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Objectives: Women with chronic rheumatic disease (CRD) are at greater risk of foetal growth restriction than their healthy peers. T2*-weighted magnetic resonance imaging of placenta (T2*P-MRI) is superior to conventional ultrasonography in predicting birth weight and works as a proxy metabolic mirror of the placental function. We aimed to compare T2*P-MRI in pregnant women with CRD and healthy controls. In addition, we aimed to investigate the correlation between T2*P-MRI and birth weight., Methods: Using a General Electric (GE) 1.5 Tesla, we consecutively performed T2*-weighted placental MRI in 10 women with CRD and 18 healthy controls at gestational week (GW)24 and GW32. We prospectively collected clinical parameters during pregnancy including birth outcome and placental weight., Results: Women with CRD had significantly lower T2*P-MRI values at GW24 than healthy controls (median T2*(IQR) 92.1 ms (81.6; 122.4) versus 118.6 ms (105.1; 129.1), p = 0.03). T2*P-MRI values at GW24 showed a significant correlation with birth weight, as the T2*P-MRI value was reduced in all four pregnancies complicated by SGA at birth. Three out of four pregnancies complicated by SGA at birth remained undetected by routine antenatal ultrasound., Conclusion: This study demonstrates reduced T2*P-MRI values and a high proportion of SGA at birth in CRD pregnancies compared to controls, suggesting an increased risk of placental dysfunction in CRD pregnancies. T2*P-MRI may have the potential to focus clinical vigilance by identifying pregnancies at risk of SGA as early as GW24. Key Points • Placenta-related causes of foetal growth restriction in women with rheumatic disease remain to be investigated. • T2*P-MRI values at gestational week 24 predicted foetuses small for gestational age at birth. • T2*P-MRI may indicate pregnant women with chronic rheumatic disease (CRD) in need of treatment optimization., (© 2024. The Author(s).)

Objective: Timing of administration of antibiotics and concentrations in maternal blood and the umbilical cord blood are important prerequisites for optimal intrapartum antibiotic prophylaxis (IAP) of neonatal early-onset group B streptococcus (GBS) disease. This cohort study aimed to explore penicillin concentrations in mothers and infants at birth in relation to time elapsed from administration to delivery and to the minimal inhibitory concentration (MIC) for GBS., Main Outcome Measures: Penicillin G concentrations in maternal and umbilical cord blood in relation to time and dose from administration to time of delivery., Results: In 44 mother-infant dyads, median maternal penicillin G concentration was 0.2 mg/L (IQR 0-0.8 mg/L; range 0-1.6 mg/L). Median infant penicillin G concentration was 1.2 mg/L (IQR 0.5-5.0 mg/L; range 0-12.7 mg/L). In all infants (N=38) born less than 4 hours after the latest IAP administration, penicillin G concentrations far exceeded MIC (0.125 mg/L), even after short time intervals between IAP administration and birth. The highest plasma concentrations were reached in umbilical cord blood within 1 hour from IAP administration to birth.For 44 mother-infant dyads, maternal concentrations were very low compared with their infants'; particularly, very high concentrations were seen in the 20 infants with only one dose of IAP., Conclusion: High concentrations of penicillin G were found in umbilical cord blood of infants born less than 4 hours after IAP administration, well above the MIC for GBS., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: In a country with a high-test frequency, societal lockdown, and pregnancy leave granted from 28 gestational weeks, we investigated SARS-CoV-2 infection in women admitted in labor and their newborn in the pre-vaccine period. Material and methods: A total of 1042 women admitted for delivery in two Danish hospitals agreed to a plasma sample and nasopharyngeal, vaginal, and rectal swabs and to sampling of umbilical cord blood and a nasopharyngeal swab from their newborn at delivery. Plasma samples from women were examined for SARS-CoV-2 antibodies. If antibodies were detected, or the woman had a positive nasopharyngeal swab upon admission or had a household contact with symptoms consistent with COVID-19, SARS-CoV-2 PCR was performed on plasma and swab samples from mother and child. Results: Seventeen women (1.6%) were seropositive. Half the newborn ( n = 9 (53%)) of seropositive mothers were also seropositive. None of the seropositive women or newborns had clinical signs of COVID-19 and all had SARS-CoV-2 PCR negative plasma and swab samples. Conclusion: Adherence to specific national guidelines pertaining to testing, self-imposed isolation, and cautious behaviors among pregnant women likely contributed to the exceptionally low prevalence of both prior and current COVID-19 infections detected at the time of childbirth preceding the routine vaccination of pregnant women in Denmark.

