Variability in COVID-19 Symptom Presentation During Pregnancy and its Impact on Maternal and Infant Outcomes Across the Pandemic.

BACKGROUND: With the dominance of different SARS-CoV-2 variants, the severity of COVID-19 has evolved. We aimed to investigate the difference in symptom prevalence and the association between symptoms and adverse pregnancy outcomes during the dominance of Wild-type/Alpha, Delta, and Omicron. METHODS: COVID-19 related symptom prevalence, maternal and specific neonatal outcomes of 5431 pregnant women registered in this prospective study were compared considering the dominant virus variant. Logistic regression models analyzed the association between specific symptoms and intensive care unit (ICU) admission or preterm birth. RESULTS: Infection with the Delta variant led to an increase in the symptom burden compared to the Wild-type/Alpha variant and the highest risk for respiratory tract symptoms, feeling of sickness, headache, and dizziness/drowsiness. An infection with the Omicron variant was associated with the lowest risk of dyspnea and changes in smell/taste but the highest risk for nasal obstruction, expectoration, headaches, myalgia, and fatigue compared to the Wild-type/Alpha and Delta variant dominant periods. With the progression of the Wild-type/Alpha to the Delta variant neonatal outcomes worsened. Dyspnea and fever were strong predictors for maternal ICU admission and preterm birth independent of vaccination status or trimester of infection onset. CONCLUSION: The symptom burden increased during the Delta period and was associated with worse pregnancy outcomes than in the Wild-type/Alpha area. During the Omicron dominance there still was a high prevalence of less severe symptoms. Dyspnea and fever can predict a severe maternal illness.

Off-Label Use of an External Hand Fixator for Craniomaxillofacial Fractures-An Anatomical Feasibility Study.

BACKGROUND: The lack of resources limits the treatment of craniomaxillofacial fractures (CMF) in low-income countries (LIC). Therefore, Barton bandages and/or interdental wiring are considered in these regions. Fracture reduction is maintained by permanent occlusion for 6 weeks, which often leads to limited compliance and dissatisfying results. The aim of this cadaver-based study is to evaluate the feasibility of the use of an external face fixator (EFF) for the treatment of CMF, its biomechanical values and to define the optimal pin insertion points and angles. MATERIALS AND METHODS: An AO hand fixator was used. CMF of types Le Fort 1-3 with split fractures of the hard palate were treated with EFF on 13 anatomical specimens. Fractures were created using a chisel, and pins were placed in specific anatomical regions. The maximal pull-out force [N] of pins was analysed by a tensile force gauge, and Fmax of the mandibular pins was evaluated. Computer tomography scans were performed on the healthy, fractured and EFF-treated skulls. RESULTS: The pull-out forces for the single pins were mandibular pins (n = 15, median 488.0 N), supraorbital pins (n = 15, median 455.0 N), zygomatic pins (n = 14, median 269.1 N), medial hard palate pins (n = 12, median 208.4 N) and lateral hard palate pins (n = 8, median 49.6 N). CONCLUSIONS: The results indicate that the operation technique is feasible, and the stability of the EFF is sufficient for maintaining the reduction. The required pins can safely be inserted into the described areas with good reduction results. Using EFF offers a feasible alternative to the non-surgical treatment of CMF in LIC.

Women with Endometriosis-Who Is at Risk for Complications Associated with Pregnancy and Childbirth? A Retrospective Case-Control Study.

Women with endometriosis (EM), particularly the manifestations of adenomyosis (AM) and deep infiltrating endometriosis (DIE), suffer from pain and sterility. DIE also appears with several specific obstetric complications. To determine the risk profile, we designed a retrospective case-control study. Primary outcomes were defined as the risk of preterm birth and caesarean delivery (CD). Primiparous singleton pregnancies in women with DIE were compared with controls without EM. We matched for mode of conception and maternal age. A total of 41 women diagnosed with DIE and 164 controls were recruited. A total of 92.7% of the cases were also diagnosed with AM. Preterm birth occurred in 12.2% of cases and in 6.7% of controls. The difference was not statistically significant (OR: 1.932; 95% CI: 0.632-5.907). The rate of CD was similar in both groups. Remarkably, placental implantation disorders in the form of placenta praevia were eight times more frequent in women with DIE (9.8%) than in controls (1.2%, OR: 8.757; 95% CI: 1.545-49.614). Neonatal outcome was similar in both groups. Four out of fourteen cases reported abdominal wall endometriosis after CD. Women with DIE/AM and with placenta praevia are at risk of bleeding complications. After CD, they can develop abdominal wall EM. We therefore suggest evaluating the birth mode in each woman with DIE/AM.

