p53-dependent Nestin regulation links tumor suppression to cellular plasticity in liver cancer.

The p53 tumor suppressor coordinates a series of antiproliferative responses that restrict the expansion of malignant cells, and as a consequence, p53 is lost or mutated in the majority of human cancers. Here, we show that p53 restricts expression of the stem and progenitor-cell-associated protein nestin in an Sp1/3 transcription-factor-dependent manner and that Nestin is required for tumor initiation in vivo. Moreover, loss of p53 facilitates dedifferentiation of mature hepatocytes into nestin-positive progenitor-like cells, which are poised to differentiate into hepatocellular carcinomas (HCCs) or cholangiocarcinomas (CCs) in response to lineage-specific mutations that target Wnt and Notch signaling, respectively. Many human HCCs and CCs show elevated nestin expression, which correlates with p53 loss of function and is associated with decreased patient survival. Therefore, transcriptional repression of Nestin by p53 restricts cellular plasticity and tumorigenesis in liver cancer.

Screening for Bacterial Vaginosis Prior to Delivery: A Cost-Effectiveness Study.

OBJECTIVE: The objective of this study was to compare the cost and effectiveness of three strategies for screening and/or treating bacterial vaginosis (BV) during pregnancy prior to delivery: (1) the current standard of care was neither test nor treat for BV (Treat None); (2) test all patients for BV at 36 weeks' gestation; treat if positive (Test Treat); and (3) treat all patients undergoing cesarean delivery with intravenous metronidazole at time of surgery (Treat All Cesarean). Effectiveness was defined as avoidance of postpartum surgical site infection (SSI). STUDY DESIGN: A decision analytic cost-effectiveness model was designed from a third-party payer perspective using clinical and cost estimates obtained from the literature, American College of Surgeons National Surgical Quality Improvement Program participant use file (2005-2019), 2019 National Vital Statistics, Medicare costs, and wholesale drug costs. Cost estimates were inflated to 2020 U.S. dollars. For this study, effectiveness was defined as avoidance of postpartum SSIs. RESULTS: The base case analysis that is the current standard of care of not routinely testing and treating patients for BV (Treat None) was the most expensive and least effective strategy, with a mean cost of $59.16 and infection rate of 3.71%. Empirically treating all patients for BV without testing (Treat All Cesarean) was the most effective and the least expensive strategy, with a mean cost of $53.50 and an infection rate of 2.75%. Testing all patients for BV and treating those positive for BV (Test Treat) was also relatively inexpensive and effective, with an infection rate of 2.94% and mean cost of $57.05. Compared with Treat None, we would expect the Treat All Cesarean strategy to reduce the infection rate by 26%. CONCLUSION: These findings suggest that treating pregnant patients with intravenous metronidazole at time of cesarean delivery could be an effective and cost-saving strategy. Testing and treating for BV could also be considered a reasonable strategy, as it has the added benefit of preserving antibiotic stewardship. In no analysis was the standard of care strategy of neither testing nor treating for BV before delivery the preferred strategy. KEY POINTS: · BV colonization may increase surgical site infection risk after cesarean section.. · Treatment of BV before or during delivery may be cost-saving strategies as treatment could prevent costs associated with infection.. · Further study is needed to best balance the risk of surgical site infection with antibiotic stewardship..

Predictors of Breastfeeding among Women Admitted with Severe Preeclampsia Before 34 Weeks.

OBJECTIVE: Patients with severe preeclampsia (sPREX) face barriers to successful breastfeeding (BF), including an increased risk of maternal and newborn complications, prematurity, and low birth weight. Patients with early-onset sPREX (before 34 weeks' gestation) may be at even greater risk, yet there are little data available on factors associated with BF challenges in this population. We describe rates of BF initiation at hospital discharge and BF continuation at postpartum (PP) visit and identify factors associated with BF noninitiation and BF cessation among patients admitted with early-onset sPREX. STUDY DESIGN: Retrospective cohort study of women with sPREX admitted at less than 34 weeks' gestation to a single tertiary center (2013-2019). Demographic, antepartum, and delivery characteristics were evaluated. Factors associated with BF noninitiation at maternal discharge and with BF cessation at routine PP were assessed. Patients with intrauterine or neonatal demise and those missing BF data were excluded. Bivariate statistics were used to compare characteristics and Poisson regression was used to estimate relative risks (RR). RESULTS: Of 255 patients with early-onset sPREX, 228 (89.4%) had BF initiation at maternal hospital discharge. Initiation of BF occurred less frequently among patients with tobacco use in pregnancy (7.5 vs. 37.0%, χ2 p < 0.001, RR: 0.69 [95% confidence interval, CI: 0.52-0.92]). At 6 weeks' PP, 159 of 199 (79.9%) patients had BF continuation. Maternal age under 20 years (1.9 vs. 17.5%, χ2 p = 0.01, RR: 0.36 [95% CI: 0.14-0.91]) and experiencing maternal morbidity (25.2 vs. 45.0%, χ2 p = 0.01, RR: 0.80 [95% CI: 0.66-0.96]) were associated with BF cessation at the PP visit. CONCLUSION: Among patients with early sPREX, tobacco use in pregnancy was associated with noninitiation of BF at discharge, whereas young maternal age and maternal morbidity were associated with cessation of BF by routine PP visit. Further research is needed on how to support BF in this population, especially among patients with these associated factors. KEY POINTS: · Tobacco use was associated with BF noninitiation in patients with early preeclampsia.. · Maternal age < 20 and maternal morbidity were associated with BF cessation by PP visit.. · BF support for patients with risk factors is important for BF success PP..