The purpose of this study was to examine the transfer rate of SARS-CoV-2 IgG antibodies in pregnancy and newborns. Two Danish labor wards screened all women for SARS-CoV-2 by PCR upon arrival. Women (n = 99) with a SARS-CoV-2 PCR-positive nasopharyngeal (NP) swab or with a household member with a positive swab at labor or any time during pregnancy, or COVID-19 symptoms upon admission (November 2020 through August 2021), were included. Mother and infant were tested by NP swabs at delivery, and maternal and infant (umbilical cord) venous blood samples were collected. We obtained clinical information including previous PCR test results from the medical records. SARS-Cov-2 IgM and quantified IgG antibodies were measured by enzyme-linked immunosorbent assay and transfer ratios of IgG. We detected IgG antibodies in 73 women and 65 cord blood sera and found a strong correlation between SARS-CoV-2 IgG concentrations in maternal and umbilical cord sera (r = 0.9; p < 0.05). Transfer ratio was > 1.0 in 51 out of 73 (69%) infants and > 1.5 in 26 (35%). We found that transfer was proportional to time from a positive SARS-CoV-2 PCR NP swab to delivery (r = 0.5; p < 0.05). Transfer ratios of SARS-CoV-2 antibodies were associated with time from infection to delivery with transfer ratios of more than 1.0 in the majority of seropositive mother-infant dyads., (© 2023. The Author(s).)

Background and Aims: Inflammatory bowel disease (IBD) activity during pregnancy is associated with adverse pregnancy outcomes. We aimed to identify key clinical characteristics that predict disease activity during pregnancy., Methods: Between January 2008 through 2021, we identified all singleton pregnancies among women with IBD recorded in patient and birth registries at a tertiary IBD centre in Denmark. Maternal and infant data were retrieved from medical records. Demographics, Physicians Global Assessment (PGA) of disease activity 6 months prior to pregnancy and in all three trimesters of pregnancy and pregnancy outcomes were recorded., Results: In 609 pregnancies, we observed 603 (99.0%) live births. Disease activity in one or more trimesters was seen in 283 women (46.5%). UC phenotype was associated with an increase in risk of disease activity (adjusted OR = 2.6 [1.8-3.9]; p < 0.001). Disease activity within 6 months prior to conceiving (169 women [27.7%]) was associated with an increased risk of continuous disease activity during pregnancy (adjusted OR of 5.3 [3.5-8.2]; p < 0.001). Disease activity during a previous pregnancy was associated with an increased risk of flares in subsequent pregnancies (adjusted OR of 3.2 [1.5-6.6]; p = 0.002). Sustained clinical remission throughout pregnancy was associated with an increased probability of normal birth term, birthweight and low risk of fetal growth restriction (FGR) and stillbirth., Conclusion: Predictors for disease activity include disease activity in a previous pregnancy and/or prior to conception, as well as UC phenotype. Reassuringly, women with IBD in remission are not at increased risk of adverse pregnancy outcomes., (© 2022 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)

