Project description:IntroductionSevere acute respiratory syndrome coronavirus-2 (SARS-CoV-2) may trigger autoimmune disease (AD) through initial innate immune activation with subsequent aberrations in adaptive immune cells leading to AD. While there are multiple reports of incident AD diagnosed after COVID-19, the risk in the context of key circulating strains is unknown.MethodsTriNetX, a global, federated, health research network providing access to electronic medical records across 74 healthcare organizations, was utilized to define an adult cohort between January 1, 2020, and March 3, 2023. Exposure was defined as COVID-19 diagnosis (ICD-10 code or positive laboratory test). Age- and sex-propensity score-matched controls never had COVID-19 diagnosed. Outcomes were assessed 1 month to 1 year after the index date. Patients with AD prior to or within 1 month after the index date were excluded from the primary analysis. Incidence and risk ratios of each AD were assessed.ResultsA total of 3,908,592 patients were included. Of 24 AD patients assessed, adjusted risk ratios for eight AD patients who had COVID-19 were higher compared to those who had no COVID-19. Cutaneous vasculitis (adjusted hazard ratio (aHR): 1.82; 95% CI 1.55-2.13), polyarteritis nodosa (aHR: 1.76; 95% CI 1.15-2.70), and hypersensitivity angiitis (aHR: 1.64; 95% CI 1.12-2.38) had the highest risk ratios. Overall, psoriasis (0.15%), rheumatoid arthritis (0.14%), and type 1 diabetes (0.13%) had the highest incidence during the study period, and of these, psoriasis and diabetes were more likely after COVID-19. The risk of any AD was lower if COVID-19 was diagnosed when Omicron variants were the predominant circulating strains. A positive antinuclear antibody was more likely and predictive of AD after COVID-19.DiscussionSARS-CoV-2 may be a potential trigger for some AD, but the risk for AD may decrease with time given the apparent lower risk after infection with Omicron variants.
Project description:BackgroundThis study aimed to compare obstetric outcomes in Korean women with and without future cardiovascular disease (CVD) within 10 years after pregnancy, and assessed whether pregnancy complications are independent risk factors, and whether the combination of pregnancy complications has an additive function for risk factors for CVD.MethodsThis was a nationwide population-based study combining the database of the Korea National Health Insurance claims and National Health Screening Programs to assess preeclampsia, low birth weight (LBW), and preterm delivery as risk factors for CVD. Cox proportional hazards models was used to evaluate the risk of total CVD, ischemic heart disease (IHD), and stroke after the pregnancy complications, with adjustment for potential confounding variables.ResultsWomen with CVD were likely to have a higher prevalence of pregnancy complications than women without CVD. The risk of total CVD was associated with preeclampsia (adjusted hazard ratio (HR), 1.60 [95% confidence interval (CI) 1.50-1.72]), LBW (1.20 [1.12-1.28]), and preterm delivery (1.32 [1.22-1.42]), after adjustment for confounders, including cardiovascular risk factors before pregnancy. The risk estimates of pregnancy complications for IHD were higher than those for stroke. In this study, the risk of total CVD was higher in the combined presence of preeclampsia and preterm delivery (2.23 [1.57-3.17] or all three complications (2.06 [1.76-2.40]), relative to no complications. The highest HR was noted in the risk of all pregnancy complications for IHD (2.39 [1.98-2.89]).ConclusionPreeclampsia, preterm delivery, and LBW were independently associated with CVD in young Korean women. In addition, the combination of pregnancy complications had less-than-additive effects on CVD incidence.
Project description:ObjectiveAutoimmune conditions are associated with an increased risk of adverse pregnancy complications and outcomes, suggesting that pregnancy complications may mediate the excess risk. We performed a causal mediation analysis to quantify the mediated effects of autoimmune conditions on adverse pregnancy outcomes.MethodsWe queried a California birth cohort created from linked birth certificates and hospital discharge summaries. From 2,963,888 births, we identified women with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), psoriasis, and inflammatory bowel disease (IBD). Pregnancy complications included preeclampsia/hypertension, gestational diabetes mellitus, and infection in pregnancy. Adverse pregnancy outcomes were preterm birth, cesarean delivery, and small for gestational age. We performed a mediation analysis to estimate the total effects of each autoimmune condition and adverse pregnancy outcome and the indirect effects through pregnancy complications.ResultsAll 4 autoimmune conditions were associated with preterm birth and cesarean delivery, and RA, SLE, and IBD were associated with offspring that were small for gestational age. The strongest mediator of RA, SLE, and psoriasis was preeclampsia/hypertension, accounting for 20-33% of the excess risk of preterm births and 10-19% of excess cesarean deliveries. Gestational diabetes mellitus and infections generally mediated <10% of excess adverse pregnancy outcomes. Of the 4 autoimmune conditions, selected pregnancy complications mediated the least number of adverse pregnancy outcomes among women with IBD.ConclusionWe found evidence that some excess risk of adverse pregnancy outcomes is mediated through pregnancy complications, particularly preeclampsia/hypertension. Quantifying excess risk and associated pathways provides insight into the underlying etiologies of adverse pregnancy outcomes and can inform intervention strategies.
