IL-10) levels, serum RANTES levels and cervical length (sensitivity 74%, specificity 87%, positive predictive value 76%, negative predictive value 86%, likelihood ratio 5.8 and area under the curve 0.88). CONCLUSIONS: A combination of maternal serum proteins and cervical length constituted the best prediction model, and would help determine whether women with threatened preterm labour are likely to deliver within 7 days of measurement.


Subject(s)
Blood Proteins/metabolism , Cervical Length Measurement , Decision Support Techniques , Premature Birth/diagnosis , Adult , Biomarkers/blood , Chemokine CCL5/blood , Female , Humans , Interleukin-10/blood , Logistic Models , Multivariate Analysis , Obstetric Labor, Premature/blood , Pregnancy , Premature Birth/blood , Prospective Studies , ROC Curve , Sensitivity and Specificity
4.
J Epidemiol Community Health ; 65(6): 497-502, 2011 Jun.
Article in English | MEDLINE | ID: mdl-20584728

ABSTRACT

OBJECTIVES: To assess the risk of autism spectrum disorders (ASD) in children born after assisted conception compared with children born after natural conception. DESIGN: Population-based follow-up study. SETTING: All children born alive in Denmark 1995-2003. PARTICIPANTS: 588,967 children born in Denmark from January 1995 to December 2003. Assisted conception was defined as in vitro fertilisation (IVF) with or without intracytoplasmic sperm injection and ovulation induction (OI) with or without subsequent insemination. Children exposed to IVF or OI were identified in the IVF Register and in the Danish Drug Prescription Register. MAIN OUTCOME MEASURES: A diagnosis of ASD in the Danish Psychiatric Central Register. RESULTS: 33,139 (5.6%) of all children born in Denmark in 1995-2003 resulted from assisted conception, 225 of whom (0.68%) had a diagnosis of ASD. Of the 555,828 children born in this period after natural conception, 3394 (0.61%) had a diagnosis of ASD. The follow-up time was 4-13 years (median 9 years). In crude analyses, children born after assisted conception had an increased risk of a diagnosis of ASD: crude hazard rate ratio (HRR) 1.25 (95% CI 1.09 to 1.43). In analyses adjusting for maternal age, educational level, parity, smoking, birth weight and multiplicity, the risk disappeared: adjusted HRR 1.13. (95% CI 0.97 to 1.31). However, subgroup analyses that suggest possible associations in women who received follicle stimulating hormone indicate the need for further study. DISCUSSION: This population-based follow-up study found no risk of ASD in children born after assisted conception.


Subject(s)
Child Development Disorders, Pervasive/etiology , Reproductive Techniques, Assisted/adverse effects , Adult , Child , Child Development Disorders, Pervasive/epidemiology , Child, Preschool , Cohort Studies , Denmark/epidemiology , Female , Follow-Up Studies , Humans , Male , Risk Assessment , Young Adult
5.
BJOG ; 118(2): 240-9, 2011 Jan.
Article in English | MEDLINE | ID: mdl-21054762

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 33 weeks 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.


Subject(s)
Amniotic Fluid/microbiology , Bacteria/isolation & purification , Cervix Uteri/chemistry , Obstetric Labor, Premature/microbiology , Pregnancy Complications, Infectious/diagnosis , Proteins/metabolism , Adult , Body Fluids/chemistry , Early Diagnosis , Female , Follow-Up Studies , Humans , Obstetric Labor, Premature/diagnosis , Pregnancy , Prenatal Diagnosis/methods , Prospective Studies , Young Adult
6.
Hum Reprod ; 25(8): 2115-23, 2010 Aug.
Article in English | MEDLINE | ID: mdl-20554642

