Risk Factors for Thyroid Dysfunction in Pregnancy: An Individual Participant Data Meta-Analysis.

Background: International guidelines recommend targeted screening to identify gestational thyroid dysfunction. However, currently used risk factors have questionable discriminative ability. We quantified the risk for thyroid function test abnormalities for a subset of risk factors currently used in international guidelines. Methods: We included prospective cohort studies with data on gestational maternal thyroid function and potential risk factors (maternal age, body mass index [BMI], parity, smoking status, pregnancy through in vitro fertilization, twin pregnancy, gestational age, maternal education, and thyroid peroxidase antibody [TPOAb] or thyroglobulin antibody [TgAb] positivity). Exclusion criteria were pre-existing thyroid disease and use of thyroid interfering medication. We analyzed individual participant data using mixed-effects regression models. Primary outcomes were overt and subclinical hypothyroidism and a treatment indication (defined as overt hypothyroidism, subclinical hypothyroidism with thyrotropin >10 mU/L, or subclinical hypothyroidism with TPOAb positivity). Results: The study population comprised 65,559 participants in 25 cohorts. The screening rate in cohorts using risk factors currently recommended (age >30 years, parity ≥2, BMI ≥40) was 58%, with a detection rate for overt and subclinical hypothyroidism of 59%. The absolute risk for overt or subclinical hypothyroidism varied <2% over the full range of age and BMI and for any parity. Receiver operating characteristic curves, fitted using maternal age, BMI, smoking status, parity, and gestational age at blood sampling as explanatory variables, yielded areas under the curve ranging from 0.58 to 0.63 for the primary outcomes. TPOAbs/TgAbs positivity was associated with overt hypothyroidism (approximate risk for antibody negativity 0.1%, isolated TgAb positivity 2.4%, isolated TPOAb positivity 3.8%, combined antibody positivity 7.0%; p < 0.001), subclinical hypothyroidism (risk for antibody negativity 2.2%, isolated TgAb positivity 8.1%, isolated TPOAb positivity 14.2%, combined antibody positivity 20.0%; p < 0.001) and a treatment indication (risk for antibody negativity 0.2%, isolated TgAb positivity 2.2%, isolated TPOAb positivity 3.0%, and combined antibody positivity 5.1%; p < 0.001). Twin pregnancy was associated with a higher risk of overt hyperthyroidism (5.6% vs. 0.7%; p < 0.001). Conclusions: The risk factors assessed in this study had poor predictive ability for detecting thyroid function test abnormalities, questioning their clinical usability for targeted screening. As expected, TPOAb positivity (used as a benchmark) was a relevant risk factor for (subclinical) hypothyroidism. These results provide insights into different risk factors for gestational thyroid dysfunction.

Global patterns of asthma burden related to environmental risk factors during 1990-2019: an age-period-cohort analysis for global burden of disease study 2019.

BACKGROUND: Change in asthma burden attributed to specific environmental risk factor has not been evaluated. OBJECTIVE: We aimed to explore the age, period, and cohort effects on asthma burden attributable to smoking and occupational asthmagens in different socio-demographic index (SDI) regions and the region and sex disparities. METHODS: Risk factor-specific asthma deaths and disability-adjusted life years (DALYs) rates were extracted from Global Burden of Disease study 2019, estimated by standard Combined Cause of Death Model and DisMod-MR 2.1 modeling tool. Age-period-cohort analysis was conducted to decompose age, period, and cohort effects on asthma burden. RESULTS: Smoking- and occupational asthmagens-related asthma deaths and DALYs rates dropped by > 45% during 1990-2019. In 2019, Africa, South and Southeast Asia had higher asthma burden than other regions. Male had higher asthma burden than female. Among nearly all age groups, low-middle SDI region had the highest smoking-related asthma burden, and low SDI region had the highest occupational asthmagens-related asthma burden. Inverse "V" shaped trend was observed in the above regions with increasing age. For smoking-related asthma deaths and DALYs rates, the most significant improvement of period rate ratio (RR) occurred in high SDI region, decreased from 1.67 (1.61, 1.74) to 0.34 (0.33, 0.36) and 1.61 (1.57, 1.66) to 0.59 (0.57, 0.61), respectively, as well as the cohort effect on smoking-related asthma burden. For occupational asthmagens-related asthma deaths and DALYs rates, the most sharply decrease of period and cohort RR appeared in the high and high-middle SDI regions. Low SDI region showed least progress in period and cohort RR of smoking- and occupational asthmagens-linked asthma burden. CONCLUSION: Smoking- and occupational asthmagens-related asthma burden sharply decreases, but region and sex disparities exist. Policy makers from low SDI region should reinforce tobacco control and prioritize workplace protection.

The relationship between cumulative ecological risk and health risk behaviors among Chinese adolescents.

