2 Minute Medicine Rewind October 21, 2024
In Utero Exposure to Maternal COVID-19 and Offspring Neurodevelopment Through Age 24 Months
1. In utero exposure to maternal COVID-19 was not associated with increased risk for neurodevelopmental impairment in early childhood up to age 24 months.
Evidence Rating Level: 1 (Excellent)
Research on whether COVID-19 infection during pregnancy affects neurodevelopment of offspring has been mixed. Limitations in previous studies included small sample sizes and short follow-up periods (< 1 year). This large prospective cohort study thus investigated the association between in utero exposure to maternal COVID-19 and abnormal neurodevelopmental among offspring up to 24 months old. Data was collected from the ASPIRE (Assessing the Safety of Pregnancy in the Coronavirus Pandemic) trial. This nationwide prospective cohort included newly pregnant adults aged >18 years, recruited from all 50 US states and Puerto Rico between May 14, 2020, to August 23, 2021. Follow-ups were conducted at 12, 18, and 24 months postpartum. The Ages & Stages Questionnaires, Third Edition (ASQ-3) screening tool was used to determine the risk of neurodevelopment delay, indicated by an abnormal score that was defined as scoring below the predefined threshold on any of 5 developmental domains. In total, 2003 participants were included in this study (mean (SD) age, 33.3 (4.2) years), of which 217 (10.8%) experienced prenatal infection (exposed) (mean (SD) age, 33.5 (4.2) years). Neurodevelopmental outcomes were available for 1757 children 12 months of age, 1522 at 18 months, and 1523 at 24 months. The prevalence of abnormal screens for exposed vs. unexposed offspring was 64 of 198 (32.3%) vs. 458 of 1559 (29.4%) at 12 months of age, 36 of 161 (22.4%) vs. 279 of 1361 (20.5%) at 18 months of age, 29 of 151 (19.2%) vs. 230 of 1372 (16.8%) at 24 months of age. No differences were found in risk of abnormal neurodevelopmental screens between exposed and non-exposed groups observed at age 12 months (adjusted risk ratio (ARR), 1.07 [95% CI, 0.85-1.34]), age 18 months (ARR, 1.15 [95% CI, 0.84-1.57]), or age 24 months (ARR, 1.01[95% CI, 0.69-1.48]). Additionally, there was no association between SARS-CoV-2 infection and abnormal ASQ-3 scores among those at age 12 months (ARR, 1.10 [95% CI, 0.88-1.38]), age 18 months (ARR, 1.15 [95% CI, 0.84-1.57]), or age 24 months (ARR, 0.99 [95% CI, 0.67-1.46]). Furthermore, no differences in risk of neurodevelopment delay were observed based on trimester of infection, presence vs. absence of COVID-19 related fever, or breakthrough infection following vaccination vs. primary infection. Overall, study findings suggest that SARS-CoV-2 infection during pregnancy is not associated with abnormal neurodevelopmental scores in children up to 24 months of age. Longitudinal studies are needed to validate study findings.
Ambient Air Pollution Exposure and Outcomes in Patients Receiving Lung Transplant
1. Elevated PM2.5 air pollution exposure at the zip code of residence at the time of lung transplant was associated with increased hazard of death or graft failure.