Successful Prenatal Treatment of Cardiac Rhabdomyoma in a Fetus with Tuberous Sclerosis.

Cardiac rhabdomyomas are a possible early manifestation of the Tuberous Sclerosis Complex (TSC). They often regress spontaneously but may grow and cause cardiac dysfunction, threatening the child's life. Treatment with rapalogs can stop the growth of these cardiac tumors and even make them shrink. Here, we present the case of a successful treatment of a cardiac rhabdomyoma in a fetus with TSC by administering sirolimus to the mother. The child's father carries a TSC2 mutation and the family already had a child with TSC. After we confirmed the TSC diagnosis and growth of the tumor with impending heart failure, we started treatment at 27 weeks of gestation. Subsequently, the rhabdomyoma shrank and the ventricular function improved. The mother tolerated the treatment very well. Delivery was induced at 39 weeks and 1 day of gestation and proceeded without complications. The length, weight, and head circumference of the newborn were normal for the gestational age. Rapalog treatment was continued with everolimus. Metoprolol and vigabatrin were added because of ventricular preexcitation and epileptic discharges in the EEG, respectively. We provide the follow-up data on the child's development in her first two years of life and discuss the efficacy and safety of this treatment.

Gestational diabetes mellitus and COVID-19: results from the COVID-19-Related Obstetric and Neonatal Outcome Study (CRONOS).

BACKGROUND: Gestational diabetes mellitus is one of the most frequent pregnancy complications with a global prevalence of 13.4% in 2021. Pregnant women with COVID-19 and gestational diabetes mellitus are 3.3 times more likely to be admitted to an intensive care unit than women without gestational diabetes mellitus. Data on the association of gestational diabetes mellitus with maternal and neonatal pregnancy outcomes in pregnant women with SARS-CoV-2 infection are lacking. OBJECTIVE: This study aimed to investigate whether gestational diabetes mellitus is an independent risk factor for adverse maternal and fetal and neonatal outcomes in pregnant women with COVID-19. STUDY DESIGN: The COVID-19-Related Obstetric and Neonatal Outcome Study is a registry-based multicentric prospective observational study from Germany and Linz, Austria. Pregnant women with clinically confirmed COVID-19 were enrolled between April 3, 2020, and August 24, 2021, at any stage of pregnancy. Obstetricians and neonatologists of 115 hospitals actively provided data to the COVID-19-Related Obstetric and Neonatal Outcome Study. For collecting data, a cloud-based electronic data platform was developed. Women and neonates were observed until hospital discharge. Information on demographic characteristics, comorbidities, medical history, COVID-19-associated symptoms and treatments, pregnancy, and birth outcomes were entered by the local sites. Information on the periconceptional body mass index was collected. A primary combined maternal endpoint was defined as (1) admission to an intensive care unit (including maternal mortality), (2) viral pneumonia, and/or (3) oxygen supplementation. A primary combined fetal and neonatal endpoint was defined as (1) stillbirth at ≥24 0/7 weeks of gestation, (2) neonatal death ≤7 days after delivery, and/or (3) transfer to a neonatal intensive care unit. Multivariable logistic regression analysis was performed to evaluate the modulating effect of gestational diabetes mellitus on the defined endpoints. RESULTS: Of the 1490 women with COVID-19 (mean age, 31.0±5.2 years; 40.7% nulliparous), 140 (9.4%) were diagnosed with gestational diabetes mellitus; of these, 42.9% were treated with insulin. Overall, gestational diabetes mellitus was not associated with an adverse maternal outcome (odds ratio, 1.50; 95% confidence interval, 0.88-2.57). However, in women who were overweight or obese, gestational diabetes mellitus was independently associated with the primary maternal outcome (adjusted odds ratio, 2.69; 95% confidence interval, 1.43-5.07). Women who were overweight or obese with gestational diabetes mellitus requiring insulin treatment were found to have an increased risk of a severe course of COVID-19 (adjusted odds ratio, 3.05; 95% confidence interval, 1.38-6.73). Adverse maternal outcomes were more common when COVID-19 was diagnosed with or shortly after gestational diabetes mellitus diagnosis than COVID-19 diagnosis before gestational diabetes mellitus diagnosis (19.6% vs 5.6%; P<.05). Maternal gestational diabetes mellitus and maternal preconception body mass index of ≥25 kg/m2 increased the risk of adverse fetal and neonatal outcomes (adjusted odds ratio, 1.83; 95% confidence interval, 1.05-3.18). Furthermore, overweight and obesity (irrespective of gestational diabetes mellitus status) were influential factors for the maternal (adjusted odds ratio, 1.87; 95% confidence interval, 1.26-2.75) and neonatal (adjusted odds ratio, 1.81; 95% confidence interval, 1.32-2.48) primary endpoints compared with underweight or normal weight. CONCLUSION: Gestational diabetes mellitus, combined with periconceptional overweight or obesity, was independently associated with a severe maternal course of COVID-19, especially when the mother required insulin and COVID-19 was diagnosed with or after gestational diabetes mellitus diagnosis. These combined factors exhibited a moderate effect on neonatal outcomes. Women with gestational diabetes mellitus and a body mass index of ≥25 kg/m2 were a particularly vulnerable group in the case of COVID-19.