Maternal morbidity and mortality among patients with cancer at time of delivery.

BACKGROUND: Individuals with cancer during pregnancy are a medically complex patient population that is anticipated to grow. A better understanding of this population and patterns of risk at time of delivery would offer an opportunity for providers to mitigate maternal morbidity. OBJECTIVE: This study aimed to estimate the prevalence in the United States of concurrent cancer diagnoses at time of delivery by cancer type and associated maternal morbidity and mortality. STUDY DESIGN: Using the National Inpatient Sample, we identified delivery-associated hospitalizations between 2007 and 2018. Concurrent cancer diagnoses were classified using the Clinical Classifications Software. Main outcomes included severe maternal morbidity, as defined by the Centers for Disease Control and Prevention indicators, and mortality during delivery hospitalization. We calculated adjusted rates for cancer diagnosis at time of delivery and adjusted odds ratios of severe maternal morbidity and maternal death during hospitalization using survey-weighted multivariable logistic regression models. RESULTS: In this sample of 9,418,761 delivery-associated hospitalizations, 63 per 100,000 deliveries had a concurrent cancer diagnosis (95% confidence interval, 60-66; national weighted estimate, 46,654,042). The most common cancer types were breast cancer (8.4 per 100,000 deliveries), leukemia (8.4 per 100,000 deliveries), Hodgkin lymphoma (7.4 per 100,000 deliveries), non-Hodgkin lymphoma (5.4 per 100,000 deliveries), and thyroid cancer (4.0 per 100,000 deliveries). Patients with cancer were at significantly higher risk for any severe maternal morbidity (adjusted odds ratio, 5.25; 95% confidence interval, 4.73-5.83) and maternal death (adjusted odds ratio, 67.5; 95% confidence interval, 45.1-101.4). Risks of hysterectomy (adjusted odds ratio, 16.92; 95% confidence interval, 13.96-20.52), acute respiratory distress (adjusted odds ratio, 12.76; 95% confidence interval, 9.92-16.42), sepsis (adjusted odds ratio, 11.91; 95% confidence interval, 8.68-16.32), and embolism (adjusted odds ratio, 11.12; 95% confidence interval, 6.94-17.82) were particularly heightened among patients with cancer. Patients with leukemia, specifically, had the highest risk of adverse maternal outcomes (adjusted rate, 113 per 1000 deliveries; 95% confidence interval, 91-135 per 1000) when evaluating risk by cancer type. CONCLUSION: Patients with cancer are at markedly increased risk of maternal morbidity and all-cause mortality during delivery-associated hospitalization. Risk is distributed unevenly within this population, with certain cancer types carrying unique risks for specific morbidity events.

Risk of stillbirth in United States patients with diagnosed intrahepatic cholestasis of pregnancy.

