Maternal and foetal outcomes in pregnant systemic lupus erythematosus patients: an incident cohort from a stable referral population followed during 1990-2010.

OBJECTIVES: To assess the impact of systemic lupus erythematosus (SLE) on pregnancy outcome in a cohort of incident pregnant lupus patients referred to a Danish university hospital during 1990-2010. METHOD: All pregnant lupus patients were referred to the university hospital from a stable referral area with approximately 1.4 million inhabitants. Eighty-four pregnancies in 39 women were registered using the Danish National Registry and retrospective reviewing of medical records, laboratory results, and midwifery records from the Department of Rheumatology, the Department of Obstetrics and Gynaecology, and possible other departments. Data were compared to 29 059 births during 2005-2010, covering all births from the referral area. RESULTS: The 84 SLE pregnancies resulted in 62 live births. SLE flares developed in 46.4%, pre-eclampsia in 8.3%, and HELLP syndrome in 4.8% of cases. Significantly higher rates of premature delivery (p=0.0032), caesarean section (p=0.015), hypertension (p=0.025), and intrauterine growth retardation (IUGR) (p=0.003) were found. Disease activity significantly (p=0.021) increased the risk of prematurity threefold. Antiphospholipid antibody (aPL) presence significantly (p=0.002) increased the risk of spontaneous abortion threefold. Two babies died after extreme preterm birth. Two had neonatal lupus syndrome (NLS) and one had congenital heart block (CHB). Birth weight and length were significantly lower in the SLE cohort. An unexpectedly high number of cardiac septum defects (9.7%) were observed. CONCLUSIONS: From a stable referral area, an incident cohort of SLE pregnancies were mostly successful, but maternal and foetal complications were observed in one-half and one-third of cases, respectively. Outcome risk factors were identified. A possible new observation is a high frequency of cardiac septum defects.

Randomised trial of cervical cerclage, with and without occlusion, for the prevention of preterm birth in women suspected for cervical insufficiency.

OBJECTIVE: To evaluate the effect of cerclage, with and without cervical occlusion. DESIGN: Multicentre, stratified, randomised controlled trial. SETTING: Hospital-based multicentre study with 18 tertiary centres from nine countries. POPULATION: Women with a history of cervical insufficiency (prophylactic trial) and women with a short cervix (therapeutic trial) were recruited from August 2006 to August 2011. METHODS: A centralised telephone randomisation service with a computer system was used to randomise women to cervical cerclage with or without cervical occlusion. Only the analyst performing the interim analyses was blinded. MAIN OUTCOME MEASURES: The take-home baby rate (number of infants discharged alive from the hospital), gestational age at delivery, and the number of days in the neonatal intensive care unit (NICU). RESULTS: Women (n = 309) were stratified into the prophylactic trial (n = 213) or the therapeutic trial (n = 96). The trial stopped early due to slow recruitment and an interim analysis showing no benefit of occlusion. Final analysis comprised 197 women in the prophylactic trial and 87 women in the therapeutic trial. No added effect of cervical occlusion was found in terms of the take-home baby rate in the prophylactic trial (92 versus 90%, RR 1.03, 95% CI 0.94-1.12) or in the therapeutic trial (81 versus 85%, RR 0.96, 95% CI 0.79-1.16). No effect of cervical occlusion was found in terms of gestational age at delivery and number of days the neonate spent in the NICU. Cervical occlusion was associated with no harm. CONCLUSIONS: Cervical occlusion with cerclage had no significant additional effect.

Could a cervical occlusion suture be effective at improving perinatal outcome?

Cervical weakness and infection have long been regarded as major causes of preterm birth. Cervical cerclage has been used extensively to reduce the risk of preterm birth arising as a result of cervical weakness, but increasing evidence suggests that the cervix plays more than just a mechanical role. Immunological function of the cervix and mucus plug is thought to be important in minimising the ingress of microbes, which can lead to chorioamnionitis and rupture of the amniotic membranes. In this review, we examine the background of traditional cervical cerclage and introduce the concept of the occlusion suture and its potential benefit in reducing the risk of recurrent preterm prelabour rupture of membranes.

Cervical occlusion in women with cervical insufficiency: protocol for a randomised, controlled trial with cerclage, with and without cervical occlusion.