Project description:Rabbit production holds significant relevance in modern agriculture due to its potential as a sustainable source of high-quality protein and efficient feed conversion, contributing to food security and economic diversification. Nevertheless, studies incorporating feto-maternal monitoring in this species are uncommon. This review gathers research on the monitoring and evaluation of factors affecting rabbit gestation, providing a better understanding of the causes of prenatal development abnormalities. These include studies regarding how chronic maternal hypertension, gestational diabetes, maternal stress, ectopic gestation, maternal uterine ischemia and fetal hypoxia, intrauterine growth restriction, superfetation, maternal age, maternal nutritional status, maternal physical condition, maternal and embryonic genotype, and the intrauterine location of rabbit fetuses can potentially impact rabbits' reproduction and maternal and fetal health. Among other monitoring techniques, ultrasonography, considered one of the best tools for diagnosing pregnancy and conducting follow-up, is also reviewed. Details on measurable fetal-development parameters in rabbits and precautions to be considered before and during the examination are also provided. Additional studies are required to understand why some events occur and their consequences throughout gestation, allowing the determination of new biomarkers or cut-offs that can be helpful for early diagnosis and improve reproductive efficiency.
Project description:AimsTo explore the glucose-overload hypothesis of artefactual gestational diabetes (GDM) diagnosis in shorter women during oral glucose tolerance testing (OGTT), by investigating associations between height and maternal glycemia; and GDM and pregnancy complications in height-groups.MethodsWomen from GUSTO (n = 1100, 2009-2010) and NUH (n = 4068, 2017-2018) cohorts underwent a mid-gestation two and three time-point 75 g 2-hour OGTT, respectively. GDM-related complications (hypertensive disorders of pregnancy, preterm delivery, emergency cesarean section, neonatal intensive care unit admission, macrosomia, birthweight) were compared within shorter and taller groups, dichotomized by ethnic-specific median height.ResultsUsing WHO-1999 criteria, 18.8% (GUSTO) to 22.9% (NUH) of women were diagnosed with GDM-1999; and by WHO-2013 criteria, 21.9% (NUH) had GDM-2013. Each 5-cm height increment was inversely associated with GDM-1999 (adjusted odds ratio [aOR, 95% CI] = 0.81 [0.76-0.87], 2-h glycemia (adjusted β [aβ, 95% CI] = -0.171 mmol/L [-0.208, -0.135]) and 1-h glycemia (aβ = -0.160 mmol/L [-0.207, -0.112]). The inverse association between height and 2-h glycemia was most marked in "Other" ethnicities (Eurasians/Caucasians/mixed/other Asians) and Indians, followed by Chinese, then Malays. Compared with non-GDM, GDM-1999 was associated with preterm delivery (aOR = 1.76 [1.19-2.61]) and higher birthweight (aβ = 57.16 g [20.95, 93.38]) only among taller but not shorter women.ConclusionsOnly taller women had an increased odds of GDM-related pregnancy complications. An artefactual GDM diagnosis due to glucose-overload among shorter women is plausible.
Project description:Background: Having a pregnancy complicated by hypertensive disorders of pregnancy (HDP) and/or having a small or preterm baby put a woman at risk for later cardiovascular disease (CVD). It is uncertain if higher maternal CVD risk factors (reflected by increased peripartum CVD biomarker levels) account for this risk, or if experiencing a complicated pregnancy itself increases a woman's CVD risk (reflected by an increase in biomarker trajectories from early pregnancy to postpartum). Methods: We conducted a secondary analysis of an 8-week mindful eating and stress reduction intervention in 110 pregnant women. We used mixed linear regression analysis to compare CVD biomarker levels and trajectories, between women with and without a CVD-related pregnancy complication (including HDP [gestational hypertension or preeclampsia] or having a small for gestational age [<10th percentile] or preterm [<37 weeks] baby), at three times: (1) 12-20 weeks of gestation, (2) 3 months postpartum, and (3) 9 months postpartum. CVD biomarkers studied included serum glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), body mass index (BMI), blood pressure (BP), interleukin-6 (IL-6), tumor necrosis factor, and lipids. We adjusted for age, maternal smoking, prepregnancy BMI, BP, age × time, and BMI × time. Results: Women had a mean age of 28 years (standard deviation [SD] 6), mean prior pregnancies of 0.8 (SD 1.0), and 22 women had one or more CVD-related pregnancy complications. HOMA-IR, diastolic BP, triglyceride, high-density lipoprotein cholesterol, and IL-6 average levels, but not trajectories, differed among women with complicated versus normal pregnancy (all p values were ≤0.04). Peripartum glucose and systolic BP trajectories were statistically greater in complicated versus normal pregnancies (p values were 0.008 and 0.01, respectively). Conclusion: We conclude that the experience of a complicated pregnancy in addition to elevated CVD risk factor levels may both increase a woman's risk of future CVD. ClinicalTrials.gov Identifier: NCT01307683.
