Sepsis is the leading cause of direct maternal mortality, but there are no data directly comparing the response to sepsis in pregnant and nonpregnant (NP) individuals. This study uses a mouse model of sepsis to test the hypothesis that the cardiovascular response to sepsis is more marked during pregnancy. Female CD1 mice had radiotelemetry probes implanted and were time mated. NP and day 16 pregnant CD-1 mice received intraperitoneal lipopolysaccharide (LPS; 10 μg, serotype 0111: B4). In a separate study, tissue and serum (for RNA, protein and flow cytometry studies), aorta and uterine vessels (for wire myography) were collected after LPS or vehicle control administration. Administration of LPS resulted in a greater fall in blood pressure in pregnant mice compared to NP mice. This occurred with similar changes in the circulating levels of cytokines, vasoactive factors, and circulating leukocytes, but with a greater monocyte and lesser neutrophil margination in the lungs of pregnant mice. Baseline markers of cardiac dysfunction and apoptosis as well as cytokine expression were higher in pregnant mice, but the response to LPS was similar in both groups as was the ex vivo assessment of vascular function. In pregnant mice, nonfatal sepsis is associated with a more marked hypotensive response but not a greater immune response. We conclude that endotoxemia induces a more marked hypotensive response in pregnant compared to NP mice. These changes were not associated with a more marked systemic inflammatory response in pregnant mice, although monocyte lung margination was greater. The more marked hypotensive response to LPS may explain the greater vulnerability to some infections exhibited by pregnant women. Pregnancy enhances LPS-induced hypotension, 2017, Vol. 97, No. 2 Summary SentenceIn pregnant mice, nonfatal sepsis is associated with a more marked hypotensive response but not a greater immune response.

The majority of women with preexisting heart disease can go through pregnancy safely, however, close attention to detail must be paid to avoid potential complications.

No abstract

No abstract

Objective Fetal intracranial hemorrhage (ICH) is associated with an increased risk of perinatal mortality and morbidity. Healthcare professionals often find it challenging to counsel parents due to its rarity and diverse presentation. The aim of this systematic review and meta‐analysis was to investigate the perinatal outcome of fetuses with ICH. Methods MEDLINE, EMBASE, http://ClinicalTrials.gov and The Cochrane Library databases were searched. Inclusion criteria were studies reporting the outcome of fetuses, newborns and infants diagnosed with ICH. The primary outcome was perinatal death (PND), defined as the sum of intrauterine (IUD) and neonatal death (NND). The secondary outcomes were stillbirth, NND, IUD, termination of pregnancy, need for surgery/shunting at birth, cerebral palsy (defined according to the European Cerebral Palsy Network and classified as diplegia, hemiplegia, quadriplegia, dyskinetic or mixed), neurodevelopmental delay and intact survival. All outcomes were explored in the included fetuses with ICH. A subgroup analysis according to the location of the hemorrhage (intra‐axial and extra‐axial) was also planned. Meta‐analysis of proportions was used to combine data, and pooled proportions and their 95% CI were reported. Results Sixteen studies (193 fetuses) were included in the meta‐analysis. PND occurred in 14.6% (95% CI, 7.3–24.0%) of fetuses with ICH. Among liveborn cases, 27.6% (95% CI, 12.5–45.9%) required shunt placement or surgery after birth and 32.0% (95% CI, 22.2–42.6%) had cerebral palsy. Furthermore, 16.7% (95% CI, 8.4–27.2%) of cases had mild neurodevelopmental delay, while 31.1% (95% CI, 19.0–44.7%) experienced severe adverse neurodevelopmental outcome. Normal neurodevelopmental outcome was reported in 53.6% of fetuses. Subgroup analysis according to the location of ICH showed that PND occurred in 13.3% (95% CI, 5.7–23.4%) of fetuses with intra‐axial bleeding and 26.7% (95% CI, 5.3–56.8%) of those with extra‐axial bleeding. In fetuses with intra‐axial hemorrhage, 25.2% (95% CI, 11.0–42.9%) required shunt placement or surgery after birth and 25.5% (95% CI, 15.3–37.2%) experienced cerebral palsy. In fetuses with intra‐axial hemorrhage, mild and severe neurodevelopmental delay was observed in 14.9% (95% CI, 12.0–27.0%) and 32.8% (95% CI, 19.8–47.4%) of cases, respectively, while 53.2% (95% CI, 37.0–69.1%) experienced normal neurodevelopmental outcome. The incidence of mortality and postnatal neurodevelopmental outcome in fetuses with extra‐axial hemorrhage could not be estimated reliably due to the small number of cases. Conclusions Fetuses with a prenatal diagnosis of ICH are at high risk of perinatal mortality and adverse neurodevelopmental outcome. Postnatal shunt placement or surgery was required in 28% of cases and cerebral palsy was diagnosed in approximately one‐third of infants. Due to the rarity of ICH, multicenter prospective registries are warranted to collect high‐quality data. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