OBJECTIVE: To evaluate the effect of double cerclage compared with a single cerclage. DESIGN: Randomised, controlled multicentre trial. SETTING: Ten different countries are participating with both secondary and tertiary centres. The countries participating are Denmark, Sweden, Germany, United Kingdom, Spain, South Africa, Australia and India. This gives both a broad spectrum of diversity global and local. We expect a total of 242 women enrolled per year. POPULATION: Prophylactic study: 1. History of cervical incompetence/insufficiency. (Delivery 15 to <36 weeks.) 2. Congenital short cervix (secondary to maternal administration of diethyl stilbestrol) or traumatic/surgical damage rendering the vaginal approach difficult (e.g. conisation). 3. Cervical suture applied in previous pregnancy, successful outcome. 4. Previous failed cerclage. Therapeutic study: 5. Secondary cerclage: Short cervix, without the membranes being exposed to the vagina. 6. Tertiary cerclage: Short cervix, membranes exposed to the vagina. Observational study: Eligible women who refuse to be randomised will participate in an observational study. 7. Repeat/requested cervical occlusion. METHODS: The women will be randomised between a single (vaginal or abdominal) and a double cerclage. The cervical cerclage (McDonald or Shirodkar) as well as the abdominal suture will be performed with the same material and technique normally used by the participating department. Those randomised to the double cerclage will have their external os closed with a continuous nylon 2-0/3-0 suture, in addition to the standard single cerclage. Local guidelines concerning antibiotics, Heparin, bed rest, tocolytics etc. are followed and recorded in the follow-up form. MAIN OUTCOME MEASURES: Primary endpoint is take home baby rate. The secondary endpoints are gestational age at delivery, incidence of preterm birth (<34+0 days) and number of days in neonatal unit.

An in vitro study of antibacterial properties of the cervical mucus plug in pregnancy.

OBJECTIVE: To evaluate whether cervical mucus plugs are antibacterial in vitro. STUDY DESIGN: Cervical mucus plugs from 56 healthy women in labor were studied by 2 different antimicrobial assays: (1) analysis of the inhibition by the cervical mucus plug of several gram-positive and gram-negative bacteria by overlaying the cervical mucus plug onto an agar plate with imbedded bacteria, and (2) determination of the antibacterial property of the cervical mucus plug material by radial diffusion assay with group B Streptococcus and Escherichia coli. RESULTS: In the agar overlay assay, there was complete inhibition of clinical isolates of Staphylococcus saprophyticus, E coli, and Pseudomonas aeruginosa and patient-variable partial-to-complete inhibition of Enterococcus faecium, Staphylococcus aureus, Streptococcus pyogenes, and Streptococcus agalactiae. In the radial diffusion assay, cervical mucus plugs had activity toward group B Streptococcus equivalent to 0.075 microg/mL of gentamicin and toward E coli equivalent to 0.5 microg/mL of gentamicin. CONCLUSION: A low-molecular substance with antibacterial activity in the cervical mucus plug may protect the fetus against ascending infections.

[The value of vaginal swabs]. / Vaerdien af vaginalpodninger.

INTRODUCTION: The use of culture of vaginal secretions by physicians and their use of microscopy of vaginal secretions were assessed. METHODS: The study was conducted partly as a registration of all microbiological requests and reports from the Department of Clinical Microbiology in a selected period, and partly as a questionnaire sent to all general practitioners (GPs) and specialists in obstetrics and gynaecology in the county of Arhus. RESULTS: In only 19% of 1,354 vaginal swabs received in a month could the findings lead to a specific antimicrobial treatment; 48% of these cases could be diagnosed by microscopy of vaginal secretions alone. Sixty-four per cent of the physicians returned the questionnaire. Half of the specialists and 60% of the GPs performed microscopy. Twenty-five per cent of the physicians treated patients solely on the basis of clinical symptoms. DISCUSSION: General culture of vaginal secretions has a limited clinical value. The diagnosis in patients complaining of vaginal discharge can often be made by microscopy. There is, however, a need for training GPs in microscopy, as well as specialists.

Proteoglycans and hyaluronan in human fetal membranes.