Project description:Sixty to seventy percent of IFN-γ(-/-) NOD.H-2h4 mice given sodium iodide (NaI)-supplemented water develop a slow onset autoimmune thyroid disease, characterized by thyrocyte epithelial cell (TEC) hyperplasia and proliferation (H/P). TEC H/P develops much earlier in CD28(-/-) mice and nearly 100% (both sexes) have severe TEC H/P at 4 mo of age. Without NaI supplementation, 50% of 5- to 6-mo-old CD28(-/-)IFN-γ(-/-) mice develop severe TEC H/P, and 2-3 wk of NaI is sufficient for optimal development of severe TEC H/P. Mice with severe TEC H/P are hypothyroid, and normalization of serum thyroxine levels does not reduce TEC H/P. Activated CD4(+) T cells are sufficient to transfer TEC H/P to SCID recipients. Thyroids of mice with TEC H/P have infiltrating T cells and expanded numbers of proliferating thyrocytes that highly express CD40. CD40 facilitates, but is not required for, development of severe TEC H/P, as CD40(-/-)IFN-γ(-/-)CD28(-/-) mice develop severe TEC H/P. Accelerated development of TEC H/P in IFN-γ(-/-)CD28(-/-) mice is a result of reduced regulatory T cell (Treg) numbers, as CD28(-/-) mice have significantly fewer Tregs, and transfer of CD28(+) Tregs inhibits TEC H/P. Essentially all female IFN-γ(-/-)CD28(-/-) NOD.H-2h4 mice have substantial lymphocytic infiltration of salivary glands and reduced salivary flow by 6 mo of age, thereby providing an excellent new model of autoimmune exocrinopathy of the salivary gland. This is one of very few models where autoimmune thyroid disease and hypothyroidism develop in most mice by 4 mo of age. This model will be useful for studying the effects of hypothyroidism on multiple organ systems.
Project description:ImportanceWomen are recommended to limit caffeine consumption to less than 200 mg per day based on risks to fetal health. Impacts of caffeine on maternal health remain unclear.ObjectiveTo determine whether caffeinated-beverage intake and plasma caffeine and paraxanthine are associated with cardiometabolic complications in pregnancy (ie, gestational diabetes [GDM], preeclampsia, and gestational hypertension [GH]).Design, setting, and participantsThis cohort study used data from a longitudinal pregnancy cohort study from the National Institute of Child Health and Human Development (NICHD) Fetal Growth Studies-Singletons (2009-2013). This post hoc secondary analysis of 2802 pregnant women without major chronic conditions enrolled at 12 US clinical sites was completed in 2021. The final sample for caffeinated beverage analyses included 2583 women. After excluding women who did not consent to have their biospecimens stored for future research (n = 54), plasma caffeine analyses included 2529 women. Analyses of caffeine consumption and fasting cardiometabolic profiles included 319 women.ExposuresDaily total caffeine intake was estimated at 10 to 13 gestational weeks and 16 to 22 gestational weeks based on self-reported past week intake of caffeinated coffee, tea, soda, and energy drinks. Plasma caffeine and paraxanthine were measured in specimens collected at 10 to 13 weeks.Main outcomes and measuresClinical diagnoses of GDM, preeclampsia, GH, glucose concentrations from GDM screening, and blood pressure were extracted from medical records.ResultsParticipants had a mean (SD) age of 28.1 (5.5) years and 422 participants (16.3%) were Asian/Pacific Islander women, 741 (28.9%) were Hispanic women, 717 (27.8%) were non-Hispanic Black women, and 703 (27.2%) were non-Hispanic White women. At 10 to 13 weeks, 1073 women (41.5%) reported consuming no caffeinated beverages, 1317 (51.0%) reported consuming 1 mg/d to 100 mg/d, 173 (6.7%) reported consuming 101 mg/d to 200 mg/d, and 20 (0.8%) reported consuming more than 200 mg/d. At 16 to 22 weeks, 599 women (23.6%) reported consuming no caffeinated beverages, 1734 (68.3%) reported consuming 1 mg/d to 100 mg/d, 186 (7.3%) reported consuming 101 mg/d to 200 mg/d, and 20 (0.8%) reported consuming more than 200 mg/d caffeinated beverages. Intake at 16 to 22 weeks was associated with lower GDM risk and lower glucose concentrations (1 mg/d to 100 mg/d vs none: relative risk, 0.53 [95% CI, 0.35 to 0.80]; β, -2.7 mg/dL [95% CI, -5.4 mg/dL to 0 mg/dL]) and lower C-reactive protein and C-peptide concentrations and favorable lipid profiles. Total plasma caffeine and paraxanthine at 10 to 13 weeks was inversely associated with glucose (quartile 4 vs quartile 1: β = -3.8 mg/dL [95% CI, -7.0 mg/dL to -0.5 mg/dL]; trend of P = .01). No associations were observed with preeclampsia or GH.Conclusions and relevanceIn this cohort study, second trimester caffeinated beverage intake within current recommendations was associated with lower GDM risk, but not preeclampsia or GH. These findings may be reassuring for women with moderate caffeine intake.