Primary endothelial cells (ECs), especially human umbilical vein endothelial cells (HUVECs), are broadly used in vascular biology. Gene editing of primary endothelial cells is known to be challenging, due to the low DNA transfection efficiency and the limited proliferation capacity of ECs. We report the establishment of a highly efficient and selection-free CRISPR gene editing approach for primary endothelial cells (HUVECs) with ribonucleoprotein (RNP) complex. We first optimized an efficient and cost-effective protocol for messenger RNA (mRNA) delivery into primary HUVECs by nucleofection. Nearly 100% transfection efficiency of HUVECs was achieved with EGFP mRNA. Using this optimized DNA-free approach, we tested RNP-mediated CRISPR gene editing of primary HUVECs with three different gRNAs targeting the HIF1A gene. We achieved highly efficient (98%) and biallelic HIF1A knockout in HUVECs without selection. The effects of HIF1A knockout on ECs' angiogenic characteristics and response to hypoxia were validated by functional assays. Our work provides a simple method for highly efficient gene editing of primary endothelial cells (HUVECs) in studies and manipulations of ECs functions.

Necrotizing soft tissue infections (NSTI) is a serious infection with a mortality of up to 25% at three months. This review gives an overview of the diagnosis and treatment of NSTI. The prognosis is dependent on rapid surgical treatment, aggressive, prompt removal of infected tissue, broad spectrum antibiotic treatment and supportive care. In cases with suspected or verified infection with Streptococcus pyogenes, adjuvant therapy with immunoglobulins can be considered.

Objectives: Over the past decades new international guidelines recommend that pregnant Systemic lupus erythematosus (SLE) patients are monitored closely in a multi-professional team throughout pregnancy. The importance of low disease activity before pregnancy and continued treatment during pregnancy has been established. However, there is still a high risk of adverse pregnancy outcome (APO).The APO in a Danish SLE cohort was evaluated and compared with the results in a previous study cohort from the same centre and referral area., Methods: This retrospective cohort study used the local patient registry to identify pregnancies in SLE patients followed at the Department of Rheumatology, Aarhus University Hospital, Denmark, from January 2010 to October 2020. In total, 66 pregnancies were registered in 41 women. Data were compared with a previous retrospective study (1990-2010) from the same hospital., Results: Adverse pregnancy outcome occurred in 65% of pregnancies. Forty-seven pregnancies resulted in a live birth, while 15 ended in miscarriages. Compared to the 1990-2010 cohort, a numerical reduction in preterm deliveries (7.58% vs. 17.9%) and emergent caesarean (6.1% vs. 15.5%) was observed, although not reaching statistical significance ( p = .07 in both cases). Further, a higher average birth weight (3045 g vs. 2870 g) as well as a higher number of pregnancies and live births per year were observed. Gestational hypertension was significantly reduced from 23.8% to 13.6% ( p = .05). Significantly more patients were treated with prednisolone (66.7% vs 35.7%, p = .0002), hydroxychloroquine (6% vs. 73.4%, p < .0001) and acetylsalicylic acid (39.3% vs. 73.1%, p = .0001) in 2010-2020 compared to the 1990-2010., Conclusion: We observed significant improvements in the frequency of some APOs in the recent 2010-2020 cohort compared with the previous cohort followed from 1990 to 2010. However, even though a specialized multi-professional team closely follows SLE patients through their pregnancies, pregnancy in SLE still carries a high risk of APO.

Competing Interests: I declare no competing interests.

Pigs are valuable large animal models for biomedical and genetic research, but insights into the tissue- and cell-type-specific transcriptome and heterogeneity remain limited. By leveraging single-cell RNA sequencing, we generate a multiple-organ single-cell transcriptomic map containing over 200,000 pig cells from 20 tissues/organs. We comprehensively characterize the heterogeneity of cells in tissues and identify 234 cell clusters, representing 58 major cell types. In-depth integrative analysis of endothelial cells reveals a high degree of heterogeneity. We identify several functionally distinct endothelial cell phenotypes, including an endothelial to mesenchymal transition subtype in adipose tissues. Intercellular communication analysis predicts tissue- and cell type-specific crosstalk between endothelial cells and other cell types through the VEGF, PDGF, TGF-β, and BMP pathways. Regulon analysis of single-cell transcriptome of microglia in pig and 12 other species further identifies MEF2C as an evolutionally conserved regulon in the microglia. Our work describes the landscape of single-cell transcriptomes within diverse pig organs and identifies the heterogeneity of endothelial cells and evolutionally conserved regulon in microglia., (© 2022. The Author(s).)