OBJECTIVES: To explore the relationship between cumulative ecological risk and individual risky behavior and multiple forms of aggregated behaviors among adolescents, and examine the gender differences. METHODS: A large-scale, nationally representative, and students-based investigation was conducted in rural and urban areas of eight provinces in China from October to December 2021. A total of 22 868 adolescents with an average age of 14.64 years completely standardized questionnaire in which the sociodemographic characteristics, socio-ecological risk factors and risky behaviors were used to analyze. RESULTS: Of included students, 48.4% encountered the high level of social-ecological risk. The prevalence of breakfast intake not daily, alcohol use (AU), smoking, physical inactivity, prolonged screen time (ST) on weekdays and weekends, suicidal ideation, suicidal plan, suicidal attempt, and non-suicidal self-injury (NSSI) was 41.0%, 11.9%, 3.4%, 61.9%, 15.1%, 51.1%, 27.7%, 13.9%, 6.5% and 27.0% respectively. 22.2% of participants engaged in high-risk behaviors. All were significantly influences of increased cumulative ecological risk on individual behavior and low-risk clustering behaviors separately. The odds ratio of breakfast intake not daily, AU, smoking, physical inactivity, prolonged ST in weekday and weekend, suicidal ideation, suicidal plan, suicidal attempt, and NSSI for the adjusted model in low versus high level of cumulative ecological risk was respectively significant in both boy and girls, and the ratio of odds ratios (ROR) was separately 0.95 (p = 0.228), 0.67 (p < 0.001), 0.44 (p < 0.001), 0.60 (p < 0.001), 0.78 (p = 0.001), 0.83 (p = 0.001), 0.80 (p = 0.001), 0.83 (p = 0.022), 0.71 (p = 0.005), 0.75 (p = 0.001). Girls encountering a high level of cumulative ecological risk were more likely to engage in multiple forms of clustering risky behaviors than boys (RORs: 0.77, p = 0.001). CONCLUSIONS: Research and effective inventions at the social-ecological environment, based on the view of cumulative risk, are needed to promote the healthy development of behaviors in adolescence, and pay more attention to decreasing the occurrence of risky behaviours in girls than boys.

Placental inflammatory cytokines mRNA expression and preschool children's cognitive performance: a birth cohort study in China.

BACKGROUND: The immunologic milieu at the maternal-fetal interface has profound effects on propelling the development of the fetal brain. However, accessible epidemiological studies concerning the association between placental inflammatory cytokines and the intellectual development of offspring in humans are limited. Therefore, we explored the possible link between mRNA expression of inflammatory cytokines in placenta and preschoolers' cognitive performance. METHODS: Study subjects were obtained from the Ma'anshan birth cohort (MABC). Placental samples were collected after delivery, and real-time quantitative polymerase chain reaction (RT-qPCR) was utilized to measure the mRNA expression levels of IL-8, IL-1ß, IL-6, TNF-α, CRP, IFN-γ, IL-10, and IL-4. Children's intellectual development was assessed at preschool age by using the Wechsler Preschool and Primary Scale of Intelligence, Fourth Edition (WPPSI-IV). Multiple linear regression and restricted cubic spline models were used for statistical analysis. RESULTS: A total of 1665 pairs of mother and child were included in the analysis. After adjusting for confounders and after correction for multiple comparisons, we observed that mRNA expression of IL-8 (ß = - 0.53; 95% CI, - 0.92 to - 0.15), IL-6 (ß = - 0.58; 95% CI, - 0.97 to - 0.19), TNF-α (ß = - 0.37; 95% CI, - 0.71 to - 0.02), and IFN-γ (ß = - 0.31; 95% CI, - 0.61 to - 0.03) in the placenta was negatively associated with preschoolers' full scale intelligence quotient (FSIQ). Both higher IL-8 and IL-6 were associated with lower children's low fluid reasoning index (FRI), and higher IFN-γ was associated with lower children's working memory index (WMI). After further adjusting for confounders and children's age at cognitive testing, the integrated index of six pro-inflammatory cytokines (index 2) was found to be significantly and negatively correlated with both the FSIQ and each sub-dimension (verbal comprehension index (VCI), visual spatial index (VSI), FRI, WMI, processing speed index (PSI)). Sex-stratified analyses showed that the association of IL-8, IFN-γ, and index 2 with children's cognitive development was mainly concentrated in boys. CONCLUSIONS: Evidence of an association between low cognitive performance and high expression of placental inflammatory cytokines (IL-8, IL-6, TNF-α, and IFN-γ) was found, highlighting the potential importance of intrauterine placental immune status in dissecting offspring cognitive development.

[Combined effect of active smoking history and passive smoking during pregnancy on postpartum depression and anxiety].