Evidence Rating Level: 2 (Good)
Although lung transplant is intended to be a life-prolonging treatment for patients with irreversible end-stage lung diseases, life expectancy post-transplant is relatively modest, with a median survival of 5.5 to 6.5 years. Ambient particulate matter (PM) air pollution has been linked to adverse effects in various health domains, including respiratory health. PM2.5 air pollution refers to fine, inhalable particles with diameters < 2.5 μm. While it is evident that PM2.5 is associated with negative health outcomes, it is unclear how PM2.5 is associated with lung transplant outcomes. This study thus investigated the association between PM2.5 air pollution exposure and health outcomes in lung transplant recipients. This retrospective cohort study analyzed data from the multi-center US registry, United Network for Organ Sharing (UNOS), and included patients who received lung transplants between May 2005 and December 2016. The primary exposure was annual PM2.5 exposure obtained from the zip code of residence and year of transplant, based on previously published estimates of PM2.5 concentration across North America. The primary outcome was time to death or lung allograft failure after lung transplant. Among 18,265 lung transplant recipients, 1790 (9.8%) patients had resident zip code annual PM2.5 exposure equal to or greater than the Environmental Protection Agency (EPA) standard of 12μg/m3 (mean age (SD) = 54.7 ±12.7 years, male N (%) = 1038 (58%), mean BMI (SD) = 25.0 (4.6) kg/m2), and 16, 475 patients (90%) had resident zip code annual PM2.5 exposure less than the EPA standard (mean age (SD) = 55.4 (13.2) years, male N (%) = 9899 (60%), mean BMI (SD) = 25.1 (4.6) kg/m2). Median graft survival was 4.87 years (95% CI, 4.57-5.23) and 5.84 years (95% CI, 5.71- 5.96) for recipients living in high PM2.5 areas and low PM2.5 areas, respectively. Lung transplant recipients with residence in a zip code with annual PM2.5 exposure greater than or equal to the EPA standard was associated with an 8% increased hazard of death or graft failure (adjusted HR, 1.08; 95% CI, 1.01-1.15) compared to those with residence in a zip code with exposure less than the EPA standard. Additionally, each 1 μg/m3 increase in PM2.5 exposure was associated with a 1% increase in the hazard of death or graft failure (adjusted HR, 1.01; 95% CI, 1.00-1.02). Overall, study findings indicate that lung transplant recipients who resided in areas with higher levels of PM2.5 air pollution had a greater risk of worse survival post-transplant. Future research is necessary to explore mechanisms underlying study findings to and determine strategies for modifying risk at individual and population levels.
1. Increased levels of hypersensitive C-reactive protein was associated with increased risk of non-alcoholic fatty liver disease among non-obese individuals.
Evidence Rating Level: 3 (Average)
Non-alcoholic fatty liver disease (NAFLD) is the most common liver condition worldwide; yet, its pathogenesis remains unclear and there is no definitive treatment. Hypersensitive C-reactive protein (hs-CRP) is a marker of systemic inflammation and has been associated with NAFLD. As few studies have focused on non-obese populations, this study investigated whether hs-CRP was associated with NAFLD among non-obese individuals. Participants were recruited from a Health Examination Center in Ningbo City, China from March 2017 to November 2017. Participants were divided into NAFLD group and control group. Levels of hs-CRP were categorized into quartiles: quartile 1 (≤ 0.3 mg/L), quartile 2 (> 0.4 mg/L- ≤ 0.5 mg/L), quartile 3 (> 0.5 mg/L- ≤ 1.0 mg/L), and quartile 4 (> 1.1 mg/L). Among the 6558 participants included in the study, 1396 were in the NAFLD group (mean age ±SD = 51.5 ± 12.8 years, male N (%) = 1056 (76%), mean BMI = 23.7 ± 1.8 kg/m2) and 5162 were in the control group (mean age ±SD = 48.4 ±15.3 years, male N (%) = 3184 (62%), mean BMI = 21.5 ± 2.1 kg/m2). Compared to the control group, the NAFLD group had higher hs-CRP, age, waist circumference, BMI, and systolic and diastolic blood pressure, among others (p < 0.001). Prevalence of NAFLD was higher among individuals in the upper quartiles of hs-CRP levels (p < 0.001). Additionally, NAFLD risk increased with each higher quartile of hs-CRP (Odds Ratio (OR) 95%CI: quartile 2 = 1.79 (2.19, 2.69); quartile 3 = 3.50 (2.90, 4.21), quartile 4 = 5.39 (4.50, 6.47)). Results remained significant after adjusting for covariates (p < 0.05). Overall study findings suggest that hs-CRP levels may be an important risk factor for NAFLD in non-obese individuals. Future studies are needed to validate study results and explore the mechanisms underlying these findings.