BACKGROUND: Intrahepatic cholestasis of pregnancy is associated with a 4- to 10-fold increase in the risk of stillbirth in the absence of intervention, leading to recommendations for antenatal assessment, ursodiol use, and often preterm or early term delivery. OBJECTIVE: This study aimed to determine whether current management strategies for intrahepatic cholestasis of pregnancy mitigate the elevated risk of stillbirth at a population level. STUDY DESIGN: This was a retrospective cohort study using the 2015-2020 National Readmissions Database, an administrative database developed by the United States Agency for Healthcare Research and Quality. Our study identified delivery hospitalizations, gestational age at delivery, occurrence of intrahepatic cholestasis of pregnancy and stillbirth, and comorbid conditions using the International Classification of Diseases diagnosis and procedure codes. Moreover, this study compared the timing of delivery and stillbirth rates of pregnant patients with intrahepatic cholestasis of pregnancy vs those without intrahepatic cholestasis of pregnancy at the time of delivery hospitalization. RESULTS: This study identified a cohort of 9,987,705 delivery hospitalizations in the National Readmissions Database, corresponding to a weighted national estimate of 18,609,207 births. Of these births, 152,040 (0.8%) were noted to have an intrahepatic cholestasis of pregnancy diagnosis. Patients with an intrahepatic cholestasis of pregnancy diagnosis were older, with small differences in comorbidities, such as a higher rate of gestational diabetes mellitus, than patients without an intrahepatic cholestasis of pregnancy diagnosis at delivery hospitalization. The overall rates of stillbirth were lower among those with intrahepatic cholestasis of pregnancy than among those without intrahepatic cholestasis of pregnancy (252 vs 386 per 100,000 deliveries; risk difference, 133 fewer per 100,000 deliveries; 95% confidence interval, 98-170), a finding that persisted after adjustment for insurance status, socioeconomic factors, and comorbid conditions (risk difference, 160 fewer stillbirths per 100,000 deliveries; 95% confidence interval, 127-194). Furthermore, although patients with intrahepatic cholestasis of pregnancy were more likely to deliver before term than those without intrahepatic cholestasis of pregnancy (30.1% vs 9.3%; P<.001), increased rates of stillbirth were not noted at any point after stratification of the cohort by gestational age at delivery. CONCLUSION: Patients with intrahepatic cholestasis of pregnancy diagnosis codes delivered earlier than those without intrahepatic cholestasis of pregnancy diagnosis codes, but the percentage of births affected by stillbirth was lower, even when stratifying for gestational age at birth. These results may provide reassurance to patients receiving an intrahepatic cholestasis of pregnancy diagnosis that current management does mitigate stillbirth risk in intrahepatic cholestasis of pregnancy.

Effects of prebiotics, probiotics, and synbiotics on the infant gut microbiota and other health outcomes: A systematic review.

The primary aim of this review was to systematically evaluate the literature regarding the effect of pre-, pro-, or synbiotic supplementation in infant formula on the gastrointestinal microbiota. The Cochrane methodology for systematic reviews of randomized controlled trials (RCTs) was employed. Five databases were searched and 32 RCTs (2010-2021) were identified for inclusion: 20 prebiotic, 6 probiotic, and 6 synbiotic. The methods utilized to evaluate gastrointestinal microbiota varied across studies and included colony plating, fluorescence in situ hybridization, quantitative real-time polymerase chain reaction, or tagged sequencing of the 16S rRNA gene. Fecal Bifidobacterium levels increased with supplementation of prebiotics and synbiotics but not with probiotics alone. Probiotic and synbiotic supplementation generally increased fecal levels of the bacterial strain supplemented in the formula. Across all pre-, pro-, and synbiotic-supplemented formulas, results were inconsistent regarding fecal Clostridium levels. Fecal pH was lower with some prebiotic and synbiotic supplementation; however, no difference was seen with probiotics. Softer stools were often reported in infants supplemented with pre- and synbiotics, yet results were inconsistent for probiotic-supplemented formula. Limited evidence demonstrates that pre- and synbiotic supplementation increases fecal Bifidobacterium levels. Future studies utilizing comprehensive methodologies and additional studies in probiotics and synbiotics are warranted.

Energetic eruptions leading to a peculiar hydrogen-rich explosion of a massive star.

Every supernova so far observed has been considered to be the terminal explosion of a star. Moreover, all supernovae with absorption lines in their spectra show those lines decreasing in velocity over time, as the ejecta expand and thin, revealing slower-moving material that was previously hidden. In addition, every supernova that exhibits the absorption lines of hydrogen has one main light-curve peak, or a plateau in luminosity, lasting approximately 100 days before declining. Here we report observations of iPTF14hls, an event that has spectra identical to a hydrogen-rich core-collapse supernova, but characteristics that differ extensively from those of known supernovae. The light curve has at least five peaks and remains bright for more than 600 days; the absorption lines show little to no decrease in velocity; and the radius of the line-forming region is more than an order of magnitude bigger than the radius of the photosphere derived from the continuum emission. These characteristics are consistent with a shell of several tens of solar masses ejected by the progenitor star at supernova-level energies a few hundred days before a terminal explosion. Another possible eruption was recorded at the same position in 1954. Multiple energetic pre-supernova eruptions are expected to occur in stars of 95 to 130 solar masses, which experience the pulsational pair instability. That model, however, does not account for the continued presence of hydrogen, or the energetics observed here. Another mechanism for the violent ejection of mass in massive stars may be required.

The impact of time restricted eating on appetite and disordered eating in adults: A mixed methods systematic review.