Introduction: Induction of labor (IOL) is used to improve the outcome of pregnancy for mother and child. Since 2013, oral misoprostol has been used for IOL at Aarhus University Hospital, Denmark. The purpose of the present paper is to describe our experience of the use of a new, 25-µg misoprostol tablet commercially manufactured for the purpose of IOL regarding efficacy and outcome for mother and neonate in both an inpatient and an outpatient regimen., Material and Methods: We performed an audit from 1 April 2016, including data on all IOL in women with singleton pregnancies until 1000 consecutive women were registered. Data from 976 consecutive women with gestational age ≥37 +0  weeks induced in accordance with the "Aarhus protocol" were included in the present analyses. All inductions were by oral misoprostol. Outpatient induction is standard procedure in low-risk pregnancies, that is, pregnancies with a healthy mother and no signs of placental insufficiency. In the outpatient IOL, the first dose of misoprostol is administered after a normal cardiotocography registration at the hospital. Subsequent doses are taken at home according to a predefined regimen. Following delivery, data on baseline variables and outcome variables for the mother and neonate were retrieved from the medical records., Results: In 71.9% of cases, the women were induced in an outpatient regimen. Delivery within 24 hours was achieved in 38.8% of women (nulliparous 32.3%, multiparous 50.9%) and within 48 hours in 70.1% (nulliparous 66.2%, multiparous 77.2%). Hyperstimulation during induction occurred in 0.6%. The mode of delivery was spontaneous vaginal in 75.5% of cases. The cesarean section rate was 14.9% (nulliparous 20.7%, multiparous 4.1%). Apgar <7 at 5 minutes and pH <7.0 in the umbilical artery was seen in 0.9% and 0.7%, respectively., Conclusions: Induction of labor by a commercially produced low-dose (25 µg) misoprostol tablet for oral induction according to the "Aarhus protocol" is feasible in an outpatient as well as an inpatient regimen. Delivery was achieved within 48 hours for 70.1% of women. Few adverse events were seen; however, the audit was underpowered for safety., (© 2020 Nordic Federation of Societies of Obstetrics and Gynecology.)

Introduction: The purpose of this study is to describe bacteriuria with regard to the uropathogens found in relation to the frequency of urine culture tests in a contemporary cohort of pregnant Danish women., Methods: A historical cohort study of 24,817 pregnant women registered in the Danish Fetal Medicine Database at Aarhus University Hospital, from 2010 to 2014. Social security numbers were linked to the microbiological database with the registration of 17,233 urine cultures in 8,807 women. Bacteriuria was defined as 1 × 10 5  CFU/ml, with a maximum of two urinary pathogens. Streptococcus agalactiae (GBS) was included with 1 × 10 4  CFU/ml. Data are presented as numbers and proportions in percent. Logistic regression on predictors are presented as crude and adjusted odds ratios (OR c /OR a ) with 95% confidence intervals (CIs)., Results: 42% had a urine sample culture test at the hospital-the majority only once during pregnancy. 96% of all urine culture tests were negative. The bacteriuria incidence was 5.6%. The most frequent uropathogenic bacteria isolated were Escherichia coli (49%), GBS (29%), and Enterococci (10%). We identified subgroups of women with increased likelihood of bacteriuria during pregnancy: age < 25 years, OR a 1.60 (CI 1.26 to 2.02, p < 0.001); age > 34 years, OR a 1.28 (CI 1.01 to 1.61, p = 0.040); Afro-Caribbean origin, OR a 1.872 (CI 1.13 to 3.07, p = 0.014); Asian origin, OR a 2.07 (CI 1.29 to 3.32, p = 0.002); and mixed ethnicity OR a 2.34 (CI 1.23 to 4.46, p = 0.010). Women delivering preterm were more likely to have an episode of bacteriuria during pregnancy OR 2.05 (CI 1.36 to 3.09, p = 0.001)., Conclusions: 96% of urine culture tests in pregnant women are negative. Optimized urine sampling may change this . Escherichia coli and GBS are predominant uropathogens. Younger and elder women, certain ethnical groups, and women delivering preterm seem more likely to have bacteriuria during pregnancy., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 Vinnie H. Greve et al.)