OBJECTIVE: To explore the independent and combined effects of smoking and passive smoking during pregnancy on maternal depression, anxiety and depressive anxiety comorbidities. METHODS: From August 2020 to February 2022, women who underwent 42-day postpartum examination in Changfeng Women's Center and Shuangfeng Hospital of Hefei were recruited. Their depression and anxiety symptoms were assessed using EPDS Scale and GAD Scale, respectively, and smoking and passive smoking status during pregnancy were collected. Multivariate Logistic regression was used to analyze the independent and combined effects of smoking and passive smoking during pregnancy on postpartum depression, anxiety and depression and anxiety comorbidities. RESULTS: A total of 2 447 parturients were included, whose mean age was(29.23±4.20) years old.58.6% of parturients lived in urban areas.97.2% parturients had unassisted reproduction and 73.5% pregnancy intention was spontaneous. Among them, 362(14.8%) had depression, 523(21.4%) had anxiety, and 270(11.0%) had depression and anxiety comorbidities. In an independent analysis of effects, maternal smoking during pregnancy was statistically associated with postpartum depression(OR=3.86, 95%CI 2.37-6.28), anxiety(OR =2.58, 95%CI 1.60-4.17) and depressive anxiety comorbidity(OR = 3.34, 95%CI 2.00-5.71). Maternal passive smoking during pregnancy was also positively associated with the risk of postpartum depression(OR = 1.56, 95%CI 2.00-5.71), anxiety(OR=1.71, 95%CI 1.24-2.37) and depression and anxiety comorbidities(OR = 1.52, 95%CI 1.02-2.28), and the higher the frequency of exposure to passive smoking, the higher risk of depression, anxiety, and depressive and anxiety comorbidities. No interaction between smoking during pregnancy and passive smoking exposure on postpartum depression(RERI = 0.69, 95%CI-4.62-6.00; AP = 10.84, 95%CI-73.37-95.04; S= 0.58, 95%CI 0.02-15.18), anxiety(RERI=0.27, 95%CI 0.05-0.49; AP=4.02, 95%CI-0.52-8.57; S=0.78, 95%CI 0.64-0.94) and depression and anxiety comorbidities(RERI = 0.07, 95%CI-0.25-0.39; AP=1.74, 95%CI-6.03-9.52; S=0.93, 95%CI 0.68-1.27)was observed. CONCLUSION: Both smoking and passive smoking during pregnancy were positively associated with the risk of postpartum depression, anxiety and depressive anxiety comorbidity.

Moderating effects of smoking and drinking on the relationship between biological rhythm and psychological health and gender differences among adolescents.

OBJECTIVES: To determine whether smoking and drinking moderate the correlation between biological rhythm and mental health and the role of gender differences in these moderating effects. METHODS: Adolescents from three cities, all twelve middle schools (N = 7,986), named Shenzhen, Nanchang and Shenyang in China, were asked to complete a standardized questionnaire including the details of biological rhythm, psychological health, and the status of smoking and drinking. The PROCESS program was used to analyze whether smoking and drinking moderated the relationship between biological rhythm and psychological health. RESULTS: The analyses revealed poorer psychological health and greater likelihood of smoking and drinking in participants with higher scores for biological rhythm disorder (P < 0.001). Specifically, smoking and drinking accelerated the relationship between biological rhythm and psychological health in the total sample (B = 0.05, P < 0.05; B = 0.06, P < 0.001) and only the subgroup of girls (B = 0.09, P < 0.05; B = 0.12, P < 0.001), respectively. CONCLUSIONS: As the findings suggest, attention should be given to smoking, drinking and gender-specific approaches employed to alleviate the psychological disorders of adolescents with biological rhythm disorders.

Association of maternal thyroid peroxidase antibody during pregnancy with placental morphology and inflammatory and oxidative stress responses.

Background: Studies suggest that thyroid peroxidase antibody (TPOAb) positivity exposure during pregnancy may contribute to changes in placental morphology and pathophysiology. However, little is known about the association of maternal TPOAb during pregnancy with placental morphology and cytokines. This study focuses on the effect of repeated measurements of maternal TPOAb during pregnancy on the placental morphology and cytokines. Methods: Based on Ma'anshan Birth Cohort (MABC) in China, maternal TPOAb levels were retrospectively detected in the first, second and third trimesters. Placental tissues were collected 30 minutes after childbirth, placental morphological indicators were obtained by immediate measurement and formula calculation, and cytokine mRNA expression was detected by real-time quantitative polymerase chain reaction (RT-qPCR) afterward. Generalized linear models and linear mixed models were analyzed for the relationships of maternal TPOAb in the first, second and third trimesters with placental indicators. Results: Totally 2274 maternal-fetal pairs were included in the analysis of maternal TPOAb levels and placental morphology, and 2122 pairs were included in that of maternal TPOAb levels and placental cytokines. Maternal TPOAb levels in early pregnancy were negatively associated with placental length, thickness, volume, weight and disc eccentricity, while positively correlated with placental IL-6, TNF-α, CRP, CD68, MCP-1, IL-10, HO-1, HIF-1α and GRP78. In mid-pregnancy, maternal TPOAb levels were negatively correlated with placental length, width and area. In late pregnancy, maternal TPOAb levels were negatively correlated with placental length, area, volume and weight. Repeated measures analysis showed that maternal TPOAb positivity tended to increase placental TNF-α, CD68 and MCP-1 while decreasing placental length, width and area than TPOAb negativity. Repeated measures analysis showed that maternal TPOAb levels were positively correlated with placental IL-6, TNF-α, CD68, MCP-1, IL-10, HO-1, HIF-1α and GRP78, while negatively correlated with placental length, area, volume, weight, and disc eccentricity. Conclusion: There may be trimester-specific associations between maternal TPOAb levels and placental morphology and inflammatory and oxidative stress responses. The effect of maternal TPOAb levels on placental morphology is present throughout pregnancy. Early pregnancy may be the critical period for the association between maternal TPOAb levels and placental inflammatory and oxidative stress responses.