This mixed-methods systematic review evaluated the effect of Time Restricted Eating (TRE) on adult participants' experience of hunger, appetite, and disordered eating. PubMed, CINAHL Plus with Full Text, PscyINFO, and Web of Science were searched for quantitative and qualitative original research articles in human adults that had an intervention with a daily eating window of ≤12 h and outcome measures related to hunger, appetite, or disordered eating. Differences in quantitative measures during TRE and qualitative themes were summarized. Qualitative and quantitative data were synthesized by assessing for convergence and divergence. Sixteen studies were included. TRE was associated with higher appetite at bedtime, and lower or unchanged morning fasting appetite. Evening results were mixed. Disordered eating questionnaires were not different as a result of TRE except in one study that found TRE associated with lower hunger. Qualitative themes converged with these findings, however also showed fear of hunger, eating in the absence of hunger, and eating-related stressors. TRE did not result in major changes to appetite or disordered eating symptoms. Bedtime hunger was higher in TRE. Assessment of subtle alterations in eating behavior, such as eating in the absence of hunger, would be beneficial for future research and intervention design.

Sonographic Evaluation of the Placenta in Fontan Patients: A Case Series.

Due to the advancements in pediatric cardiothoracic surgery and medical management, more individuals with congenital heart disease are reaching reproductive age. It is well established that individuals with Fontan circulation are at an increased risk for maternal and fetal adverse outcomes including maternal cardiovascular complications, hypertensive disorders of pregnancy, preterm birth, and fetal growth restriction. Early onset of poor placental health likely related to chronically elevated central venous pressure/low cardiac output inherited to Fontan circulation may play a role in the development of these outcomes. In this case series, we present second-trimester placental imaging findings and pregnancy outcomes of three individuals with Fontan circulation who delivered at a tertiary center in the Southeastern United States.

Medical Student Duty Hours and Shelf Performance: Is There a Correlation?

OBJECTIVE: To date, there is limited information about medical student duty hours, shelf scores, and overall clerkship performance in obstetrics and gynecology (OB/GYN). As a result, we were curious to know whether spending more time in the clinical environment translated to an improved learning experience or, in contrast, translated to decreased study time and worse overall clerkship performance. STUDY DESIGN: A retrospective cohort analysis was performed at a single academic medical center of all medical students on the OB/GYN clerkship from August 2018 to June 2019. Recorded student duty hours were tabulated per day and per week, by student. National Board of Medical Examiners (NBME) Subject Exam (Shelf) equated percentile scores for the quarter of year were used. RESULTS: Our statistical analysis showed that working long hours did not translate to higher or lower shelf score, or higher overall clerkship grade. However, working longer hours in the last 2 weeks of the clerkship was associated with high shelf score. CONCLUSION: Longer medical student duty hours did not correlate to higher shelf scores or overall clerkship grades. Future multicenter studies are necessary to evaluate the importance of medical student duty hours and continue optimizing the educational experience of the OB/GYN clerkship. KEY POINTS: · Clinical hours were not associated with shelf examination scores.. · Clinical hours were not associated with overall clerkship grade.. · Longer clinical hours at the end of clerkship are correlated with higher examination scores..

Best Practices for Writing Letters of Recommendation for Maternal-Fetal Medicine Fellowship: An Empty Scoping Review.

OBJECTIVES: Though letters of recommendation (LOR) for Maternal-Fetal Medicine (MFM) fellowship are a critical part of application process, little is known regarding best practices for writing them. This scoping review sought to identify published data outlining best practices in writing MFM fellowship LOR. STUDY DESIGN: Scoping review conducted using Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) and JBI guidelines. MEDLINE, Embase, Web of Science, and ERIC were searched, by professional medical librarian using database-specific controlled vocabulary and keywords representing MFM, fellowship, as well as personnel selection, academic performance, examinations, or clinical competence in 4/22. Prior to execution, the search was peer reviewed by another professional medical librarian using the Peer Review Electronic Search Strategies (PRESS) checklist. Citations imported to Covidence, dual screened by authors with disagreements resolved by discussion, and extraction performed by one author and checked by the second. RESULTS: A total of 1,154 studies were identified, with 162 removed as duplicates. Of the 992 screened, 10 imported for full-text review. None of these met inclusion criteria; four were not about fellows and six did not report on best practices for writing LOR for MFM. CONCLUSION: No articles were identified that outlined best practices for writing LOR for MFM fellowship. The lack of guidance and published data guiding those writing LOR for MFM fellowship applicants is concerning given the importance of these as a tool used by fellowship directors in selecting applicants for interviews and ranking. KEY POINTS: · No published articles were identified addressing best practices for writing LOR for MFM fellowship.. · Fellowship directors rely on LOR for offering interviews and rank list.. · Future research is urgently needed to identify best practices..

Preterm Birth Rates and Racial Disparities during the COVID-19 Pandemic at a Single Institution in the Southeastern United States.

