Timing and dosage of intrapartum prophylactic penicillin for preventing early-onset group B streptococcal disease: assessing maternal and umbilical cord blood concentration.

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.

Reduced T2*-weighted placental MRI predicts foetal growth restriction in women with chronic rheumatic disease-a Danish explorative study.

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.

Comparatively low rates of COVID-19 in women admitted in labor and their newborns prior to routine vaccination of pregnant women: insights from Denmark.

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.

Transplacental transfer of SARS-CoV-2 antibodies: a cohort study.

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.

[Necrotizing fasciitis].

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.

Improved pregnancy outcomes in systemic lupus erythematosus: A retrospective study of pregnancies from a single centre in Denmark from 2010-2020 compared with the period 1990-2010.

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.

Endothelial cell heterogeneity and microglia regulons revealed by a pig cell landscape at single-cell level.

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-ß, 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.

HIF1A Knockout by Biallelic and Selection-Free CRISPR Gene Editing in Human Primary Endothelial Cells with Ribonucleoprotein Complexes.

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.

Women's body mass index and oral administration of Misoprostol for induction of labor - A retrospective cohort study.

Pregnant women who are obese are at greater risk of pregnancy complications, including preeclampsia, gestational diabetes, and macrosomia, leading to an increased likelihood of induced labor. Little is known about pregnant women with obesity and the dose of Misoprostol needed for induction of labor (IOL). To investigate whether the cumulative dose of Misoprostol needed for induction of labor (IOL) is associated with women's body mass index (BMI), we conducted a retrospective study of the use of oral Misoprostol for IOL at the Department of Obstetrics and Gynecology, Aarhus University Hospital - a tertiary referral delivery unit with 4800 deliveries a year. Data on IOL among 1637 women with singleton pregnancies was collected in the period January 1st, 2014, to October 4th, 2017. Low-risk women were induced in an outpatient setting. Primary outcomes were Misoprostol dose, time between start of induction (first dose of Angusta®) and completed delivery, and mode of delivery. Secondary outcomes were neonatal data as Apgar score and pH of the umbilical artery. In this study, we found the total dose of Misoprostol needed for induction increased significantly with increasing BMI (p < 0.005). The time to delivery and the risk of Cesarean section increased with rising BMI class. However, 76% of inductions among the women with obesity ended in a vaginal delivery. For the neonatal outcomes, a total of 16 children had an Apgar score below 7 at five minutes and 14 had a pH less than 7.0; none of these results differed significantly between BMI classes. The perinatal and maternal mortality rate was 0%.

[Diagnosis of vaginal discharge].

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.

Group A streptococci infection. A systematic clinical review exemplified by cases from an obstetric department.

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.

Two Cases of True Uterine Artery Aneurysms Diagnosed during Pregnancy.

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.

[Implementation of new guidelines for management of prelabour rupture of membranes did not have the desired effect]. / Indførelse af ny instruks for primær vandafgang til termin gav ikke den ønskede effect.

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.

Immunoglobulin levels and phagocytes in the cervical mucus plug at term of pregnancy.

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.

Biphasic effect of relaxin, inhibitable by a collagenase inhibitor, on the strength of human fetal membranes.

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.

Antimicrobial factors in the cervical mucus plug.

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.