Objective: We have recently introduced intrapartum PCR-testing for group B streptococcus (GBS) in women in labor with prolonged rupture of membranes or preterm delivery to offer intrapartum antibiotic prophylaxis only for GBS positive women.The goal of the present study is to report our experience and results from the first half year of GBS testing., Study Design: This is a retrospective study. Rectovaginal swabs from 321 women presenting in the labor ward with pre-labor rupture of membranes for >14 h/rupture of membranes during delivery for >14 h, or labor between gestational weeks 35 0/7 and 36 6/7 from February 7, 2017 to August 6, 2017, were tested.We performed a molecular GBS test (Xpert GBS®, Cepheid Ltd., Sunnyvale, USA).Data from patient files including mode of delivery, use of antibiotics, infection of mother and child are presented in more detail.Data on the PCR results from the first year of testing were also collected., Results: In the first half-year of testing a positive GBS test result was found in 58 (18.1%) and a negative test result in 263 women (81.9%). No invalid test result was achieved.The indication for performing PCR testing was PROM > 14 h or rupture of membranes during labor for >14 h in 266 women (82.9%) and labor in gestational weeks 35 0/7-36 6/7 in 44 women (13.7%). In the remaining 11 women, the PCR test was performed for other reasons.Of the 321 women tested 126 (39%) received antibiotics during labor.Ten women (3.4%) were treated after delivery on suspicion of infection. 25 newborns (7.8%) were treated with antibiotics. In 11 cases, the treatment was stopped after 2-4 days as there were no signs of infection., Conclusions: The introduction of the intrapartum GBS test in selected groups of women who gave birth in our department has been well accepted by the women, the midwifes and doctors. The result of the test is available within two hours, and as we only offer intrapartum antibiotic prophylaxis to GBS-positive women, we have reduced the use of antibiotics to approximately 40% in the groups tested, without an increase of infection in mother or child., (© 2019 The Authors.)

Changes in vaginal discharge are often caused by imbalance in the vaginal microflora, and laboratory testing is usually of little use, as most microbes detected are commensals. In-office diagnosis in general practice using wet mount microscopy and Amsel criteria is helpful and often sufficient to ensure correct diagnosis and treatment. Laboratory testing of vaginal discharge should only be performed, if sexually transmitted disease is suspected, if there is treatment failure or inconclusive wet mount prior to gynaecological surgery, and in pregnant women with recurrent miscarriage or preterm birth.

Introduction: Many pregnant women are treated with antibiotics during labor to prevent transmission of group B streptococcus (GBS, Streptococcus agalactiae) to their baby during passage of the birth canal, and so reduce the risk of serious infection of the newborn. Methods for intrapartum testing for GBS have been introduced to select women to whom intrapartum antibiotic prophylaxis should be offered. For such an intrapartum test to be useful in clinical practice, it has to be specific as well as sensitive. The aim of the present study is to evaluate the accuracy of the polymerase chain reaction (PCR) assay compared with an optimized culture method for GBS., Material and Methods: In the period from 12 May 2015 to 18 December 2015 we collected rectovaginal swabs from 106 women in the labor ward presenting in labor between gestational week 35 +0 and 36 +6 or presenting with prelabor/preterm prelabor rupture of membranes (PROM/PPROM) for > 14 h after gestational week 34 +0 . We performed GBS culture (reference standard) and a molecular GBS test (Xpert GBS, Cepheid Ltd., Sunnyvale, CA, USA)., Results: Based on intrapartum culture, 23.6% (25/106) were colonized with GBS. Intrapartum PCR showed a colonization rate of 25.7% (27/105). The sensitivity of the test was 100% (86.28-100%). The specificity of the test was 97.5% (91.26-99.70%). The positive predictive value was 92.6%. In one case, we had no result with PCR testing, giving an invalid test rate of < 1%., Conclusion: The PCR test has sufficient accuracy to direct intrapartum antibiotic prophylaxis for GBS transmission during delivery., (© 2017 Nordic Federation of Societies of Obstetrics and Gynecology.)