ObjectivesThis study aimed to assess contribution of five genes previously known to be involved in cholestatic liver disease in British Bangladeshi and Pakistani people in the United Kingdom as they are an understudied genetic ancestry group with high rates of parental relatedness and disproportionate disease burden.MethodsFive genes (ABCB4, ABCB11, ATP8B1, NR1H4, TJP2) were interrogated by low/mid whole exome sequencing data of 5236 volunteers. Included were non-synonymous or loss of function (LoF) variants with a minor allele frequency <5%. Variants were filtered and annotated. Variants associated with a phenotype or predicted to be likely pathogenic (LP) underwent protein structure and modelling analysis.ResultsOut of 314 non-synonymous variants, 180 fulfilled the inclusion criteria and were heterozygous. 90 were novel and unique to this cohort and not previously reported in the GnomAD database. Of those novel variants, 22 were considered LP and 9 pathogenic. We identified variants associated with gallstone disease (n=31), intrahepatic cholestasis of pregnancy (ICP, n=16), cholangiocarcinoma and cirrhosis (n=2). Fourteen heterozygous novel LoF variants were identified: 7 frameshift, 5 introduction of premature stop codon and 2 splice acceptor variants. A total of 73 variants underwent protein modelling. The study identified 10 variants that resulted in predicted significant structural damage at a protein level, of which 4 were unique to this cohort.ConclusionsThis study identified novel LP and pathogenic variants. We provide further insight into rare variants associated with ICP, cholangiocarcinoma, and gallstone disease. This study highlights the importance of studying diverse ancestry groups in genomic research.WHAT IS KNOWNCholestatic liver diseases encompass a broad range of conditions.Intrahepatic cholestasis of pregnancy (ICP) is the commonest gestational liver disease.Genetic and environmental factors contribute to the aetiology of cholestatic disease.South Asian populations are disproportionally affected.WHAT IS NEW HEREExome sequencing analysis in a British South Asian population discovered new genetic mutations.Pathogenic variants were identified that increase risk to cholestatic liver disease.Novel variants that contribute to ICP were identified.

Our previous work has shown that pregnancy exacerbates the hypotensive response to both infection and LPS. The high levels of progesterone (P4) associated with pregnancy have been suggested to be responsible for the pregnancy-induced changes in the cardiovascular response to infection. Here, we test the hypothesis that P4 supplementation exacerbates the hypotensive response of the maternal cardiovascular to LPS. Female CD1 mice had radiotelemetry probes implanted to measure haemodynamic function non-invasively and were time-mated. From day 14 of pregnancy, mice received either 10mg of P4 or vehicle alone per day and on day 16, intraperitoneal LPS (10µg of serotype 0111:B4) was injected. In two identically treated cohorts of mice, tissue and serum (for RNA, protein studies) were collected at 6 and 12 hours. Administration of LPS resulted in a fall in blood pressure in vehicle treated, but not P4 supplemented mice. This occurred with similar changes in the circulating levels of cytokines, vasoactive factors and in both circulating and tissue inflammatory cell numbers, but with reduced left ventricular expression of cytokines in P4-supplemented mice. However, left ventricular expression of markers of cardiac dysfunction and apoptosis were similar. This study demonstrates that P4 supplementation prevented LPS-induced hypotension in pregnant mice in association with reduced myocardial inflammatory cytokine gene expression. These observations suggest that rather than being detrimental, P4 supplementation has a protective effect on the maternal cardiovascular response to sepsis.

Objectives: Invasive prenatal testing (IPT) by amniocentesis (AMN) and chorionic villus sampling (CVS) are still relative common procedures in centralised fetal diagnostic centres. Beyond safety and efficacy performance accomplished issues, pain perception is a usual concern for patients, may affect the final decision process. The aim of this study was to identify in our population if the number of annual IPTs per operator is associated to patients' pain perception. Methods: In patients scheduled for IPT at our referral centre we prospectively determined the immediate pos procedure pain perception through an analogue pain perception scale 1 to 10. We analysed the association between reported pain perception and the annual number of procedures practiced by each of five operators. Statistical analysis was performed using Kruskal-Wallis and Mann-Whitney U test. A p-value of < 0.05 was considered statistically significant. Results: 431 cases of IPT were practiced between 2018 and 2020. All procedures were performed by a close group of 5 operators. The pregnancy loss rate was 0.5 %. Patients perception of pain was statistically significantly higher when the operator realised less than 19 annual procedures and statistically significantly lower when the operator realised more than 52 annual procedures. Conclusions: Based on our results a minimal annual number of procedures per operator may warrant a low patients pain perception score and we propose it as a new frontier for quality assessment.