Waist-to-Height Ratio Is a Stronger Mediator in the Association between DASH Diet and Hypertension: Potential Micro/Macro Nutrients Intake Pathways.

Several studies have demonstrated that adhering to the Dietary Approaches to Stop Hypertension (DASH) diet may result in decreased blood pressure levels and hypertension risk. This may be an effect of a reduction in central obesity. In the current study, we explored the mediation role of multiple anthropometric measurements in association with DASH score and hypertension risk, and we investigated potential common micro/macro nutrients that react with the obesity-reduction mechanism. Our study used data from the National Health and Nutrition Examination Survey (NHANES). Important demographic variables, such as gender, race, age, marital status, education attainment, poverty income ratio, and lifestyle habits such as smoking, alcohol drinking, and physical activity were collected. Various anthropometric measurements, including weight, waist circumference, body mass index (BMI), and waist-to-height ratio (WHtR) were also obtained from the official website. The nutrient intake of 8224 adults was quantified through a combination of interviews and laboratory tests. We conducted stepwise regression to filter the most important anthropometric measurements and performed a multiple mediation analysis to test whether the selected anthropometric measurements had mediation effects on the total effect of the DASH diet on hypertension. Random forest models were conducted to identify nutrient subsets associated with the DASH score and anthropometric measurements. Finally, associations between common nutrients and DASH score, anthropometric measurements, and risk of hypertension were respectively evaluated by a logistic regression model adjusting for possible confounders. Our study revealed that BMI and WHtR acted as full mediators between DASH score and high blood pressure levels. Together, they accounted for more than 45% of the variation in hypertension. Interestingly, WHtR was found to be the strongest mediator, explaining approximate 80% of the mediating effect. Furthermore, we identified a group of three commonly consumed nutrients (sodium, potassium, and octadecatrienoic acid) that had opposing effects on DASH score and anthropometric measurements. These nutrients were also found to be associated with hypertension in the same way as BMI and WHtR in univariate regression models. The most important among these nutrients was sodium, which was negatively correlated with the DASH score (ß = -0.53, 95% CI = -0.56~-0.50, p < 0.001) and had a positive association with BMI (ß = 0.04, 95% CI = 0.01~0.07, p = 0.02), WHtR (ß = 0.06, 95% CI = 0.03~0.09, p < 0.001), and hypertension (OR = 1.09, 95% CI = 1.01~1.19, p = 0.037). Our investigation revealed that the WHtR exerts a greater mediating effect than BMI on the correlation between the DASH diet and hypertension. Notably, we identified a plausible nutrient intake pathway involving sodium, potassium, and octadecatrienoic acid. Our findings suggested that lifestyle modifications that emphasize the reduction of central obesity and the attainment of a well-balanced micro/macro nutrient profile, such as the DASH diet, could potentially be efficacious in managing hypertension.

Association Between Comorbid Anxiety and Depression and Health Risk Behaviors Among Chinese Adolescents: Cross-Sectional Questionnaire Study.

BACKGROUND: Comorbidity of psychiatric disorders such as depression and anxiety is very common among children and adolescents. Few studies have examined how comorbid anxiety and depression are associated with health risk behaviors (HRBs) in adolescents, which could inform preventative approaches for mental health. OBJECTIVE: We evaluated the association between HRBs and comorbid anxiety and depression in a large adolescent cohort. METHODS: We used data from 22,868 adolescents in the National Youth Cohort (China). Anxiety and depression symptoms were assessed using the 9-item Patient Health Questionnaire scale and the 7-item Generalized Anxiety Disorder scale, respectively. Comorbidity was determined by the coexistence of anxiety and depression. HRBs including poor diet, smoking, physical inactivity, and poor sleep, as well as the above HRB scores, were added to obtain the total HRB score (HRB risk index). Based on single and total HRB scores, we divided participants into low-, medium-, and high-risk groups. Potential confounders included gender, presence of siblings, regional economic level, educational status, self-rated health, parental education level, self-reported family income, number of friends, learning burden, and family history of psychosis. Correlation analysis was used to explore associations between single risk behaviors. Binary logistic regression estimated the association between HRBs and anxiety-depression comorbidity before and after adjusting for potential confounders. RESULTS: The comorbidity rate of anxiety and depression among Chinese adolescents was 31.6% (7236/22,868). There was a statistically significant association between each HRB (P<.05), and HRBs were positively associated with comorbid anxiety and depression in the above population. For single HRBs, adolescents with poor diet, smoking, and poor sleep (medium-risk) were more prone to anxiety-depression comorbidity after adjusting for confounders compared to low-risk adolescents. However, adolescents with all high-risk HRBs were more likely to have comorbid anxiety and depression after adjusting for confounders (poor diet odds ratio [OR] 1.50, 95% CI 1.39-1.62; smoking OR 2.17, 95% CI 1.67-2.81; physical inactivity OR 1.16, 95% CI 1.06-1.28; poor sleep OR 1.84, 95% CI 1.70-2.01). Moreover, in both unadjusted (medium risk OR 1.79, 95% CI 1.56-2.05; high risk OR 3.09, 95% CI 2.72-3.52) and adjusted (medium risk OR 1.57, 95% CI 1.37-1.80; high risk OR 2.33, 95% CI 2.03-2.68) models, HRB risk index, like clustered HRBs, was positively associated with anxiety-depression comorbidity, and the strength of the association was stronger than for any single HRB. In addition, we found that compared to girls, the association between clustered HRBs and anxiety-depression comorbidity was stronger in boys after adjustment. CONCLUSIONS: We provide evidence that HRBs are related to comorbid anxiety and depression. Interventions that decrease HRBs may support mental health development in adolescence, with the potential to improve health and well-being through to adulthood.