ABSTRACT

BACKGROUND: This paper assesses the risk of cerebral palsy (CP) in children born after assisted conception compared with children born after natural conception (NC). METHODS: This population based follow-up study included all 588,967 children born in Denmark from 1995 to 2003. Assisted conception was defined as IVF, with or without ICSI, and ovulation induction (OI), with or without subsequent insemination. RESULTS: There were 33 139 (5.6%) children born in Denmark from 1995 to 2003 as a result of assisted conception and through to June 2009, 1146 (0.19%) children received a CP diagnosis. Children born after assisted conception had an increased risk of a CP diagnosis, crude hazard rate ratio (HRR) 1.90 (95% CI: 1.57-2.31) compared with NC children. Divided into IVF and OI children compared with NC children, the risk was HRR 2.34 (95% CI: 1.81-3.01) and HRR 1.55 (95% CI: 1.17-2.06), respectively. When we included the intermediate factors multiplicity and gestational age in multivariate models, the risk of CP in assisted conception disappeared. In general, children with CP born after assisted conception had similar CP subtypes and co-morbidities as children with CP born after NC. CONCLUSION: The risk of CP is increased after both IVF and OI. The increased risk of CP in children born after assisted conception, and in particular IVF, is strongly associated with the high proportion of multiplicity and preterm delivery in these pregnancies. A more widespread use of single embryo transfer warrants consideration to enhance the long-term health of children born after IVF.


Subject(s)
Cerebral Palsy/epidemiology , Fertilization in Vitro , Infant, Premature , Multiple Birth Offspring , Adolescent , Adult , Child , Cohort Studies , Denmark/epidemiology , Female , Follow-Up Studies , Gestational Age , Humans , Infant, Newborn , Prevalence , Risk Assessment , Risk Factors
7.
Gynecol Obstet Invest ; 70(1): 40-6, 2010.
Article in English | MEDLINE | ID: mdl-20160447

ABSTRACT

BACKGROUND/AIMS: To examine the relationship of biological mediators (cytokines, stress hormones), psychosocial, obstetric history, and demographic factors in the early prediction of preterm birth (PTB) using a comprehensive logistic regression model incorporating diverse risk factors. METHODS: In this prospective case-control study, maternal serum biomarkers were quantified at 9-23 weeks' gestation in 60 women delivering at <37 weeks compared to 123 women delivering at term. Biomarker data were combined with maternal sociodemographic factors and stress data into regression models encompassing 22 preterm risk factors and 1st-order interactions. RESULTS: Among individual biomarkers, we found that macrophage migration inhibitory factor (MIF), interleukin-10, C-reactive protein (CRP), and tumor necrosis factor-alpha were statistically significant predictors of PTB at all cutoff levels tested (75th, 85th, and 90th percentiles). We fit multifactor models for PTB prediction at each biomarker cutoff. Our best models revealed that MIF, CRP, risk-taking behavior, and low educational attainment were consistent predictors of PTB at all biomarker cutoffs. The 75th percentile cutoff yielded the best predicting model with an area under the ROC curve of 0.808 (95% CI 0.743-0.874). CONCLUSION: Our comprehensive models highlight the prominence of behavioral risk factors for PTB and point to MIF as a possible psychobiological mediator.


Subject(s)
Corticotropin-Releasing Hormone/blood , Cytokines/blood , Hypothalamo-Hypophyseal System/immunology , Pituitary-Adrenal System/immunology , Premature Birth , Adolescent , Adult , C-Reactive Protein/immunology , C-Reactive Protein/metabolism , Corticotropin-Releasing Hormone/immunology , Cytokines/immunology , Female , Humans , Hydrocortisone/blood , Hydrocortisone/immunology , Infant, Newborn , Inflammation/epidemiology , Inflammation/immunology , Inflammation/psychology , Interleukin-10/blood , Interleukin-10/immunology , Interleukin-6/blood , Interleukin-6/immunology , Intramolecular Oxidoreductases/blood , Intramolecular Oxidoreductases/immunology , Macrophage Migration-Inhibitory Factors/blood , Macrophage Migration-Inhibitory Factors/immunology , Neuroimmunomodulation/immunology , Pregnancy , Premature Birth/epidemiology , Premature Birth/immunology , Premature Birth/psychology , Psychology , Risk Factors , Tumor Necrosis Factor-alpha/blood , Tumor Necrosis Factor-alpha/immunology , Young Adult
8.
Hum Reprod ; 24(9): 2332-40, 2009 Sep.
Article in English | MEDLINE | ID: mdl-19454590