1. Half of patients visiting the ER for acute migraine could have been diagnosed earlier.
Evidence Rating Level: 2 (Good)
Headache is a common primary complaint for patients visiting an emergency room (ER), accounting for about 1–4% of all ER visits and for 8–14% of consultations at neurological ERs globally. The majority (75%) of these patients suffer from primary headache disorders, mainly migraine. Some patients experiencing migraines may have already experienced multiple attacks prior to their ER visit but were not diagnosed. Given the high prevalence (36%) of migraine without an aura in Switzerland, this study aimed to quantify the problem of missed migraine diagnosis prior to ER visits. This prospective observational study was conducted at the University Hospital of Bern, Switzerland from March 2019 to November 2021. Adults > 18 years who visited the ER with the primary complaint of acute headache were included. Out of 301 patients recruited, 137 were diagnosed with acute migraine attacks, of which 108 (79%) had previous migraine attacks (mean ±SD age = 40.6 ± 15.9, 74% female). Out of these 108 patients, only 54 (50%) were previously diagnosed with migraine. Overall, this study found that although the majority of patients visiting the ER for acute migraine attacks had experienced previous migraine attacks, only half of these patients had been diagnosed. These findings suggest that migraine is underdiagnosed in prehospital care and that timely diagnosis with prescription of a specific acute treatment may prevent unnecessary ER visits.
Sex differences in mortality among patients with lupus nephritis
1. Males with lupus nephritis had higher all-cause mortality and proportion of infection-related death compared to females.
Evidence Rating Level: 2 (Good)
Lupus nephritis (LN) is a severe complication of systemic lupus erythematosus (SLE) that may result in end-stage renal disease (ESRD). Sex differences play a role in chronic kidney diseases and SLE with more females being affected (female-to-male ratio 9:1) but males exhibiting more severe kidney involvement. As research on sex differences in LN has focused on Western populations, knowledge gaps exist in the prognostic significance of sex in LN among other ethnic groups. As the prognostic importance of sex in LN remains controversial, this study thus investigated the prognostic importance of sex in LN in a Chinese population. This retrospective cohort study analyzed biopsy-confirmed LN patients, diagnosed between January 1, 1996, and December 31, 2018. The primary outcome was mortality, and the secondary outcomes included doubling of serum creatinine and end-stage renal disease (ESRD). Among the 1048 patients included in the study, 178 (17%) were male (mean age = 25 years (17-35)) and 870 (83%) were female (mean age = 28 years (21-37)). Male patients exhibited more aggressive features such as earlier disease onset, higher blood pressure, and elevated levels of many biomarkers of kidney dysfunction (p < 0.05). Despite comparable distribution of LN pathological classifications between sexes, male patients exhibited a greater number of renal lesions, including more total crescents, cellular crescent formations, higher levels of glomerular leukocyte infiltration, and Activity Index (AI) (p < 0.05). During a median follow-up period of 112 months, death was reported in 141 patients (15.3%). The mortality rate was higher among male patients (24.2% of all males) compared to females (13.5% of all females). No sex differences were observed for doubling of serum creatine and ESRD. Independent risk factors for survival in LN patients included being male (hazard ratio (HR) 95%CI = 1.79 (1.22–2.64)), older age of renal biopsy (HR 95% = 1.02 (CI 1.01–1.04)), and increased Chronicity Index (HR 95%CI = 1.18 (1.07–1.3)). Infections were the leading causes of mortality, with a higher proportion of infection-related deaths observed for male patients (55.3% for male, 35% for female, p = 0.007). Overall, males in the study cohort had higher all-cause mortality and proportion of infection-related death. Future research is needed to elucidate the sex disparities to optimize care for patients with LN.
Image: PD
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