Trimester-specific effects of maternal exposure to single and mixed metals on cord serum inflammatory cytokines levels: A prospective birth cohort study.

BACKGROUND: Cord blood inflammatory cytokines are vital in early-life programming. An increasing number of studies concern the effect of maternal exposure to different metal elements during pregnancy on inflammatory cytokines, but limited studies have explored the association between maternal exposure to mixed metals and cord blood inflammatory cytokine levels. METHODS: We measured serum concentrations of vanadium (V), copper (Cu), arsenic (As), cadmium (Cd), and barium (Ba) in the first, second, and third trimesters and eight cord serum inflammatory cytokines (IFN-γ, IL-1ß, IL-6, IL-8, IL-10, IL-12p70, IL-17A, and TNF-α) in 1436 mother-child dyads from the Ma'anshan Birth Cohort. Generalized linear models and Bayesian kernel machine regression (BKMR) were performed to assess the association of single and mixed metal exposure during each trimester with cord serum inflammatory cytokine levels, respectively. RESULTS: Regarding metal exposure in the first trimester, V was positively associated with TNF-α (ß = 0.33, 95 % CI: 0.13, 0.53); Cu was positively associated with IL-8 (ß = 0.23, 95 % CI: 0.07, 0.39); Ba was positively associated with IFN-γ and IL-6; As was negatively associated with IFN-γ and IL-17A; and Cd was negatively associated with IFN-γ, IL-1ß, IL-12p70, IL-17A, and TNF-α. BKMR revealed that exposure to metal mixtures in the first trimester was positively associated with IL-8 and TNF-α but negatively associated with IL-17A. Moreover, V contributed the most to these associations. Interaction effects were observed between Cd and As and between Cd and Cu with IL-8, and between Cd and V with IL-17A. Among males, As decreased inflammatory cytokines; among females, Cu increased inflammatory cytokine levels, whereas Cd decreased inflammatory cytokine concentrations. CONCLUSIONS: Maternal exposure to metal mixtures in the first trimester interfered with cord serum inflammatory cytokine levels. The associations of maternal exposure to As, Cu and Cd with inflammatory cytokines showed sex differences. Further studies are warranted to support the findings and explore the mechanism of the susceptibility window and sex-specific disparity.

Polymorphisms of mtDNA in the D-loop region moderate the associations of BMI with HOMA-IR and HOMA-ß among women with polycystic ovary syndrome: a cross-sectional study.

PURPOSE: Polycystic ovary syndrome (PCOS) is one of the leading causes of infertility in women of childbearing age, and many patients with PCOS have obesity and insulin resistance (IR). Although obesity is related to an increased risk of IR, in clinical practice, PCOS patients exhibit different effects on improving insulin sensitivity after weight loss. Therefore, in the present study, we aimed to examine the moderating effect of polymorphisms of mtDNA in the D-loop region on the associations of body mass index (BMI) with the homeostasis model assessment of insulin resistance index (HOMA-IR) and pancreatic ß cell function index (HOMA-ß) among women with PCOS. METHODS: Based on a cross-sectional study, women with PCOS were recruited from the Reproductive Center of the First Affiliated Hospital of Anhui Medical University from 2015 to 2018. A total of 520 women who were diagnosed with PCOS based on the revised 2003 Rotterdam criteria were included in the study. Peripheral blood was collected from these patients, followed by DNA extraction, PCR amplification, and sequencing at baseline. HOMA-IR and HOMA-ß were calculated according to blood glucose-related indices. Moderating effect models were performed with BMI as an independent variable, polymorphisms of mtDNA in the D-loop region as moderators, and ln (HOMA-IR) and ln (HOMA-ß) as dependent variables. To verify the stability of moderating effect, sensitivity analysis was performed with the quantitative insulin sensitivity check index (QUICKI), fasting plasma glucose/fasting insulin (G/I), and fasting insulin as dependent variables. RESULTS: BMI was positively associated with ln (HOMA-IR) and ln (HOMA-ß) (ß = 0.090, p < 0.001; ß = 0.059, p < 0.001, respectively), and the relationship between BMI and ln (HOMA-IR) or ln (HOMA-ß) was moderated by the polymorphisms of mtDNA in the D-loop region. Compared with the respective wild-type, the variant -type of m.16217 T > C enhanced the association between BMI and HOMA-IR, while the variant-type of m.16316 A > G weakened the association. On the other hand, the variant-type of m.16316 A > G and m.16203 A > G weakened the association between BMI and HOMA-ß, respectively. The results of QUICKI and fasting insulin as dependent variables were generally consistent with HOMA-IR, and the results of G/I as dependent variables were generally consistent with HOMA-ß. CONCLUSION: Polymorphisms of mtDNA in the D-loop region moderate the associations of BMI with HOMA-IR and HOMA-ß among women with PCOS.