OBJECTIVE: The aim of this study was to describe the distributions of major extracellular matrix components, such as proteoglycans, collagen and hyaluronan, in the fetal membranes at term. STUDY DESIGN: Fetal membranes were obtained from elective cesarean deliveries at term. Guanidinium extracts were analyzed for proteoglycans with alcian blue precipitation, sodium dodecyl sulfate- polyacrylamide gel electrophoresis, and Western blotting and for hyaluronan with a radioimmunoassay. Collagen was measured by estimating hydroxyproline content. Tissue sections were immunostained for decorin and biglycan and stained for hyaluronan with a biotin-labeled hyaluronan-binding protein. RESULTS: The fetal membranes contained predominantly smaller proteoglycans, such as biglycan and decorin. The amnion consisted of typical fibrous connective tissue with a high concentration of collagen. The amnion was dominated by decorin located in close connection with the collagen fibrils. The chorion was composed of a fibroblastic part containing collagen and decorin and a trophoblastic part mainly containing biglycan. In addition, large amounts of hyaluronan were found, especially in the amnion and in the decidual cell layers. CONCLUSION: The distributions of proteoglycans, collagen, and hyaluronan in human fetal membranes may explain the biomechanical properties of this tissue. We suggest that changes in the relative proportions of these extracellular molecules are crucial for the proposed maturation process in the fetal membranes during the last weeks of pregnancy.

Antibacterial properties of human amnion and chorion in vitro.

OBJECTIVE: The purpose of the present study was to explore the direct effects of amnion and chorion on bacterial growth in vitro including the antibacterial spectrum. Chorioamniotic membranes were obtained under sterile conditions from 13 healthy women undergoing elective cesarean section at term. Likewise, chorioamniotic membranes were obtained from 10 healthy women with spontaneous vaginal delivery at term. Five strains of Hemolytic streptococci group B (GBS) were tested and one clinical isolate of the following species or bacterial groups: Hemolytic streptococcus group A, Staphylococcus aureus, Staphylococcus saprophyticus, Enterococcus faecalis, Escherichia coli, Pseudomonas aeruginosa, Acinetobacter calcoaceticus and Lactobacillus species. Bacteriological media included (1) blood-agar medium; (2) a transparent agar medium for submerged cultures; and (3) a nutrient broth medium. RESULTS: An inhibitory effect of fetal membranes against a range of bacteria was found. Consistent results were obtained in experiments with cultures on agar and cultures suspended in agar (membranes from eight women in both studies). In experiments with liquid cultures (seven women) only chorion showed a marginal inhibitory effect. All strains were inhibited, but the most pronounced inhibition was obtained for streptococcus group A, S. aureus and S. saprophyticus by both chorion and amnion. CONCLUSION: This study demonstrated an inhibitory effect of the fetal membranes on a diverse panel of bacteria

[Life-threatening puerperal sepsis caused by group A streptococci]. / Livstruende puerperal sepsis forårsaget af gruppe A-streptokokker.

A case of postpartum streptococcal toxic shock syndrome due to group A streptococci is described. The patient suffered multiorgan failure, was critically ill and stayed in the intensive care unit for 18 days before recovering. The patient received massive antibiotic treatment as well as intravenous immunoglobulin therapy. The case is described to draw attention to the reoccurrence of serious group A streptococcal infections.

Chorioamniotic membranes constitute a competent barrier to group b streptococcus in vitro.

OBJECTIVE: To study the penetration of group B streptococcus (GBS) through human chorioamniotic membranes in vitro. STUDY DESIGN: Chorioamniotic membranes from seventeen healthy women were mounted onto glass cylinders and placed in tissue culture trays constituting a two-compartment system with a maternal compartment internally and a fetal compartment externally. GBS from healthy pregnant women and from newborn babies with sepsis were added to the maternal compartment at densities from 10(7) to 10(9) colony forming units (cfu) per ml. RESULTS: Irrespective of inoculum density, GBS was not recovered from the fetal compartment within a 20 h incubation period. By histology, micro-colonies of GBS were found on the maternal surface after 8 h, but invasion of the morphologically intact membranes was not observed. A five log reduction in cfu occurred in the maternal compartment with amnion when GBS were suspended in saline. CONCLUSION: In this in vitro model the membranes appear to constitute an effective barrier against ascending infection.