OBJECTIVE: The COVID pandemic has been associated with varied effects on preterm birth (PTB). We sought to compare rates of PTB during the pre- and post vaccination COVID periods with pre-pandemic PTB rates, stratified by race and ethnicity. STUDY DESIGN: Retrospective cohort comparing all deliveries over 20 weeks at a single tertiary center during "early" (March 2020-June 2020) versus "late" COVID (March 2021-June 2021), and "late" COVID versus pre-COVID (March to June 2014-2019). PTBs <37, <34, and <28 weeks were compared and stratified by race/ethnicity. RESULTS: A total of 16,483 deliveries occurred including 2,068 "early" COVID, 2,115 "late" COVID, and 12,300 pre-COVID. The PTB rate during "late" COVID was lower compared to "early" COVID (12.1 vs. 14.6%, p = 0.02). Rate of PTB <34 was also lower during "late" COVID (4.4 vs. 5.7%, p = 0.05). PTB <28 did not differ. When controlling for prior PTB, "late" COVID remained associated with a decreased risk of PTB compared to "early" COVID, adjusted odds ratio (aOR) of 0.82 (95% confidence interval [CI]: 0.68, 0.98). Although there was no difference in PTB among Hispanic individuals when comparing "late" COVID versus pre-COVID, when further subdivided, a small number of Hispanic Puerto Rican individuals had higher odds of PTB < 37 during "late" COVID versus pre-COVID (aOR = 4.29 [95% CI: 1.12, 16.4]). Additionally, White individuals had reduced odds of PTB <37 (aOR = 0.80 [95% CI: 0.65, 0.98]) during "late" COVID versus pre-COVID while the PTB rate was unchanged when comparing "late" COVID versus pre-COVID in all other racial and ethnic groups. CONCLUSION: During 2021, PTB rates decreased from rates observed in 2020 at the height of COVID restrictions. Among White birthing individuals, PTB decreased in 2021 compared to pre-COVID rates. This decrease was not observed in Black and Hispanic birthing individuals. These data highlight the continued racially disparate impact of the COVID-19 pandemic on PTB rates. KEY POINTS: · The COVID-19 pandemic has been associated with varied effects on the preterm birth (PTB) rate.. · PTB rates decreased in "late" COVID compared to "early" COVID.. · When stratified, PTB decreased among white individuals, but not in Black or Hispanic individuals..

Sex-Dependent Differences in Mouse Placental Gene Expression following a Maternal High-Fat Diet.

OBJECTIVE: In utero fetal exposures may have sex-specific placental gene responses. Our objective was to measure sex-based differences in placental gene expression from dams fed high-fat diet (HFD) versus control diet (CD). STUDY DESIGN: We fed timed pregnant Friend virus B-strain dams either a CD (n = 5) or an HFD (n = 5). We euthanized dams on embryonic day 17.5 to collect placentas. We extracted placental RNA and hybridized it to a customized 96-gene Nanostring panel focusing on angiogenic, inflammatory, and growth genes. We compared normalized gene expression between CD and HFD, stratified by fetal sex, using analysis of variance. Pathway analysis was used to further interpret the genomic data. RESULTS: Pups from HFD-fed dams were heavier than those from CD-fed dams (0.97 ± 0.06 vs 0.84 ± 0.08 g, p < 0.001). Male pups were heavier than females in the HFD (0.99 ± 0.05 vs 0.94 ± 0.06 g, p = 0.004) but not CD (0.87 ± 0.08 vs 0.83 ± 0.07 g, p = 0.10) group. No sex-based differences in placental gene expression in CD-fed dams were observed. Among HFD-fed dams, placentas from female pups exhibited upregulation of 15 genes (q = 0.01). Network analyses identified a cluster of genes involved in carbohydrate metabolism, cellular function and maintenance, and endocrine system development and function (p = 1 × 10-23). The observed female-specific increased gene expression following in utero HFD exposure was predicted to be regulated by insulin (p = 5.79 × 10-13). CONCLUSION: In female compared with male pups, in utero exposure to HFD upregulated placental gene expression in 15 genes predicted to be regulated by insulin. Sex-specific differences in placental expression of these genes should be further investigated. KEY POINTS: · Male pups were heavier than female pups at the time of sacrifice when dams were fed an HFD.. · HFD was associated with upregulated gene expression in female placentas.. · Female-specific increased gene was predicted to be regulated by insulin..

Predictors of Breastfeeding among Patients Admitted with Preterm Prelabor Rupture of Membranes.