ABSTRACT

BACKGROUND: An increasing number of children are born after assisted conception and in surveillance programmes information on mode of conception is often achieved via maternal self-report. We assessed the validity of self-reported assisted conception in The Danish National Birth Cohort (DNBC), a prospective pregnancy cohort. Here, the term assisted conception refers to IVF, ICSI, ovulation induction and insemination. METHODS: We compared self-reported assisted conception in the DNBC to corresponding data from Danish national registers; the IVF Register and Danish Drug Prescription Register, providing method of conception in the entire population. In the DNBC, 101,042 women accepted the invitation in early pregnancy from 1996 to 2002. Our final study population comprised 88,151 DNBC women aged 20 years and older who participated in the first DNBC interview with a pregnancy resulting in a live born child. RESULTS: In the DNBC, assisted conception was reported with a sensitivity of 83% and positive predictive value of 88%. Misclassification was largely explained by ambiguous phrasing of the DNBC interview question and interview skip patterns. Women with false negative reporting were more often multipara (P < 0.001) and older (P = 0.027 for IVF/ICSI and P = 0.002 for ovulation induction). The risk ratio (RR) for being born preterm in IVF/ICSI children was lower for children identified via the DNBC, RR 3.61 (95% confidence interval (CI) 3.31-3.94), than the IVF Register, RR 4.36 (95% CI 4.02-4.74). CONCLUSIONS: There was a high positive predictive value of self-reported assisted conception in the DNBC, but the structure of the DNBC interview represented a problem and misclassification could introduce bias.


Subject(s)
Reproductive Techniques, Assisted/statistics & numerical data , Self Disclosure , Adult , Cohort Studies , Denmark/epidemiology , False Negative Reactions , False Positive Reactions , Female , Fertilization in Vitro/statistics & numerical data , Humans , Interviews as Topic/standards , Predictive Value of Tests , Pregnancy , Prospective Studies , Sensitivity and Specificity , Sperm Injections, Intracytoplasmic/statistics & numerical data , Surveys and Questionnaires/standards
9.
BJOG ; 115(12): 1518-28, 2008 Nov.
Article in English | MEDLINE | ID: mdl-19035988

ABSTRACT

OBJECTIVE: To investigate the association of asphyxia-related conditions (reducing blood flow or blood oxygen levels in the fetus) with spastic cerebral palsy (CP) considering different gestational age groups and the timing of risk. DESIGN: Population-based case-control study. SETTING: Danish Cerebral Palsy Register in eastern Denmark and Danish Medical Birth Register. POPULATION OR SAMPLE: 271 singletons with spastic CP and 217 singleton controls, frequency matched by gestational age group, born 1982-1990 in eastern Denmark. METHODS: Data were abstracted from medical records, and a priori asphyxia-related conditions and other risk factors were selected for analysis. Each factor was classified according to the time at which it was likely to first be present. MAIN OUTCOME MEASURES: Spastic CP. RESULTS: Placental and cord complications accounted for the majority of asphyxia conditions. In multivariate analysis, placental infarction was significantly associated with a four-fold increased risk for spastic quadriplegia and cord around the neck was significantly associated with a three-fold increased risk for spastic CP overall. The combination of placental infarction and being small for gestational age (SGA) afforded an especially high risk for spastic quadriplegia. Placental and cord complications were present in 21% of cases and 12% of controls. CONCLUSIONS: The risk for spastic quadriplegia from placental infarction may be linked in some cases with abnormal fetal growth (17% of all children with spastic quadriplegia and 3% of control children both had an infarction and were SGA) -- suggesting an aetiologic pathway that encompasses both factors. The risk for spastic CP from cord around the neck is not accounted for by other prepartum or intrapartum factors we examined. Considering the relative timing of risk factors provides a useful framework for studies of CP aetiology.