Maternal and neonatal outcomes of pregnancies with COVID-19 after medically assisted reproduction: results from the prospective COVID-19-Related Obstetrical and Neonatal Outcome Study.

BACKGROUND: Severe acute respiratory syndrome coronavirus type 2 infections in pregnancy have been associated with maternal morbidity, admission to intensive care, and adverse perinatal outcomes such as preterm birth, stillbirth, and hypertensive disorders of pregnancy. It is unclear whether medically assisted reproduction additionally affects maternal and neonatal outcomes in women with COVID-19. OBJECTIVE: To evaluate the effect of medically assisted reproduction on maternal and neonatal outcomes in women with COVID-19 in pregnancy. STUDY DESIGN: A total of 1485 women with COVID-19 registered in the COVID-19 Related Obstetric and Neonatal Outcome Study (a multicentric, prospective, observational cohort study) were included. The maternal and neonatal outcomes in 65 pregnancies achieved with medically assisted reproduction and in 1420 spontaneously conceived pregnancies were compared. We used univariate und multivariate (multinomial) logistic regressions to estimate the (un)adjusted odds ratios and 95% confidence intervals for adverse outcomes. RESULTS: The incidence of COVID-19-associated adverse outcomes (eg, pneumonia, admission to intensive care, and death) was not different in women after conceptions with COVID-19 than in women after medically assisted reproduction pregnancies. Yet, the risk of obstetrical and neonatal complications was higher in pregnancies achieved through medically assisted reproduction. However, medically assisted reproduction was not the primary risk factor for adverse maternal and neonatal outcomes including pregnancy-related hypertensive disorders, gestational diabetes mellitus, cervical insufficiency, peripartum hemorrhage, cesarean delivery, preterm birth, or admission to neonatal intensive care. Maternal age, multiple pregnancies, nulliparity, body mass index >30 (before pregnancy) and multiple gestation contributed differently to the increased risks of adverse pregnancy outcomes in women with COVID-19 independent of medically assisted reproduction. CONCLUSION: Although women with COVID-19 who conceived through fertility treatment experienced a higher incidence of adverse obstetrical and neonatal complications than women with spontaneous conceptions, medically assisted reproduction was not the primary risk factor.

Pathogenesis of Endometriosis: The Origin of Pain and Subfertility.

Endometriosis (EM) and adenomyosis (AM) are common conditions with pain and infertility as the principal symptoms. The pathophysiology of pain in EM and AM comprises sensory and somatoform pain mechanisms. Over time, these may aggravate and lead to individual complex disease patterns if not diagnosed and treated. Despite the known facts, several years often pass between the onset of symptoms and diagnosis. Chronic pain disorders with changes on a neuronal level frequently arise and are linked to depressive disorders, with the process becoming a vicious cycle. Additionally, women with EM and AM suffer from sub- and infertility. Low fecundity rates are caused by anatomical changes in combination with behavioral changes in the sexual activity of women with chronic pain as well as local proinflammatory factors that not only decrease implantation rates but also promote early abortions.

