Preliminary Findings of mRNA Covid-19 Vaccine Safety in Pregnant Persons.

BACKGROUND: Many pregnant persons in the United States are receiving messenger RNA (mRNA) coronavirus disease 2019 (Covid-19) vaccines, but data are limited on their safety in pregnancy. METHODS: From December 14, 2020, to February 28, 2021, we used data from the "v-safe after vaccination health checker" surveillance system, the v-safe pregnancy registry, and the Vaccine Adverse Event Reporting System (VAERS) to characterize the initial safety of mRNA Covid-19 vaccines in pregnant persons. RESULTS: A total of 35,691 v-safe participants 16 to 54 years of age identified as pregnant. Injection-site pain was reported more frequently among pregnant persons than among nonpregnant women, whereas headache, myalgia, chills, and fever were reported less frequently. Among 3958 participants enrolled in the v-safe pregnancy registry, 827 had a completed pregnancy, of which 115 (13.9%) resulted in a pregnancy loss and 712 (86.1%) resulted in a live birth (mostly among participants with vaccination in the third trimester). Adverse neonatal outcomes included preterm birth (in 9.4%) and small size for gestational age (in 3.2%); no neonatal deaths were reported. Although not directly comparable, calculated proportions of adverse pregnancy and neonatal outcomes in persons vaccinated against Covid-19 who had a completed pregnancy were similar to incidences reported in studies involving pregnant women that were conducted before the Covid-19 pandemic. Among 221 pregnancy-related adverse events reported to the VAERS, the most frequently reported event was spontaneous abortion (46 cases). CONCLUSIONS: Preliminary findings did not show obvious safety signals among pregnant persons who received mRNA Covid-19 vaccines. However, more longitudinal follow-up, including follow-up of large numbers of women vaccinated earlier in pregnancy, is necessary to inform maternal, pregnancy, and infant outcomes.

Birth Outcomes Among People with Hepatitis C in Pregnancy - Three U.S. States, 2018-2021.

INTRODUCTION: There are limited and conflicting data regarding the impact of hepatitis C in pregnancy on adverse birth outcomes. METHODS: Using the Surveillance for Emerging Threats to Pregnant People and Infants Network (SET-NET), a large surveillance cohort, we describe birth outcomes among a cohort of people with HCV in pregnancy in total and by reported substance use. RESULTS: Among 1418 infants, 89% were born to people with reported substance use during pregnancy. The proportion born preterm was 20%, 13% were small-for-gestational age and 34% of term infants required intensive care. CONCLUSIONS: Assessments of recent changes to recommendations for HCV screening in pregnancy should evaluate the impact on maternal access to care for both HCV treatment as well as comorbidities such as substance use disorder which may contribute to adverse birth outcomes.

Treatment of hypoplastic left heart syndrome: a systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: This meta-analysis aimed to consolidate existing data from randomised controlled trials on hypoplastic left heart syndrome. METHODS: Hypoplastic left heart syndrome specific randomised controlled trials published between January 2005 and September 2021 in MEDLINE, EMBASE, and Cochrane databases were included. Regardless of clinical outcomes, we included all randomised controlled trials about hypoplastic left heart syndrome and categorised them according to their results. Two reviewers independently assessed for eligibility, relevance, and data extraction. The primary outcome was mortality after Norwood surgery. Study quality and heterogeneity were assessed. A random-effects model was used for analysis. RESULTS: Of the 33 included randomised controlled trials, 21 compared right ventricle-to-pulmonary artery shunt and modified Blalock-Taussig-Thomas shunt during the Norwood procedure, and 12 regarded medication, surgical strategy, cardiopulmonary bypass tactics, and ICU management. Survival rates up to 1 year were superior in the right ventricle-to-pulmonary artery shunt group; this difference began to disappear at 3 years and remained unchanged until 6 years. The right ventricle-to-pulmonary artery shunt group had a significantly higher reintervention rate from the interstage to the 6-year follow-up period. Right ventricular function was better in the modified Blalock-Taussig-Thomas shunt group 1-3 years after the Norwood procedure, but its superiority diminished in the 6-year follow-up. Randomised controlled trials regarding medical treatment, surgical strategy during cardiopulmonary bypass, and ICU management yielded insignificant results. CONCLUSIONS: Although right ventricle-to-pulmonary artery shunt appeared to be superior in the early period, the two shunts applied during the Norwood procedure demonstrated comparable long-term prognosis despite high reintervention rates in right ventricle-to-pulmonary artery shunt due to pulmonary artery stenosis. For medical/perioperative management of hypoplastic left heart syndrome, further randomised controlled trials are needed to deliver specific evidence-based recommendations.

Alcohol Use, Screening, and Brief Intervention Among Pregnant Persons - 24 U.S. Jurisdictions, 2017 and 2019.