Subject(s)
Asphyxia Neonatorum/etiology , Cerebral Palsy/etiology , Fetal Diseases , Placenta Diseases , Adolescent , Adult , Case-Control Studies , Denmark , Female , Gestational Age , Humans , Infant, Newborn , Infant, Small for Gestational Age/physiology , Obstetric Labor Complications , Pregnancy , Quadriplegia/etiology , Registries , Risk Factors , Umbilical Cord , Young Adult
10.
J Reprod Immunol ; 77(2): 152-60, 2008 Apr.
Article in English | MEDLINE | ID: mdl-17692390

ABSTRACT

Few studies have assessed longitudinal changes in circulating cytokine levels during normal pregnancy. We have examined the natural history of maternal plasma cytokines from early- to mid-pregnancy in a large, longitudinal cohort. Multiplex flow cytometry was used to measure interleukin (IL)-2, IL-6, IL-12, tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma and granulocyte-macrophage colony-stimulating factor (GM-CSF) in early- (median [IQR]: 8.5 weeks [7.1, 10.0]) and mid-pregnancy (25.0 [24.1, 26.1]) from 1274 Danish women delivering singleton term infants. GM-CSF decreased from early- to mid-pregnancy (median percent change [95% CI]: -51.3% [-59.1%, -41.8%]), while increases were observed in IL-6 (24.3% [4.6%, 43.9%]), IL-12 (21.3% [8.9%, 35.7%]) and IFN-gamma (131.7% [100.2%, 171.6%]); IL-2 (-2.8% [-11.5%, 0.0%]) and TNF-alpha (0% [-5.9%, 25.6%]) remained stable. Positive correlations were found between all cytokines, both in early- and mid-pregnancy (all p<0.001). Early- and mid-pregnancy levels were rank-correlated for IL-2, IL-12, TNF-alpha and GM-CSF, but not IL-6 and IFN-gamma; these correlations were generally weaker than correlations between different cytokines at a single time point in pregnancy. Women with a pre-pregnancy BMI <18.5 had reduced levels of IFN-gamma and GM-CSF compared to women in other BMI categories, while women aged >or=35 years had elevated IL-2, IL-6, TNF-alpha and IFN-gamma. Early-pregnancy levels of TNF-alpha were higher in women with a prior preterm delivery. Cytokine levels were not associated with gravidity. In conclusion, cytokines were detected in plasma during early- and mid-pregnancy, with IL-6, IL-12, IFN-gamma and GM-CSF concentrations varying over pregnancy. Concentrations may depend on BMI, maternal age and prior preterm delivery.


Subject(s)
Cytokines/blood , Cytokines/immunology , Pregnancy/blood , Adult , Age Factors , Body Mass Index , Denmark , Female , Gestational Age , Granulocyte-Macrophage Colony-Stimulating Factor/blood , Granulocyte-Macrophage Colony-Stimulating Factor/immunology , Humans , Interferon-gamma/blood , Interferon-gamma/immunology , Interleukin-12/blood , Interleukin-12/immunology , Interleukin-2/blood , Interleukin-2/immunology , Interleukin-6/blood , Interleukin-6/immunology , Obstetric Labor, Premature/immunology , Pregnancy Trimester, First/immunology , Time Factors , Tumor Necrosis Factor-alpha/blood , Tumor Necrosis Factor-alpha/immunology
11.
J Reprod Immunol ; 77(2): 179-85, 2008 Apr.
Article in English | MEDLINE | ID: mdl-17850880

ABSTRACT

INTRODUCTION: Mice disrupted for the interleukin (IL)-18 gene appear more disposed to preterm delivery (PTD) induced by inflammation. A synergy between IL-18 and IL-12 has been suggested. The objective of this study was to investigate a possible relation between human maternal serum levels of IL-18, IL-12 and spontaneous PTD. MATERIALS AND METHODS: A cohort of 93 consecutive women with symptoms of threatening PTD on admission was enrolled at the delivery ward, Aarhus University Hospital, Denmark. MEASURES: Serum IL-18 and IL-12 measured using Luminex xMAP technology. Endpoint: PTD before 34 weeks gestation. RESULTS: Pregnant women admitted with symptoms of threatening PTD and delivering before 34 weeks of gestation had significantly lower levels of IL-18 compared to women delivering at or after 34 weeks of gestation (medians: 14.5 versus 26.6 pg/ml; p=0.035). IL-12 levels were not different in women delivering before or after 34 weeks of gestation. Patients having low IL-18 (below the 25-percentile) and high IL-12 (above the 75-percentile) had a twofold increase in risk of delivering before 34 weeks of gestation (RR 2.1 [1.7-2.6]). CONCLUSION: Results from this study indicate, that low serum IL-18 level could be associated with PTD in women with symptoms of PTD. A possible interaction between IL-18 and IL-12 was found, as the risk of delivering before 34 weeks is increased with the combination of low IL-18 and high IL-12, but further studies are warranted to investigate these interleukins and their possible role in PTD.