Prenatal Exposure to Air Pollution and Pre-Labor Rupture of Membranes in a Prospective Cohort Study: The Role of Maternal Hemoglobin and Iron Supplementation.

BACKGROUND: Exposure to air pollution in prenatal period is associated with prelabor rupture of membranes (PROM). However, the sensitive exposure time windows and the possible biological mechanisms underlying this association remain unclear. OBJECTIVE: We aimed to identify the sensitive time windows of exposure to air pollution for PROM risk. Further, we examined whether maternal hemoglobin levels mediate the association between exposure to air pollution and PROM, as well as investigated the potential effect of iron supplementation on this association. METHOD: From 2015 to 2021, 6,824 mother-newborn pairs were enrolled in the study from three hospitals in Hefei, China. We obtained air pollutant data [particulate matter (PM) with aerodynamic diameter ≤2.5µm (PM2.5), PM with aerodynamic diameter ≤10µm (PM10), sulfur dioxide (SO2), and carbon monoxide (CO)] from the Hefei City Ecology and Environment Bureau. Information on maternal hemoglobin levels, gestational anemia, iron supplementation, and PROM was obtained from medical records. Logistic regression models with distributed lags were used to identify the sensitive time window for the effect of prenatal exposure to air pollutant on PROM. Mediation analysis estimated the mediated effect of maternal hemoglobin in the third trimester, linking prenatal air pollution with PROM. Stratified analysis was used to investigate the potential effect of iron supplementation on PROM risk. RESULTS: We found significant association between prenatal exposure to air pollution and increased PROM risk after adjusting for confounders, and the critical exposure windows of PM2.5, PM10, SO2 and CO were the 21th to 24th weeks of pregnancy. Every 10-µg/m3 increase in PM2.5 and PM10, 5-µg/m3 increase in SO2, and 0.1-mg/m3 increase in CO was associated with low maternal hemoglobin levels [-0.94g/L (95% confidence interval (CI): -1.15, -0.73), -1.31g/L (95% CI: -1.55, -1.07), -2.96g/L (95% CI: -3.32, -2.61), and -1.11g/L (95% CI: -1.31, -0.92), respectively] in the third trimester. The proportion of the association between air pollution and PROM risk mediated by hemoglobin levels was 20.61% [average mediation effect (95% CI): 0.02 (0.01, 0.05); average direct effect (95%): 0.08 (0.02, 0.14)]. The PROM risk associated with exposure to low-medium air pollution could be attenuated by maternal iron supplementation in women with gestational anemia. CONCLUSIONS: Prenatal exposure to air pollution, especially in the 21st to 24th weeks of pregnancy, is associated with PROM risk, which is partly mediated by maternal hemoglobin levels. Iron supplementation in anemia pregnancies may have protective effects against PROM risk associated with exposure to low-medium air pollution. https://doi.org/10.1289/EHP11134.

Insomnia trajectories predict chronic inflammation over 2 years at the transition to adulthood.

Insomnia in adolescents is an important public health concern, as its impacts on both their current and future physical and mental health has been discussed. However, few longitudinal studies have examined insomnia and chronic inflammation at the transition from adolescence to adulthood. This study aimed to examine the predictive effects of insomnia and insomnia trajectories on inflammation in college students by using a prospective design. Using data from the College Student Behaviour and Health Cohort Study, which was conducted between April 2019 and April 2021, with an interval of 6 months. We investigated the associations between insomnia trajectories from Year 1 to Year 3 and five inflammatory biomarkers (C-reactive protein [CRP], tumour necrosis factor [TNF]-α, interleukin [IL]-6, IL-1ß, IL-10) at Year 3. The association of insomnia symptoms at baseline, Wave 1 or Wave 2 with inflammatory biomarkers at Wave 4 were also assessed. A total of 312 college students (males: 51.6%) aged 16-26 years (mean [SD] 18.82 [1.22] years) were analysed. We identified two insomnia trajectory classes: increasing insomnia (n = 63 [20.2%]) and decreasing insomnia (n = 249 [79.8%]). Generalised linear model analysis revealed that insomnia symptoms at Wave 1 were associated with significantly elevated CRP and TNF-α levels at Wave 4. Increasing insomnia trajectories predicted consistently higher levels of CRP, TNF-α and IL-10. However, after adjusting for potential confounders, these associations were significantly attenuated. Overall, the findings suggest that insomnia symptoms affect chronic inflammation at the transition to adulthood. Our study needs to be replicated in larger cohorts to further explore how inflammation interacts with insomnia to increase the susceptibility to adverse health conditions.

Serum Cu, Zn and IL-1ß Levels May Predict Fetal Miscarriage Risk After IVF Cycles: A Nested Case-Control Study.