Group A streptococci infection has re-emerged since the 1980s and onward, despite the awareness of the etiology and the use of penicillin. It now accounts for more than 75,000 deaths worldwide every year. Postpartum women have a 20-fold increased incidence of group A streptococci disease compared to non-pregnant women. This review focuses on the epidemiology, pathophysiology, clinical presentation, prevention and treatment of group A streptococcal infection in pregnancy., Search Strategy: We searched the following electronic databases from 1980-March 2016: PubMed-Medline, Embase, SveMed+, Bibliotek.dk, Cinahl and Cochrane database using following MESH terms or Emtree terms; (Fasciitis, Necrotizing), Soft Tissue Infection, Streptococcus Pyogenes, Postpartum Period, Pregnancy, (Shock, Septic), Microbiology, Epidemiology, Disease Management. We identified 439 records. After literature screening we ended up with 66 records. Group A streptococci infection, and in particular streptococcal toxic shock syndrome and necrotizing fasciitis, can be life threatening. Despite advanced surgery, antibiotics and supportive therapy, there is still a high mortality associated with these infections. The clinical picture can vary greatly and awareness of the condition and its ability to progress rapidly is crucial for prompt treatment. A profound review on the subject is presented in the paper., (Copyright © 2017 Elsevier B.V. All rights reserved.)

We report 2 cases of true uterine artery aneurysms diagnosed during pregnancy. Both cases presented with nonspecific symptoms such as urethral obstruction, minimal vaginal bleeding and lower abdominal pain in the 2nd trimester. Both aneurysms were diagnosed by color Doppler ultrasound. In the first case labor was induced at 37 + 4 weeks of gestation. However, due to sudden fetal distress and maternal abdominal pain, an emergency Caesarean section was performed during labor, and 3 liters of intra-peritoneal blood were encountered upon laparotomy, secondary to a ruptured uterine artery aneurysm. In the second case, an elective Caesarean section was scheduled at 38 + 3 weeks of gestation, and the delivery and postpartum period were uncomplicated. Albeit a rare condition, a uterine artery aneurysm should be among the differential diagnosis considered in pregnant women who present with pelvic and vaginal masses, vague bladder symptoms or radiating pelvic pain. The diagnosis is readily made by color Doppler imaging. Elective Caesarean section should be the preferred mode of delivery to avoid rupture of the aneurysm during labor., (© 2016 S. Karger AG, Basel.)

Introduction: Bacterial vaginosis (BV) is characterized by a dysbiosis of the vaginal microbiota with a depletion of Lactobacillus spp. In pregnancy, prevalence's between 7 and 30% have been reported depending on the study population and the definition. BV may be associated with an increased risk of spontaneous preterm delivery (sPTD). However, it is controversial whether or not BV-positive pregnant women will benefit from treatment to reduce the risk of sPTD. We could not identify any good-quality guideline addressing this issue. Consequently we aimed to produce this clinical recommendation based on GRADE., Material and Methods: Systematic literature searches were conducted in the following databases: Guidelines International Network: G-I-N, Medline, Embase, The Cochrane Database of Systematic Reviews, Web of Science and http://www.clinicaltrials.gov from 1999 to 3 October 2014. Hence, nine guidelines, 34 reviews, 18 randomized controlled trials and 12 observational studies were included., Results: The GRADE quality of evidence was consistently low or very low, primarily because none of the risk ratios (RR) for the risk of sPTD at <37 weeks were statistically significant. Concerning treatment with metronidazole, RR was 1.11 (95% CI 0.93-1.34) in low-risk pregnancies and 0.96 (95% CI 0.78-1.18) in high risk pregnancies. Concerning treatment with clindamycin at any gestational age, the RR was 0.87 (95% CI 0.73-1.05)., Conclusion: This systematic review gives a strong recommendation against treatment with metronidazole and a weak recommendation against treatment with clindamycin to reduce the sPTD rate in both high-risk and low-risk pregnancies with BV., (© 2016 Nordic Federation of Societies of Obstetrics and Gynecology.)