Alcohol use during pregnancy is a major preventable cause of adverse alcohol-related outcomes, including birth defects and developmental disabilities.* Alcohol screening and brief intervention (ASBI) is an evidence-based primary care tool that has been shown to prevent or reduce alcohol consumption during pregnancy; interventions have resulted in an increase in the proportion of pregnant women reporting abstinence (odds ratio = 2.26; 95% CI = 1.43-3.56) (1). Previous national estimates have not characterized ASBI in populations of pregnant persons. Using 2017 and 2019 Behavioral Risk Factor Surveillance System (BRFSS) data, CDC examined prevalence of ASBI and characteristics of pregnant persons and nonpregnant women aged 18-49 years (reproductive-aged women) residing in jurisdictions that participated in the BRFSS ASBI module. During their most recent health care visit within the past 2 years, approximately 80% of pregnant persons reported being asked about their alcohol use; however, only 16% of pregnant persons who self-reported current drinking at the time of the survey (at least one alcoholic beverage in the past 30 days) were advised by a health care provider to quit drinking or reduce their alcohol use. Further, the prevalence of screening among pregnant persons who did not graduate from high school was lower than that among those who did graduate from high school or had at least some college education. This gap between screening and brief intervention, along with disparities in screening based on educational level, indicate missed opportunities to reduce alcohol use during pregnancy. Strategies to enhance ASBI during pregnancy include integrating screenings into electronic health records, increasing reimbursement for ASBI services, developing additional tools, including electronic ASBI, that can be implemented in a variety of settings (2,3).

Systematic Review: Polysubstance Prevalence Estimates Reported during Pregnancy, US, 2009-2020.

INTRODUCTION: The objective of this systematic review is to describe polysubstance studies and their prevalence estimates among pregnant people in the US. METHODS: This review was not subject to protocol preparation or registration with the International Prospective Register of Systematic Reviews (PROSPERO) because outcome data were not reported. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Checklist was followed. Four scientific literature databases were used to identify articles published from January 1, 2009 to June 3, 2020 reporting prenatal exposure to two or more substances in the US. A standardized process of title and abstract screening followed by a two-phase full-text review was used to assess study eligibility. RESULTS: A total of 119 studies were included: 7 case-control studies, 7 clinical trials, 76 cohort studies, and 29 cross-sectional studies. Studies varied with respect to study design, time period, region, sampling and participant selection, substances assessed, and method of exposure ascertainment. Commonly reported polysubstance prevalence estimates among studies of pregnant people included combinations with alcohol, marijuana, and/or tobacco/nicotine. The range of prevalence estimates was wide (alcohol 1-99%; marijuana 3-95%; tobacco/nicotine 2-95%). DISCUSSION: Polysubstance use during pregnancy is common, especially with alcohol, marijuana, and/or tobacco/nicotine. Future research to assess polysubstance use during pregnancy could help better describe patterns and ultimately help mitigate its effects on maternal and infant health outcomes.

Screening and Brief Interventions for Alcohol Use During Pregnancy: Practices Among US Primary Care Clinicians, DocStyles 2019.

INTRODUCTION: Alcohol use during pregnancy can cause birth defects and developmental disabilities. From 2018 through 2020, 13.5% of pregnant women reported current drinking. The US Preventive Services Task Force recommends evidence-based tools (eg, AUDIT-C and SASQ) for implementing screening and brief interventions to reduce excessive alcohol use among adults, including pregnant people, for whom any alcohol use is considered excessive. METHODS: We used DocStyles 2019 data to conduct a cross-sectional analysis to examine current screening and brief intervention practices that primary care clinicians conduct among pregnant patients; clinicians' confidence levels in conducting screening, brief interventions, and referral to treatment; and the documentation of brief interventions in the medical record. RESULTS: A total of 1,500 US adult medicine clinicians completed the entire survey. Among the respondents who conduct screening (N = 1,373) and brief interventions (N = 1,357) in their practice, nearly all reported implementing screening (94.6%) and brief interventions (94.9%) with their pregnant patients for alcohol use, but fewer than half felt confident about conducting their screening practices (46.5%). Two-thirds (64%) reported using a tool that met the criteria recommended by the US Preventive Services Task Force (USPSTF). Over half documented brief interventions in electronic health record notes (51.7%) or designated space (50.7%). CONCLUSION: Pregnancy presents a unique opportunity for clinicians to incorporate screening into routine obstetric care and encourage behavior change among patients. Most providers reported always screening their pregnant patients for alcohol use, but fewer used evidence-based USPSTF-recommended screening tools. Increased clinician confidence in screening and brief intervention, the use of standardized screening tools tailored to pregnant people, and maximal use of electronic health record technology may enhance the benefits of their application to alcohol use, which ultimately can reduce adverse outcomes associated with alcohol use during pregnancy.

Characterization of rhodanine derivatives as potential disease-modifying drugs for experimental mouse osteoarthritis.