OBJECTIVE: We sought to describe rates of breastmilk feeding (BF) at hospital discharge and 6 weeks postpartum and to identify risk factors for noninitiation or cessation among pregnancies complicated by preterm prelabor rupture of membranes (PPROM). STUDY DESIGN: Retrospective cohort study of pregnant persons with PPROM admitted to a single tertiary center (2013-2019). Patients with deliveries complicated by intrauterine or neonatal demise or with incomplete BF data were excluded. Demographic, antepartum, and delivery characteristics were evaluated. Primary analysis identified rate of BF initiation at maternal discharge and factors associated with noninitiation. Secondary analysis evaluated BF continuation and factors associated with cessation at 6 weeks postpartum. Bivariate statistics were used to compare characteristics and logistic regression was used to estimate adjusted odds ratios (aOR). RESULTS: Of 397 patients with PPROM, 342(86%) initiated BF prior to discharge. Those reporting tobacco use in pregnancy were less likely to initiate BF (aOR: 0.32; 95% confidence interval [CI]: 0.16, 0.64). In contrast, private insurance (aOR: 2.53; 95% CI: 1.19, 5.37) and pregnancy latency ≥ 14 days (aOR: 3.02; 95% CI: 1.09, 8.38) were associated with BF initiation at hospital discharge. Of the 293 patients with postpartum follow-up, only 214 (73%) had BF continuation at 6 weeks postpartum. Maternal age <20 years (aOR: 0.07; 95% CI: 0.01, 0.68) and multiparity (aOR: 0.54; 95% CI: 0.29, 0.99) were associated with BF cessation. Patients with private insurance were observed to have increased odds of BF continuation (aOR: 2.10; 95% CI: 1.07, 4.12). CONCLUSION: Among patients with PPROM, tobacco use may be associated with noninitiation of BF prior to discharge, whereas age < 20 years and multiparity were associated with cessation by 6 weeks postpartum. Longer pregnancy latency ≥ 14 days was associated with BF initiation prior to discharge. Private insurance was associated with increased rates of BF initiation and continuation postpartum. BF education and support should be offered to all patients admitted for PPROM. KEY POINTS: · Tobacco use may be associated with BF noninitiation.. · Young age and multiparity are linked with BF cessation.. · Private insurance resulted in BF initiation and continuation..

Associations between Anemia and Outcomes of Pregnant Patients with Pyelonephritis.

OBJECTIVE: This study aims to determine if pregnant patients with both pyelonephritis and anemia are at an increased risk of adverse maternal outcomes compared with those with pyelonephritis without anemia. STUDY DESIGN: We conducted a retrospective cohort study utilizing the Nationwide Readmissions Database (NRD). Patients with antepartum pyelonephritis-associated hospitalizations from October 2015 to December 2018 were included. International Classification of Diseases codes were used to identify pyelonephritis, anemia, maternal comorbidities, and severe maternal morbidities. The primary outcome was a composite of severe maternal morbidity, as defined by the Centers for Disease Control criteria. Univariate statistical methods, weighted to account for complex survey methods in the NRD, were used to assess for associations between anemia, baseline characteristics, and patient outcomes. Weighted logistic and Poisson regressions were used to assess for associations between anemia and outcomes, adjusting for clinical comorbidities and other confounding factors. RESULTS: In total, 29,296 pyelonephritis admissions were identified, corresponding to a weighted national estimate of 55,135 admissions. Of these, 11,798 (21.3%) were anemic. The rate of severe maternal morbidity was higher among anemic patients than nonanemic patients (27.8% vs. 8.9%, respectively, p < 0.001), and remained higher after adjustment (adjusted relative risk [aRR] 2.86 [95% confidence interval [CI]: 2.67, 3.06]). Rates of individual components of severe maternal morbidities, including acute respiratory distress syndrome (4.0% vs. 0.6%, aRR 3.97 [95% CI: 3.10, 5.08]), sepsis (22.5% vs. 7.9%, aRR 2.64 [95% CI: 2.45, 2.85]), shock (4.5% vs. 0.6%, aRR 5.48 [95% CI: 4.32, 6.95]), and acute renal failure (2.9% vs. 0.8%, aRR 1.99 [95% CI: 1.55, 2.55]) were all higher for anemic pyelonephritis. The mean length of stay was also longer (25% average increase, 95% CI: 22%, 28%). CONCLUSION: Among pregnant patients with pyelonephritis, those with anemia are at greater risk of severe maternal morbidity and longer hospital stay. KEY POINTS: · Anemia is associated with longer stays for pyelo.. · Anemic pyelo patients have increased morbidity.. · Anemic pyelo patients have increased sepsis risk..

Risk Factors for Adverse Maternal Outcomes among Patients with Severe Preeclampsia Before 34 Weeks.