Objective: To evaluate the serological response in pregnant Danish women immunized during the 2009 pandemic by serologic infection or by vaccination with influenza A(H1N1) Pandemrix(®) and describe levels of passively acquired maternal antibody in their offspring., Design: Observational cohort study., Setting: Department of Obstetrics, Aarhus University Hospital, Skejby, Denmark, October to December 2009., Population: Pregnant women and their offspring, Methods: Serological analysis of antibodies to influenza A(H1N1)pdm09 by hemagglutination inhibition assay in 197 women and their offspring. Blood samples were collected consecutively at delivery from the mother and the umbilical cord. In a subgroup of 124 of the 197 women, an additional blood sample from gestational weeks 9-12 was available for analysis., Main Outcome Measures: Seroconversion, geometric mean titer, geometric mean-fold rise and protective antibodies., Results: 33 of the 124 subgroup women (27%) seroconverted during pregnancy, 79% after vaccination and 17% after serologic infection (p < 0.001). The geometric mean titer after delivery in non-vaccinated, non-serologically infected women was 17.1 (95%CI 15.7-18.6). The geometric mean titer increased significantly after serologic infection with H1N1 [76.5 (95%CI 51.3-113.9), p < 0.001] and after vaccination [589.6 (95%CI 339.3-1024.7), p < 0.001]. The geometric mean-fold rise (mother at delivery/mother early pregnancy) was significantly higher after vaccination [2.23 (1.93-2.54)] than after serologic infection [1.73 (1.59-1.87), p = 0.013]. In newborns of vaccinated mothers, 89.5% had protective antibody levels compared with 15.8% in newborns of serologically infected mothers (p < 0.001)., Conclusions: Influenza vaccination during pregnancy confers passive immunity to the newborn., (© 2015 Nordic Federation of Societies of Obstetrics and Gynecology.)

Many resources are used in developing guidelines for the treatment and handling of different diseases and clinical situations. It is important to evaluate the effect of these guidelines; are they being followed and do they have the desired impact on patient care? This report describes a quality control evaluation of whether the implementation of a new PROM (prelabour rupture of membranes) management guideline at Department Y at the Aarhus University Hospital had the wanted effect on the length of labour, use of prophylactic antibiotics, frequency of neonatal admission and neonatal infection.

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., (© 2013 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2013 RCOG.)

Objective: To evaluate the effect of laparoscopic abdominal cerclage performed as an interval procedure in non-pregnant women at high risk of second trimester spontaneous abortion and early preterm birth., Design: Observational study., Sample: Fifty-two consecutive patients at high risk of preterm birth., Setting: Department of Obstetrics and Gynecology, Aarhus University Hospital., Methods: Patients were registered prospectively. Indications for surgery included classical cervical insufficiency, preterm premature rupture of membranes (PPROM) or two conizations/cervical amputation. Outcome of subsequent pregnancies was registered., Main Outcome Measures: Gestational age in subsequent pregnancies., Results: No operative or postoperative complications were observed. A total of 45 pregnancies were registered during the observation period. Among 36 pregnancies lasting beyond the 16th week of gestation, 30 women (83.3%) gave birth by cesarean section after 36 weeks of gestation and the overall mean gestational age was 37.4 weeks compared with a mean gestational age of 25.2 weeks of the pregnancies prior to the cerclage. The cesarean sections were uncomplicated in all but one patient, where a re-laparotomy was needed six hours later due to atonic postpartum hemorrhage without evident bleeding through the cervix., Conclusion: Laparoscopic abdominal cerclage is a feasible and safe procedure. Obstetrical outcomes are encouraging but prospective studies are needed to define the effectiveness of the laparoscopic cerclage compared with the traditional transvaginal approach., (© 2012 The Authors Acta Obstetricia et Gynecologica Scandinavica© 2012 Nordic Federation of Societies of Obstetrics and Gynecology.)