Project description:BACKGROUND:Spontaneous abortions, intrauterine growth restriction, and preeclampsia are thought to be caused by defective placentation and are associated with increased risk of adverse outcomes in subsequent pregnancies. However, it is not known whether the recurrence of adverse outcomes is associated with the recurrence of placental pathology. We hypothesized that recurrent maternal vascular malperfusion (MVM) underlies the recurrence of adverse outcomes. METHODS:Using data from the National Collaborative Perinatal Project, we assessed the recurrence of pregnancy complications and MVM lesions (N = 3865), associations between a history of spontaneous abortions and MVM lesions or adverse outcomes in subsequent pregnancies (N = 8312), and whether the recurrence of pregnancy complications occurred independently of the presence of MVM lesions. RESULTS:The odds of an MVM lesion were higher for a woman who had had an MVM lesion in a previous pregnancy (aOR = 1.6; 95% CI 1.3-1.9), although this was marginally non-significant after adjusting for covariates such as gestational age, race and BMI. The odds of preeclampsia, a small-for-gestational-age infant, premature delivery and early pregnancy loss were 2.7-5.0 times higher if there had been that same adverse outcome in a previous pregnancy. A history of spontaneous abortions was associated with higher risk of a small-for-gestational-age baby (aOR = 2.4; 95% CI 1.7-3.4) and prematurity (aOR = 5.1; 95% CI 2.3-11.5 for extremely preterm), but not preeclampsia. The recurrence of adverse outcomes was significant when restricting analyses to women without MVM lesions. Similarly, associations between adverse outcomes and previous spontaneous abortions were significant when statistically controlling for the presence of MVM lesions, or excluding pregnancies with MVM lesions. CONCLUSIONS:Women with adverse outcomes in one pregnancy are at higher risk of complications in subsequent pregnancies. However, there is significant recurrence of adverse outcomes even in the absence of MVM.
Project description:Autoimmune diseases (AID) predominantly affect women of reproductive age. While basic molecular studies have implicated persisting fetal cells in the mother in some AID, supportive epidemiological evidence is limited. We investigated the effect of vaginal delivery, caesarean section (CS) and induced abortion on the risk of subsequent maternal AID. Using the Danish Civil Registration System (CRS) we identified women who were born between 1960 and 1992. We performed data linkage between the CRS other Danish national registers to identify women who had a pregnancy and those who developed AID. Women were categorised into 4 groups; nulligravida (control group), women who had 1st child by vaginal delivery, whose 1st delivery was by CS and who had abortions. Log-linear Poisson regression with person-years was used for data analysis adjusting for several potential confounders. There were 1,035,639 women aged >14 years and 25,570 developed AID: 43.4% nulligravida, 44.3% had their first pregnancy delivered vaginally, 7.6% CS and 4.1% abortions. The risk of AID was significantly higher in the 1st year after vaginal delivery (RR = 1.1[1.0, 1.2]) and CS (RR = 1.3[1.1, 1.5]) but significantly lower in the 1st year following abortion (RR = 0.7[0.6, 0.9]). These results suggest an association between pregnancy and the risk of subsequent maternal AID. Increased risks of AID after CS may be explained by amplified fetal cell traffic at delivery, while decreased risks after abortion may be due to the transfer of more primitive fetal stem cells. The increased risk of AID in the first year after delivery may also be related to greater testing during pregnancy.