OBJECTIVE: This study aimed to characterize rates of maternal morbidity associated with early (<34 wk) preeclampsia with severe features and to determine factors associated with developing these morbidities. STUDY DESIGN: Retrospective cohort study of patients with early preeclampsia with severe features at a single institution from 2013 to 2019. Inclusion criteria were admission between 23 and 34 weeks and diagnosis of preeclampsia with severe features. Maternal morbidity defined as death, sepsis, intensive care unit (ICU) admission, acute renal insufficiency (acute kidney injury [AKI]), postpartum (PP) dilation and curettage, PP hysterectomy, venous thromboembolism (VTE), PP hemorrhage (PPH), PP wound infection, PP endometritis, pelvic abscess, PP pneumonia, readmission, and/or need for blood transfusion. Death, ICU admission, VTE, AKI, PP hysterectomy, sepsis, and/or transfusion of >2 units were considered severe maternal morbidity (SMM). Simple statistics used to compare characteristics among patients experiencing any morbidity and those not. Poisson regression used to assess relative risks. RESULTS: Of 260 patients included, 77 (29.6%) experienced maternal morbidity and 16 (6.2%) experienced severe morbidity. PPH (n = 46, 17.7%) was the most common morbidity, although 15 (5.8%) patients were readmitted, 16 (6.2%) needed a blood transfusion, and 14 (5.4%) had AKI. Patients who experienced maternal morbidity were more likely to be advanced maternal age, have preexisting diabetes, have multiples, and deliver nonvaginally (all ps < 0.05). Diagnosis of preeclampsia < 28 weeks or longer latency from diagnosis to delivery were not associated with increased maternal morbidity. In regression models, the relative risk of maternal morbidity remained significant for twins (adjusted odds ration [aOR]: 2.57; 95% confidence interval [CI]: 1.67, 3.96) and preexisting diabetes (aOR: 1.64; 95% CI: 1.04, 2.58), whereas attempted vaginal delivery was protective (aOR: 0.53; 95% CI: 0.30, 0.92). CONCLUSION: In this cohort, more than 1 in 4 patients diagnosed with early preeclampsia with severe features experienced maternal morbidity, whereas 1 in 16 patients experienced SMM. Twins and pregestational diabetes were associated with higher risk of morbidity, whereas attempted vaginal delivery was protective. These data may be helpful in promoting risk reduction and counseling patients diagnosed with early preeclampsia with severe features. KEY POINTS: · One in four patients diagnosed with preeclampsia w/ severe features experienced maternal morbidity.. · One in 16 patients with preeclampsia w/ severe features experienced severe maternal morbidity.. · Factors most associated with morbidity/severe morbidity were twins and pregestational diabetes.. · Patients who attempted vaginal delivery appeared to have a lower rate of morbidity..

Does acute funisitis predict worse neonatal outcomes among term newborns?

BACKGROUND: Acute funisitis-the histologic diagnosis of inflammation within the umbilical cord-represents a fetal inflammatory response to infection. Although acute funisitis has been associated with an increased risk of adverse outcomes among preterm neonates, there are limited and conflicting data with term deliveries. OBJECTIVE: This study aimed to evaluate the association between acute funisitis and neonatal morbidity in neonates born at term to pregnant patients with a clinical diagnosis of intraamniotic infection. STUDY DESIGN: This was a retrospective cohort study of pregnant patients who had clinically diagnosed intraamniotic infection at term, delivered vaginally at a single tertiary institution from 2013 to 2019, and had histologic chorioamnionitis on placental pathology. Patients with intrauterine fetal demise or missing neonatal/placental pathology data were excluded. The primary outcome was a neonatal sepsis composite, defined as culture-positive bacteremia, neutropenia (absolute neutrophil count<3500/µL), or immature-to-total neutrophil ratio>0.2. The secondary outcomes included composite neonatal morbidity, defined as neonatal intensive care unit admission, 5-minute Apgar score <7, bacteremia, endotracheal intubation or need for continuous positive airway pressure, intraventricular hemorrhage (grade 3 or 4), necrotizing enterocolitis (stage 3 or 4), umbilical artery pH<7.1, umbilical artery base excess>12, and neonatal mortality. The components of these composites, neonatal intensive care unit length of stay, and Kaiser early-onset sepsis score were also measured. Neonates with acute funisitis on pathology were compared with those without acute funisitis using bivariate statistics. Regression was used to estimate the relative risk of outcomes. RESULTS: Of 184 neonates with deliveries complicated by intraamniotic infection, acute funisitis was present in 109 (59%) placental specimens. Composite neonatal sepsis was significantly higher among neonates with acute funisitis (relative risk, 1.85; 95% confidence interval, 1.13-3.03) than in those without acute funisitis. As a marker for sepsis, acute funisitis has a sensitivity of 39.4%, negative predictive value of 47.2%, specificity of 78.7%, and positive predictive value of 72.9%. An immature-to-total neutrophil ratio>0.2 (relative risk, 1.83; 95% confidence interval, 1.09-3.08) was also significantly associated with acute funisitis. Neonatal morbidity composite, intraventricular hemorrhage, necrotizing enterocolitis, neonatal intensive care unit admission, higher Kaiser early-onset sepsis scores, and other examined outcomes were not statistically associated with acute funisitis. CONCLUSION: In term deliveries complicated by intraamniotic infection, acute funisitis was associated with increased neonatal sepsis. Current approaches for estimating neonatal sepsis risk are limited by their reliance on indirect maternal factors such as maximum maternal temperature and intrapartum antibiotic use. This study suggests that acute funisitis may serve as a marker that could be utilized to augment risk stratification at birth if a protocol for evaluating the umbilical cord in real-time were widely adopted.