To explore the association between serum-related indicators (levels of inflammatory cytokines and essential trace elements) and miscarriage risk among infertile women undergoing assisted reproductive techniques (ART) on the 14th day after embryo transfer, and to develop and establish a multivariable algorithm model that might predict pregnancy outcome. According to a nested case-control study design, a total of 100 miscarriage cases and 100 live birth controls were included in this study, and women in both groups were infertile and have underwent in vitro fertilization (IVF). Pregnancy tests were performed and serum levels of five essential trace elements (vanadium (V), copper (Cu), zinc (Zn), selenium (Se) and molybdenum (Mo)) and five inflammatory cytokines (interleukin-1ß (IL-1ß), IL-6, IL-8, IL-10 and tumor necrosis factor-α (TNF-α)) of the participants were measured on the 14th day after embryo transfer. The serum levels of five inflammatory cytokines were determined by multiple magnetic bead enzyme immunity analyzer; and the serum concentrations of five elements were determined simultaneously by inductively coupled plasma‒mass spectrometry (ICP ‒ MS). The logistic regression was used to evaluate the relationship between these serum indices and miscarriage risk among women undergoing ART, and a predictive model of pregnancy outcome based on these indices was established. The levels of IL-10, IL-1ß and TNF-α of infertile women in the live birth group were significantly higher than those in the miscarriage group (p = 0.009, p < 0.001, p = 0.006), and the levels of V, Cu, Zn and Se of infertile women in the live birth group were also significantly higher than those in the miscarriage group (all p < 0.001). Through logistic regression analyses, we found that serum levels of IL-1ß, TNF-α, V, Cu, Zn and Se were significantly and negatively associated with miscarriage risk. Different combination prediction models were generated according to the results of logistic regression analyses, and the combination of IL-1ß, Cu and Zn had the best prediction performance. The area under the curve (AUC) was 0.776, the sensitivity of the model was 60% and the specificity was 84%. In conclusion, the serum-related indicators of women undergoing ART on the 14th day after embryo transfer, including the inflammatory cytokines such as IL-1ß and TNF-α and the essential trace metal elements such as V, Cu, Zn and Se, were negatively correlated with miscarriage risk. A multivariate algorithm model to predict pregnancy outcome among women undergoing ART was established, which showed that IL-1ß, Cu and Zn might synergistically predict pregnancy outcome.

Gender- and age-specific associations of childhood maltreatment with peripheral serum inflammatory cytokines in middle school students.

Background: The impact of childhood maltreatment on multiple inflammatory cytokines among middle school students remains to be elucidated. This study aimed to examine the associations of different types of childhood maltreatment with peripheral serum inflammatory cytokines (interleukin-10, interleukin-1ß, interleukin-6, interleukin-8, and tumor necrosis factor-α) in middle school students, and to explore the differences in these associations between boys and girls and between late (≥15 and<20 years) and early (≥11 and <15 years) adolescence. Methods: A total of 1122 students were recruited from a boarding middle school. Each participant was asked to respond to a detailed questionnaire on childhood maltreatment, from whom one blood sample was drawn via venous blood. Results: In the overall sample there was no association between childhood maltreatment and peripheral serum inflammatory cytokines; (2) emotional abuse was significantly correlated with IL-1ß only in girls (B = -0.16; 95% CI, -0.28~-0.03; p = 0.06); (3) in late adolescence, emotional abuse, emotional neglect, and childhood maltreatment had marked link with IL-8 (B = 0.39; 95%CI, 0.16~0.63; p = 0.01; B =0.20; 95% CI, 0.04~0.37; p = 0.08; B = 0.50; 95% CI, 0.18~0.82; p = 0.01, respectively). Conclusion: These findings also strengthened an inference regarding the effects of childhood maltreatment on inflammation of students in late adolescence.

The effect of phthalates exposure during pregnancy on asthma in infants aged 0 to 36 months: a birth cohort study.

This cohort study sought to investigate the effects of phthalates exposure during pregnancy on offspring asthma and its association with placental stress and inflammatory factor mRNA expression levels. A total of 3474 pregnant women from the China Ma'anshan birth cohort participated in this study. Seven phthalate metabolites were detected in urine samples during pregnancy by solid phase extraction-high-performance liquid chromatography tandem mass spectrometry. Placenta stress and inflammation mRNA expression were assessed by real-time quantitative polymerase chain reaction (RT-qPCR). Early pregnancy may be the critical period when phthalates exposure increases the risk of asthma in infants and young children, and there is a certain gender difference in the risk of asthma in infants and young children. Moreover, through the placenta stress and inflammatory factor associated with infant asthma found anti-inflammatory factor of interleukin-10 (IL-10) mRNA expression will reduce the risk of 36-month-old male infant asthma. The expression of interleukin-4(IL-4) and macrophage (M2) biomarker cluster of differentiation 206(CD206) mRNA reduced the risk of asthma in 18-month-old female infants. Placental stress and inflammatory response were analyzed using mediating effects. Tumor necrosis factor-α (TNFα) showed a complete mediating effect between mono-benzyl phthalate (MBzP) exposure in early pregnancy and asthma in 12-month-old males, and IL-10 also showed a complete mediating effect between mono-n-butyl phthalate (MBP) exposure in early and late pregnancy and asthma in 36-month-old males. In summary, exposure to phthalates during pregnancy may contribute to the development of asthma in infants, which may be associated with placental stress and inflammation.

Selenium attenuates the association of co-exposure to arsenic, cadmium, and lead with cognitive function among Chinese community-dwelling older adults.