Subject(s)
Interleukin-12/blood , Interleukin-18/blood , Obstetric Labor, Premature/immunology , Adolescent , Adult , Denmark , Female , Gestational Age , Humans , Interleukin-12/immunology , Interleukin-18/immunology , Obstetric Labor, Premature/blood , Pregnancy , Risk Factors
12.
Placenta ; 28(8-9): 946-50, 2007.
Article in English | MEDLINE | ID: mdl-17517432

ABSTRACT

OBJECTIVE: The objective of this study is to examine TNF-alpha and its soluble and membrane bound receptors in fetal membranes derived from blacks and whites in response to in vitro infectious stimulus, and the balance between TNF-alpha and the receptors. Fetal membranes collected from black and white women at term were maintained in an organ explant system and stimulated with lipopolysaccharide (LPS). TNF-alpha, soluble TNF receptors (sTNFR1 and sTNFR2) in culture media and membrane bound TNF receptors (TNFR1 and TNFR2) in tissue homogenates were measured. Molar ratio (TNF/sTNFR) was calculated between LPS stimulated and unstimulated (controls) cultures in both races. TNF-alpha was increased in both races after LPS stimulation and showed no difference between races (p=0.7). LPS decreased sTNFR1 in blacks, but increased in whites, showing a significant difference between races (p=0.001). In blacks sTNFR2 also decreased and increased in whites, but the results were not significant between races (p=0.4). Both TNFR1 and TNFR2 were increased in blacks after LPS stimulation whereas no such changes were seen in whites compared to controls that were also significant between races. After LPS stimulation TNF-alpha bioavailability was increased in blacks with a drop in soluble receptors and with an increase in membrane receptors. This was not evident in whites because in whites soluble receptors were increased with no change in membrane receptors. Our data demonstrated that LPS stimulation results in a molar ratio switch favoring TNF-alpha biofunction in blacks, but not in whites.


Subject(s)
Black or African American , Tumor Necrosis Factor-alpha , Biological Availability , Humans , Receptors, Tumor Necrosis Factor, Type I , Receptors, Tumor Necrosis Factor, Type II , Tumor Necrosis Factor-alpha/metabolism
13.
Ann Hum Genet ; 71(Pt 5): 586-600, 2007 Sep.
Article in English | MEDLINE | ID: mdl-17346257

ABSTRACT

Preterm birth (PTB) is a significant neonatal health problem that is more common in African-Americans (AA) than in European-Americans (EA). Part of this disparity is likely to result from the differing genetic architectures of EA and AA. To begin assessing the role of these differences, patterns of genetic variation in two previously proposed candidate genes, encoding interleukin 6 (IL6) and its receptor (IL6R), were analyzed in mothers and fetuses from 496 EA birth-events (149 cases and 347 controls) and 397 birth-events in AA (76 cases and 321 controls). IL-6 levels in amniotic fluid (AF) samples were determined in a subset of these pregnancies. Case-control comparisons revealed a single SNP in IL6R associated with PTB (p=0.04 for allelic and p=0.05 for genotype association). In addition, all of the SNPs studied showed significant frequency differences between AA and EA in at least one comparison, significantly in excess of that expected from general population databases. Higher IL-6 concentrations were associated with the IL6 SNP -661 in EA preterm samples (p=0.0056), and this result seems to be driven by microbial invasion of the amniotic cavity, indicating a gene by infection interaction. These findings indicate that, as a function of IL6 genotype, EA and AA women respond differently to infection with respect to their expression of IL-6. Our data support differential genetic control of levels of IL-6 in amniotic fluid between EA and AA.