Incidence and Risk Factors for Postpartum Depression among Women with Preterm Prelabor Rupture of Membranes.

OBJECTIVE: Patients admitted for preterm prelabor rupture of membranes are more likely to have risk factors for postpartum depression, including preterm delivery, low-birthweight infants, and a stressful life event. However, there is a paucity of data characterizing the development of postpartum depression in this population. We aim to evaluate the incidence of and describe risk factors for postpartum depression among patients admitted with preterm prelabor rupture of membranes. STUDY DESIGN: This is a retrospective cohort study of patients admitted for preterm prelabor rupture of membranes in a single health system between 2013 and 2019. Patients who developed depression were compared with patients who did not develop depression. Demographic, antepartum/intrapartum/postpartum, and neonatal characteristics were compared. Bivariate statistics were used to compare outcomes and logistic regression was used to estimate adjusted odds ratios. RESULTS: Of 132 included patients with preterm prelabor rupture of membranes, 25 (18.9%) had postpartum depression. Factors significantly (p < 0.05) associated with postpartum depression included history of depression, anxiety, or any prior mental health condition. Earlier admission gestational age, rupture of membranes < 28 weeks, earlier delivery gestational age, neonatal morbidity, and neonatal necrotizing enterocolitis also were significantly associated with postpartum depression. Latency, maternal postpartum length of stay, and neonatal intensive care unit length of stay were not significantly associated. In regression models, only a history of depression (odds ratio [OR], 11.89; 95% confidence interval [CI], 2.78-50.95) and neonatal morbidity (OR, 5.01; 95% CI, 1.15-21.89) remained associated with postpartum depression. CONCLUSION: Postpartum depression occurred in nearly one in five patients with preterm prelabor rupture of membranes. Pre-existing depression and adverse neonatal outcomes strongly predicted postpartum depression. There is an urgent need to prioritize maternal mental health among patients with preterm prelabor rupture of membranes in the peripartum period. Further research is needed to identify optimal resources for mitigating the risk of postpartum depression in this cohort. KEY POINTS: · After PPROM, postpartum depression is common.. · Maternal depression and neonatal morbidity are risk factors for PPD.. · Hospital admission permits intervention for PPD..

Pregnancy Outcomes among Women with Class III Obesity with Pre-diabetic Early Hemoglobin A1C.

OBJECTIVE: We aimed to assess the risk of developing gestational diabetes mellitus (GDM) in women with a normal A1C (<5.7) compared with those with an A1C in the pre-diabetic range (5.7-6.4). STUDY DESIGN: This study comprises of a retrospective cohort of non-anomalous singleton pregnancies with maternal body mass index (BMI) ≥40 at a single institution from 2013 to 2017. Pregnancies with multiple gestation, late entry to care, type 1 or 2 diabetes, and missing diabetes-screening information were excluded. The primary outcome was development of GDM. Secondary outcomes included fetal growth restriction, macrosomia, gestational age at delivery, large for gestational age, delivery BMI at delivery, total weight gain in pregnancy, induction of labor, shoulder dystocia, and cesarean delivery. Bivariate statistics were used to compare demographics, pregnancy complications, and delivery characteristics of women who had an early A1C < 5.7 and A1C 5.7 to 6.4. Multivariable analyses were used to estimate the odds of the primary outcome. RESULTS: Eighty women (68%) had an early A1C <5.7 and 38 (32%) had a A1C 5.7 to 6.4. Women in the lower A1C group were less likely to be Black (45 vs. 74%, p = 0.01). No differences in other baseline demographics were observed. The median A1C was 5.3 for women with A1C < 5.7 and 5.8 for women with A1C 5.7 to 6.4 (p < 0.001). GDM was significantly more common in women with A1C 5.7 to 6.4 (3.8 vs. 24%, p = 0.002). Women with pre-diabetic range A1C had an odd ratio of 11.1 (95% CI 2.49-48.8) for GDM compared with women with a normal A1C. CONCLUSION: Women with class III obesity and a pre-diabetic range A1C are at an increased risk for gestational diabetes when compared with those with a normal A1C in early pregnancy. KEY POINTS: · One in 3 women with class III obesity had a pre-diabetic range early A1C.. · Class III obese women who have a pre-diabetic A1C have a higher risk of gestational diabetes.. · In this high-risk population, early A1C results in the pre-diabetic range are associated with higher rates of gestational diabetes..