The effects of interactions between the toxic and essential metal mixtures on cognitive function are poorly understood. This study aims to identify the joint association of arsenic (As), cadmium (Cd), and lead (Pb) with cognitive function in older adults and the moderating role of selenium (Se), zinc (Zn), and copper (Cu) in this association. This study included 1000 community-dwelling older adults. Cognitive function was assessed by the Mini-Mental State Examination (MMSE). Blood concentrations of As, Cd, Pb, Se, Zn, and Cu were measured using inductively coupled plasma mass spectrometry. Linear regression and Bayesian kernel machine regression (BKMR) models were applied to assess the individual and joint associations of As, Cd, and Pb with cognitive function and to examine whether Se, Zn, and Cu (individually and as a mixture) modified these associations. In the adjusted single-metal models, both Cd (ß = - 0.37, 95% CI: - 0.73 to - 0.01) and Pb (ß = - 0.44, 95% CI: - 0.86 to - 0.02) were associated with MMSE scores, while Se (ß = 0.71, 95% CI: 0.30 to 1.13) exhibited a positive relationship with MMSE scores. Univariate exposure-response functions from BKMR models showed similar results. Moreover, the toxic metal mixture (As, Cd, and Pb) exhibited a significant negative association with MMSE scores in a dose-response pattern, with Pb being the greatest contributor within the mixture. The negative association of Pb alone or the toxic metal mixture with MMSE scores became weaker at higher concentrations of Se within its normal range, especially when Se levels were greater than the median (89.18 µg/L). Our findings support that Se can attenuate the negative associations of exposure to single Pb or the As, Cd, and Pb mixtures with cognitive function. Future prospective studies are needed to replicate our findings.

Exposure to multiple toxic metals and polycystic ovary syndrome risk: Endocrine disrupting effect from As, Pb and Ba.

BACKGROUND: Polycystic ovarian syndrome (PCOS) affects 5 % ~ 20 % of women of reproductive age and is a serious health problem. Whether exposure to lead (Pb), mercury (Hg), arsenic (As), barium (Ba) or (cadmium) Cd is associated with an increased risk of PCOS, particularly their joint effect as well as their association with the clinical phenotype of PCOS is limited and unclear. OBJECTIVES: We aimed to explore the associations of the blood Pb, Hg, As, Ba and Cd levels and risk of PCOS in Chinese women of reproductive age. METHODS: A case-control study was used and included 369 women with PCOS and 441 controls. The levels of Pb, Hg, As, Ba and Cd were measured in fasting blood samples collected on the 2nd or 3rd day of menstruation or vaginal bleeding after drug withdrawal; basal sex hormone levels, fasting glucose and fasting insulin were measured simultaneously. Unconditional logistic regression models were used to assess the relationship of the blood Pb, Hg, As, Ba or Cd levels with PCOS risk. Bayesian kernel machine regression (BKMR) was used to assess the joint effect of Pb, Hg, As, Ba and Cd on PCOS risk and estimate which metal or metals contributed most to the association. Multiple linear regression models were used to investigate the relationships between the levels of selected metals and parameters of the clinical PCOS phenotype. RESULTS: The mean ± SD ages of women in the case and control groups were 28.80 ± 3.39 and 28.97 ± 2.39 years, respectively; their mean ± SD BMIs were 23.86 ± 3.51 kg/m2 and 22.08 ± 3.14 kg/m2, respectively. The blood levels of three metals (Pb, As and Ba) were statistically associated with PCOS risk based on single-metal models. With each natural logarithm transformed (ln) unit increase in blood concentrations of Pb, higher likelihood of PCOS can be found, the adjusted odd ratio (aOR) and 95 % confidence interval (CI) was 1.83 (1.35-2.48), and these for As and Ba were 2.49 (1.86-3.33) and 1.20 (1.04-1.39), respectively. Compared with women at the first tertile group, higher likelihoods of PCOS among women in the second and third tertiles of the Pb group were observed, aORs and 95 % CIs were 1.81 (1.22-2.68) and 2.08 (1.42-3.04), respectively; and higher likelihoods of PCOS among women in the third tertiles of As and Ba group were also observed, the aORs and 95%CIs were 2.83 (1.93-4.15) and 1.89 (1.32-2.72), respectively. BKMR analysis also showed a statistically significant and positive joint effect of five metals on PCOS risk when the blood levels of five metals were all above the 55th percentile compared with their median levels, and As (100 %) and Pb (67.44 %) were the major contributors to the association. The blood As levels were positively associated with the luteinizing hormone (LH) levels and LH/FSH (follicle-stimulating hormone) ratio values, the blood Ba levels were negatively associated with the FSH levels, and the blood Pb levels were positively associated with the fasting insulin levels and homeostasis model assessment of insulin resistance (HOMA-IR) values. CONCLUSIONS: Our results suggest a positive association between exposure to multiple toxic metals (Pb, Hg, As, Ba and Cd) and PCOS risk. As and Pb were the major contributors, evaluated either as a single agent or metal mixture; and Pb, As, and Ba were associated with different parameters of the clinical PCOS phenotype. Additional studies are warranted to confirm these associations, particularly regarding the synergistic effect of toxic metals.