Deep Infiltrating Endometriosis and Adenomyosis: Implications on Pregnancy and Outcome.

Endometriosis (EM), especially deep infiltrating endometriosis (DIE) and adenomyosis (AM), are known to cause pain and sterility in young women. More recently, they have also been described as risk factors for obstetric complications. While the pathophysiology is not yet completely understood, they seem to share a common origin: archimetrosis. Methods: A systematic literature review was conducted to summarize the existing evidence on DIE and AM as risk factors for obstetric complications. Results: Preterm birth, caesarean section delivery (CS) and placental abnormalities are associated with the diagnosis of DIE and AM. Women with AM seem to experience more often hypertensive pregnancy disorders, premature rupture of membranes and their children are born with lower birth weights than in the control groups. However, many of the studies tried to evaluate AM, EM and DIE as separate risk factors. Moreover, often they did not adjust for important confounders such as multiple pregnancies, parity, mode of conception and maternal age. Therefore, prospective studies with larger numbers of cases and appropriate adjustment for confounders are needed to explore the pathophysiology and to prove causality.

In vivo horizontal gene transfer of the carbapenemase OXA-48 during a nosocomial outbreak.

BACKGROUND: OXA-48 is a highly prevalent carbapenemase and has been isolated worldwide. Here, we investigate the in vivo horizontal gene transfer (HGT) of blaOXA-48 from Klebsiella pneumoniae to Escherichia coli in an infected patient. METHODS: Bacterial isolates were characterized by susceptibility testing, multilocus sequence typing, DiversiLab, and plasmid analyses. Transferability of blaOXA-48 was evaluated by in vitro transconjugation using the outbreak strain and E. coli J53. In vivo transconjugation was investigated using the larvae of the greater wax moth (Galleria mellonella) and low-complexity-microbiota mice. RESULTS: OXA-48-harboring K. pneumoniae isolates belonging to ST14 were isolated during a nosocomial outbreak from 6 patients. Molecular and epidemiological analyses revealed the HGT of an approximately 60-kb OXA-48-containing IncL/M-type plasmid from K. pneumoniae to E. coli belonging to the novel ST666 in a patient. In vitro conjugation experiments revealed a transconjugation frequency of 8.7 × 10(-7). HGT of OXA-48 in a newly developed in vivo model using G. mellonella larvae revealed a higher transconjugation frequency of 1.3 × 10(-4). The conjugation frequency of OXA-48 from K. pneumoniae and E. coli in the gut of low-complexity-microbiota mice was determined to be 2.9 × 10(-5). CONCLUSIONS: The in vivo intergenus gene transfer of OXA-48 in the gut of an infected patient was verified in vitro and in 2 in vivo models, which both showed even higher transmission frequencies vs in vitro conditions. This implies that the current in vitro protocols might not correctly reflect the HGT of carbapenemase genes in vivo.

Pathogenicity of pan-drug-resistant Serratia marcescens harbouring blaNDM-1.

OBJECTIVES: To characterize a pan-drug-resistant Serratia marcescens clinical isolate carrying the New Delhi metallo-ß-lactamase (NDM)-1. METHODS: The presence of ß-lactamase genes was examined by PCR and sequencing. Antibiotic susceptibility was determined by antibiotic gradient test. Transformation assays, transconjugation assays, PFGE and PCR-based replicon typing were used for plasmid analysis. Horizontal gene transfer was evaluated by liquid mating using Escherichia coli J53 as a recipient. Pathogenicity of NDM-1 expressing S. marcescens was analysed using the Galleria mellonella infection model. RESULTS: S. marcescens isolate SM1890 was non-susceptible to all tested antibiotics, with minocycline retaining intermediate activity. blaNDM-1 was located on a 140 kb IncA/C-type plasmid which was transferable to E. coli and Klebsiella pneumoniae by conjugation. The LD50 of the NDM-positive, SM1890 isolate was higher than that of other, NDM-1 negative, S. marcescens strains. CONCLUSIONS: The presence of a blaNDM-1-harbouring IncA/C plasmid resulted in marked resistance to ß-lactam antibiotics, but had no significant effect on virulence of isogenic strains. Because of the intrinsic resistance of S. marcescens to colistin and reduced susceptibility to tigecycline, treatment options for infections by NDM-1-positive isolates are extremely limited in this species.