Subject(s)
Amniotic Fluid/metabolism , Ethnicity/genetics , Interleukin-6/genetics , Premature Birth/genetics , Proteins/metabolism , Receptors, Interleukin-6/genetics , Adult , Black or African American/genetics , Female , Humans , Pregnancy , Premature Birth/ethnology , White People/genetics
15.
Ugeskr Laeger ; 163(38): 5183-8, 2001 Sep 17.
Article in Danish | MEDLINE | ID: mdl-11577524

ABSTRACT

INTRODUCTION: Urinary incontinence is a common problem for adult women, and the need for assessment and treatment of incontinence is expected to increase in the future. The aim of this study was to elucidate the general practitioners' (GPs) knowledge about and attitude to women with urinary incontinence. METHODS: A questionnaire was posted to 1700 randomly selected GPs in 1998 and 1999. RESULTS: A total of 1071 (63%) GPs responded at least once. Five hundred (29%) returned the questionnaire both years. About 50% expressed a positive interest in the management of urinary incontinence. Only 24% felt that their knowledge was sufficient to manage incontinence. About 50% and 66% of the GPs would probably refer a patient with stress incontinence or urge incontinence to a specialist. The GPs' proposals for assessment and treatment were mainly consistent with good clinical practice. There were only minor changes in knowledge and attitude from 1998 to 1999. DISCUSSION: GPs' interest in urinary incontinence is moderate and management is characterised by a high referral rate to a specialist. Most GPs. consider their knowledge to be inadequate. There is need for education to ensure sufficient knowledge and to change the attitude, so that first-line assessment and treatment of urinary incontinence is carried out in general practice.


Subject(s)
Attitude of Health Personnel , Clinical Competence , Family Practice/standards , Physicians, Family/psychology , Urinary Incontinence/diagnosis , Urinary Incontinence/therapy , Adult , Denmark , Female , Humans , Male , Middle Aged , Physicians, Family/standards , Practice Patterns, Physicians' , Referral and Consultation/statistics & numerical data , Surveys and Questionnaires , Urinary Incontinence, Stress/diagnosis , Urinary Incontinence, Stress/therapy , Women's Health
16.
Paediatr Perinat Epidemiol ; 15 Suppl 2: 90-103, 2001 Jul.
Article in English | MEDLINE | ID: mdl-11520403

ABSTRACT

Fetal and neonatal mortality and morbidity rates are strongly associated with gestational age for delivery: the risk for poor outcome increases as gestational age decreases. Attempts to predict preterm delivery (PTD, spontaneous delivery before 37 weeks' gestation) have been largely unsuccessful, and rates of PTD have not improved in recent decades. More recently, the reported associations between infections in pregnancy and PTD suggest preventive initiatives that could be taken. The overall objective of the current study is to assess whether specific markers of infection (primarily interleukin (IL) 1beta, tumour necrosis factor (TNF) alpha, IL-6, and IL-10) obtained from maternal blood during pregnancy, alone or in combination with other risk factors for PTD, permit identification of women at risk for spontaneous PTD. To achieve this objective, data are obtained from two Danish prospective cohort studies involving serial collection of maternal blood samples, newborn cord blood samples, and relevant confounders and other risk factors for PTD. The first study consists of a completed Danish regional cohort of 3000 pregnant women enrolled in a study of microbiological causes of PTD, upon which a nested case-control study of PTD in 84 cases and 400 controls has been performed. The second study is a nested case-control study of 675 PTD cases (equally divided into three gestational age categories of 24-29 weeks' gestation, 30-33 weeks' gestation, and 34-36 weeks' gestation) and 675 controls drawn from the ongoing Danish National Birth Cohort study of 100 000 pregnant women enrolled during 1997-2001. The second study will provide the opportunity to refine and retest hypotheses from the first study, as well as to explore new hypotheses. Our preliminary work suggests that a single predictive marker effectively accounting for a large proportion of PTD is unlikely to be found. Rather, a search for multiple markers indicative of the multifactorial aetiology of PTD is likely to be more successful. Knowledge gained from the proposed studies will be implemented in a third, clinical intervention study against PTD. The first phase of the clinical intervention study will be to establish a risk-assessment model based on the "best" combination of biological/biochemical measures and other factors associated with PTD in order to identify pregnant women at very high risk of PTD. The second phase will be to apply an intervention model of tailored obstetric care to the very high-risk pregnant women for PTD identified in phase one. The intervention will be carried out against each specific risk factor associated with PTD identified for the individual. The aim is to reduce the risk for PTD attributed to the combination of risk factors included in the clinical intervention study.