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.

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.

Background: To characterize the potential for adaptive immune protection in cervical mucus plugs with respect to immunoglobulin isotypes and effector cells (phagocytes)., Methods: Thirty-one cervical mucus plugs were collected from healthy women in labor at term. The cervical mucus plugs were allocated either to analysis of immunoglobulins by enzyme-linked immunosorbent assay (ELISA), gel chromatography and Western blotting (n = 20) or to microscopical, including immunocytochemical, analyses. The levels of immunoglobulin in the plugs were compared to the levels in 10 samples of ovulatory cervical mucus from nonpregnant women., Results: In the cervical mucus plugs, levels of immunoglobulin G (IgG) [median 3270 microg/mL (100-14 500)] and IgA [540 (22-2820)], but not IgM [30.5 (1.0-160)], were significantly elevated compared to cervical mucus from nonpregnant women (p < 0.02 for IgG and IgA). The IgG : IgA ratio in the plugs was also elevated (p < 0.02). The proportion of secretory immunoglobulin A (SIgA) relative to total IgA in the plugs ranged from 16 to 65% (n = 5). IgA and IgG were largely intact. Microscopically, the vagina-proximal part of the cervical mucus plugs contained bacteria and was rich in cells, mainly phagocytes. Conversely, the uterine part contained few cells., Conclusion: The high immunoglobulin levels in combination with the presence of phagocytes suggest a potential for adaptive immune defense in the cervical mucus plug, which, together with innate immune factors, may act as an immunological gatekeeper protecting the fetomaternal unit against infection from the vagina.

Background: Relaxin has been proposed as a hormone involved in the collagen remodeling of the utero-placental unit., Materials and Methods: Human fetal membrane explants were incubated with H1 or H2 relaxin for 48 hours and stretched until rupture in a materials testing machine. Co-incubation with a synthetic collagenase inhibitor was performed in order to examine whether the effects of relaxin could be inhibited. The effects on hydroxyproline and histology were evaluated., Results: Biomechanical testing showed that H2 relaxin induced a biphasic weakening of human fetal membranes, an effect that was abolished after co-incubation with a collagenase inhibitor. H1 relaxin produced no significant effects on the biomechanical properties. The effects of H2 relaxin on the biomechanical properties were, however, not followed by changes in the hydroxyproline concentration or the histology., Conclusion: H2 relaxin had an effect on human fetal membranes and this effect may be mediated through collagenases.

Objective: The cervical mucus plug is positioned between the microbe-rich vagina and the normally sterile uterine cavity, which suggests a host defense function, but few relevant data are available. We analyzed the composition and antimicrobial activity of cervical mucus plugs., Study Design: Cervical mucus plugs were collected from healthy women at delivery. Groups of plugs were randomly selected for electrolyte analysis, antimicrobial activity assays against group B Streptococcus, Escherichia coli, Candida albicans, and assays of known antimicrobial polypeptides., Results: Both intact cervical mucus plugs and their aqueous extracts exhibited antimicrobial activity against aerobic microbes, in the order of potency: group B Streptococcus > E coli > C albicans. Semiquantitative Western blotting of extracts showed that secretory leukoprotease inhibitor, lysozyme, lactoferrin, and neutrophil defensins were present at concentrations that were sufficient for antimicrobial activity., Conclusion: The cervical mucus plug is not only a mechanical but also a chemical barrier to infection that ascends from the vagina.

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.

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.

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.

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

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.

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.