OBJECTIVE: This study was performed to characterize selected rhodanine derivatives as potential preclinical disease-modifying drugs for experimental osteoarthritis (OA) in mice. METHODS: Three rhodanine derivatives, designated rhodanine (R)-501, R-502, and R-503, were selected as candidate OA disease-modifying drugs. Their effects were evaluated by intra-articular (IA) injection in OA mouse models induced by DMM (destabilization of the medial meniscus) or adenoviral overexpression in joint tissues of hypoxia-inducible factor (HIF)-2α or zinc importer ZIP8. The regulatory mechanisms impacted by the rhodanine derivatives were examined in primary-culture chondrocytes and fibroblast-like synoviocytes (FLS). RESULTS: All three rhodanine derivatives inhibited OA development caused by DMM or overexpression of HIF-2α or ZIP8. Compared to vehicle-treated group, for example, IA injection of R-501 in DMM-operated mice reduced median OARSI grade from 3.78 (IQR 3.00-5.00) to 1.89 (IQR 0.94-2.00, P = 0.0001). R-502 and R-503 also reduced from 3.67 (IQR 2.11-4.56) to 2.00 (IQR 1.00-2.00, P = 0.0030) and 2.00 (IQR 1.83-2.67, P = 0.0378), respectively. Mechanistically, the rhodanine derivatives inhibited the nuclear localization and transcriptional activity of HIF-2α in chondrocytes and FLS. They did not bind to Zn2+ or modulate Zn2+ homeostasis in chondrocytes or FLS; instead, they inhibited the nuclear localization and transcriptional activity of the Zn2+-dependent transcription factor, MTF1. HIF-2α, ZIP8, and interleukin-1ß could upregulate matrix-degrading enzymes in chondrocytes and FLS, and the rhodanine derivatives inhibited these effects. CONCLUSION: IA administration of rhodanine derivatives significantly reduced OA pathogenesis in various mouse models, demonstrating that these derivatives have disease-modifying therapeutic potential against OA pathogenesis.

Universal Early Coarsening of Quenched Bose Gases.

We investigate the early coarsening dynamics of an atomic Bose gas quenched into a superfluid phase. Using a two-step quench protocol, we independently control the two cooling rates during and after passing through the critical region, respectively, and measure the number of quantum vortices spontaneously created in the system. The latter cooling rate regulates the temperature during the condensate growth, consequently controlling the early coarsening dynamics in the defect formation. We find that the defect number shows a scaling behavior with the latter cooling rate regardless of the initial cooling rate, indicating universal coarsening dynamics in the early stage of condensate growth. Our results demonstrate that early coarsening not only reduces the defect density, but also affects its scaling with the quench rate, which is beyond the Kibble-Zurek mechanism.

Alcohol Consumption and Binge Drinking During Pregnancy Among Adults Aged 18-49 Years - United States, 2018-2020.

There is no known safe amount of alcohol consumption during pregnancy; drinking alcohol during pregnancy can cause fetal alcohol spectrum disorders and might increase the risk for miscarriage and stillbirth (1). The prevalence of drinking among pregnant women increased slightly during 2011-2018; however, more recent estimates are not yet reported (2). CDC estimated the prevalence of self-reported current drinking (at least one alcoholic drink in the past 30 days) and binge drinking (consuming four or more drinks on at least one occasion in the past 30 days) among pregnant adults aged 18-49 years, overall and by selected characteristics, using 2018-2020 Behavioral Risk Factor Surveillance System (BRFSS) data. During 2018-2020, 13.5% of pregnant adults reported current drinking and 5.2% reported binge drinking: both measures were 2 percentage points higher than during 2015-2017. Pregnant adults with frequent mental distress were 2.3 and 3.4 times as likely to report current and binge drinking, respectively, compared with those without frequent mental distress. In addition, pregnant adults without a usual health care provider were 1.7 times as likely to report current drinking as were those with a current provider. Alcohol consumption during pregnancy continues to be a serious problem. Integration of mental health services into clinical care and improving access to care might help address alcohol consumption and mental distress during pregnancy to prevent associated adverse outcomes (3).

Environmental risk factors for inflammatory bowel disease: A case control study in Southeast Asian children.

AIM: Early-life environmental exposure, which has important implications in the pathogenesis of inflammatory bowel disease (IBD), is not well understood in Asian children. We examined environmental factors prior to the development of childhood IBD in a Southeast Asian population. METHODS: We conducted a case control study in IBD diagnosed before 18 years of age and controls matched by gender, age and ethnicity. A questionnaire recording medical, family, dietary and social histories, home environment, childhood diseases and immunisation status was used. RESULTS: In a multivariate analysis involving 70 children with IBD (Crohn's disease (CD) = 38; ulcerative colitis (UC) = 32) and 140 controls, childhood acute gastroenteritis (odds ratio (OR): IBD 6.9; CD 7.8; UC 5.8) and excessive antibiotic usage in early childhood (OR: IBD 5.3; CD 4.2; UC 4.8) were significantly associated with IBD, CD and UC. Having a fish or turtle aquarium (OR 6.0), major stressful life events (OR 5.6) and attending the same school concurrently with a sibling (OR 2.9) were significant risk factors for IBD. Duration of breastfeeding >6 months (OR: IBD 0.4; UC 0.2) and safe water consumption (OR: IBD 0.2; UC 0.2) reduced the odds of having IBD and UC, respectively. Being vaccinated for rotavirus reduced the odds of developing IBD (OR 0.1). CONCLUSIONS: Several risk and protective factors were identified in this environmental risk study in Southeast Asian children with IBD. This knowledge has important implications in understanding disease aetiology and future prevention strategies to reduce the development of IBD in Southeast Asian children.