Subject(s)
Obstetric Labor, Premature/etiology , Adult , Biomarkers/blood , Case-Control Studies , Cohort Studies , Cytokines/blood , Denmark , Female , Gestational Age , Humans , Infant, Low Birth Weight , Infant, Newborn , Interleukins/blood , Obstetric Labor, Premature/blood , Pregnancy , Tumor Necrosis Factor-alpha/metabolism , Ultrasonography, Prenatal , Vaginal Smears
17.
J Clin Endocrinol Metab ; 86(6): 2544-52, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11397853

ABSTRACT

Increased CRH secretion by the placenta of pregnant women has been associated with preterm birth. Certain indices of risk, both medical and psychosocial in nature, have been linked to preterm delivery. Levels of total, bound, and free CRH, CRH-binding protein (CRH-BP), and cortisol were measured prospectively in a large sample of pregnant Danish women who delivered preterm and term infants. Measures of maternal serum hormones were taken at 7--23 and 27--37 weeks gestation and, for those who delivered at term, at 37--43 weeks gestation. At 7--23 weeks gestation, maternal levels of total CRH (P = 0.01), bound CRH (P = 0.03), and CRH-BP (P = 0.01) were higher in the preterm than in the term group. At 27--37 weeks gestation, levels of total CRH (P < 0.0001), bound CRH (P < 0.0001), free CRH (P < 0.0001), and cortisol (P < 0.0001) were all higher in the preterm than the term group, whereas levels of CRH-BP (P < 0.0001) were lower in the preterm than in the term group. The best medical and behavioral factors associated with preterm delivery were, respectively, previous preterm delivery (P < 0.0001) and engagement in certain risk-taking behaviors (P = 0.008). The positive relations between preterm delivery and various adverse medical and socioeconomic variables with increases in placental secretion of CRH suggest that the latter may participate in the pathophysiology of preterm delivery.


Subject(s)
Carrier Proteins/blood , Corticotropin-Releasing Hormone/blood , Hydrocortisone/blood , Obstetric Labor, Premature/blood , Adult , Female , Gestational Age , Humans , Medical Records , Obstetric Labor, Premature/psychology , Pregnancy , Psychology , Reference Values , Risk Factors , Risk-Taking , Socioeconomic Factors
18.
Am J Obstet Gynecol ; 184(3): 427-33, 2001 Feb.
Article in English | MEDLINE | ID: mdl-11228498

ABSTRACT

OBJECTIVE: We studied the relationship between group B streptococcal colonization and preterm delivery. STUDY DESIGN: In this prospective study at a single hospital in Odense, Denmark, cervicovaginal cultures were obtained at < or = 24 weeks' gestation from all the women, at delivery from women with preterm deliveries, and from a random sample of women delivering at term. RESULTS: In 2846 singleton births, there was no significant association between group B streptococcal colonization at

Subject(s)
Anti-Bacterial Agents/therapeutic use , Obstetric Labor, Premature/microbiology , Pregnancy Complications, Infectious/microbiology , Streptococcal Infections/microbiology , Streptococcus agalactiae/isolation & purification , Adult , Case-Control Studies , Cervix Uteri/microbiology , Cohort Studies , Denmark , Female , Humans , Infant, Low Birth Weight , Infant, Newborn , Infant, Premature , Latex Fixation Tests , Multivariate Analysis , Pregnancy , Pregnancy Complications, Infectious/drug therapy , Statistics, Nonparametric , Streptococcal Infections/drug therapy , Surveys and Questionnaires
19.
Eur J Clin Microbiol Infect Dis ; 20(1): 65-7, 2001 Jan.
Article in English | MEDLINE | ID: mdl-11245329

ABSTRACT

In a nested case-control study, the occurrence of Ureaplasma urealyticum in cervical specimens from 84 women with idiopathic preterm delivery and from 400 women delivering at term was investigated. The two potential risk factors for preterm delivery, colonization with Ureaplasma urealyticum and bacterial vaginosis, were found to be interdependent variables. The association between these factors and preterm delivery was assessed by regression analysis. Neither colonization with Ureaplasma urealyticum (odds ratio [OR] 0.7, 95% confidence interval [CI] 0.4-1.2) nor bacterial vaginosis (OR 0.8, 95% CI 0.3-1.8) was associated with preterm delivery. In women who delivered preterm, biovar 2 was found significantly more often in those with the clinical diagnosis of bacterial vaginosis (43%) than in those without (5%) (OR 15, 95% CI 1.2-209).


Subject(s)
Obstetric Labor, Premature/microbiology , Pregnancy Complications, Infectious/microbiology , Ureaplasma Infections/complications , Ureaplasma urealyticum/isolation & purification , Vaginosis, Bacterial/complications , Birth Weight , Case-Control Studies , Delivery, Obstetric , Female , Humans , Odds Ratio , Pregnancy , Pregnancy Outcome , Regression Analysis , Risk Factors , Ureaplasma Infections/diagnosis , Ureaplasma urealyticum/classification , Vaginosis, Bacterial/diagnosis
20.
Differentiation ; 66(1): 49-59, 2000 Aug.
Article in English | MEDLINE | ID: mdl-10997592

ABSTRACT

Fetal antigen 1 (FA1) is a circulating EGF multidomain glycoprotein. FA1 and its membrane-associated precursor is defined by the mRNAs referred to as delta-like (dlk), preadipocyte factor 1 (pref-1) or zona glomerulosa-specific factor (ZOG). Using a polyclonal antibody recognising both forms, the localisation of FA1/dlk was analysed in embryonic and fetal tissues between week 5 to 25 of gestation and related to germinal origin and development. FA1 was observed in endodermally derived hepatocytes, glandular cells of the pancreas anlage, and in respiratory epithelial cells. FA1 was also present in mesodermally derived cells of the renal proximal tubules, adrenal cortex, Leydig and Hilus cells of the testes and ovaries, fetal chondroblasts, and skeletal myotubes. Ectodermally derived neuro- and adenohypophysial cells, cells in the floor of the 3rd ventricle and plexus choroideus were also FA1 positive. The number of cells expressing FA1 decreased during fetal development where the expression became restricted to specific functional cells. Epidermis, gut epithelium, gall bladder, blood cells, spleen, thyroid gland, salivary glands, and smooth muscle cells were FA1 negative. Analysis of extra-embryonic tissues from normal and pathological pregnancies revealed FA1 in stromal cells surrounding the blood islands of the yolk sac as well as in placental fibroblasts where the expression was most pronounced in diploid, androgenic complete hydatidiform moles. However, as measured by ELISA, the circulating maternal FA1 levels in complete moles were not different from normal pregnancies. The results presented suggest that FA1 is a growth and/or differentiation factor extensively expressed in immature cells and down-regulated during fetal development. FA1 down-regulation was associated with a shift in the subcellular localisation indicating differential post-translational/post-transcriptional modifications during fetal development. FA1 may be a new marker of cellular subtypes with a regenerative potential and of specific cells with endocrine or neuroendocrine functions.


Subject(s)
Embryo, Mammalian/blood supply , Embryo, Mammalian/metabolism , Endocrine System/metabolism , Glycoproteins/metabolism , Placental Circulation , Regeneration , Biomarkers/analysis , Biomarkers/blood , Ectoderm/metabolism , Embryo, Mammalian/chemistry , Embryo, Mammalian/cytology , Endoderm/metabolism , Female , Fetus/blood supply , Fetus/chemistry , Fetus/cytology , Fetus/metabolism , Glycoproteins/analysis , Glycoproteins/blood , Humans , Immunohistochemistry , Mesoderm/metabolism , Molecular Sequence Data , Placenta/blood supply , Placenta/chemistry , Placenta/cytology , Placenta/metabolism , Pregnancy
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