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•Most pregnant women were exposed to preferred veterinary antibiotic at low levels.•Multiple measurements were made to characterize antibiotic exposure during pregnancy.•A total of ...4.5% urine samples were observed having hazard index values exceeding 1.•Urinary antibiotic levels characteristically varied by sampling seasons.
Multiple antibiotics are widely used in clinic practice and livestock husbandry, but exposure data based on repeated measurements are scarce among pregnant women. Here, we biomonitored 41 antibiotics and their two metabolites in urine samples from 3235 pregnant women over three trimesters. Spearman’s correlation coefficient, intraclass correlation coefficient (ICC), percentile analysis and linear mixed models were employed to evaluate the correlations, variability, co-exposure patterns and predictors of antibiotics, respectively. Pregnant urinary creatinine-adjusted concentrations of antibiotics were used to estimate daily exposure dose and assessed health risks. The target antibiotics were detected in more than 90% of urine samples, primarily as preferred as veterinary antibiotics (PVAs), and the 95th percentile urinary concentrations of each individual antibiotics were range from below the limits of detection to 5.74 ng/mL. We observed considerable within-subject variation (ICC: 0.05–0.63) of urinary antibiotics concentrations during pregnancy. More than half pregnant women were co-exposed to two or more antibiotics of different usage classes, while both co-exposure to high percentiles of three usage antibiotics at one trimester or exposure to single usage antibiotics at high-dose through three trimesters were infrequent in the study population, and most pregnant women were continuously exposed to low-dose PVAs across pregnancy. A total of 4.5% samples were showed hazard index values exceeding 1 during entire pregnancy. Urinary levels of antibiotics associated with residence, maternal age and education, pre-pregnancy BMI, household income and gestational week, especially vary by sampling seasons. Taken together, most pregnant women were frequently exposure to low-dose PVAs across pregnancy and some were in a health risk associated with the disturbance of gut microbiota. Multiple measurements of urinary antibiotic concentrations are essential to more accurate charactering the exposure levels during pregnancy. Several predictors of urinary antibiotics should be taken into consideration in future researches.
Based on a medical record or questionnaire survey approach, previous epidemiological studies have investigated associations between maternal antibiotic exposure during pregnancy and childhood ...allergic diseases. However, biomonitoring studies on the prenatal low-dose antibiotic exposure, mainly from the environment and contaminated food, and in relation to children allergic diseases, are missing.
This research aimed to examine the associations between prenatal low-dose antibiotic exposure measured at multiple time points and children current allergic diseases at 4 years of age.
The current study including 2453 mother-child pairs was based on the Ma’anshan Birth Cohort study. Selected 41 antibiotics and their two metabolites, which including human antibiotics (HAs), preferred as human antibiotics (PHAs), veterinary antibiotics (VAs) and preferred as veterinary antibiotics (PVAs), in urine samples from 2453 pregnant women were biomonitored through liquid chromatography-triple quadrupole tandem mass spectrometry. Information on children current allergic diseases were collected via validated questionnaires. Generalized estimating equation were used to explore the associations between the repeated measurements of maternal urinary antibiotic over three trimesters and current allergic diseases in children.
The detection rates of nine individual antibiotics in the three trimester during pregnancy are greater than 10%, and the 90th percentile concentration of the detected antibiotics ranges from 0.07 to 22.34 µg/g, and the 95th percentile concentration ranges from 0.17 to 59.57 µg/g. Among the participants, each one-unit concentration increment of sulfamethazine (adjusted OR=1.28, 95% CI: 1.10, 1.49, P-FDR=0.014) in the first trimester and ciprofloxacin (adjusted OR=1.17, 95% CI: 1.07, 1.28, P-FDR=0.008) in the second trimester were associated with an increased risk of current eczema in children. In the third trimester, each one-unit concentration increment of oxytetracycline (adjusted OR=1.90, 95% CI: 1.30, 2.78, P-FDR=0.014) was associated with an increased risk of current asthma in children. Gender-stratified analyses demonstrated that no gender differences were observed in the associations between prenatal antibiotic exposure and current allergic diseases in children.
Maternal exposure to certain specific VAs or PVAs (sulfamethazine, ciprofloxacin and oxytetracycline) in different trimesters was associated with an increased risk of current asthma and current eczema in 4-year-old children. No gender differences were found in these associations. Further studies are warranted to confirm our findings and explore the potential mechanisms.
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•Pregnant women were commonly exposed to low-dose antibiotics during pregnancy.•Sulfamethazine exposure (1st trimester) increases the risk of eczema in children.•Ciprofloxacin exposure (2nd trimester) elevates the risk of eczema in children.•Oxytetracycline exposure (3nd trimester) increases the risk of asthma in children.•No gender differences were found in these associations.
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.
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-1β, 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.
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 (β = - 0.53; 95% CI, - 0.92 to - 0.15), IL-6 (β = - 0.58; 95% CI, - 0.97 to - 0.19), TNF-α (β = - 0.37; 95% CI, - 0.71 to - 0.02), and IFN-γ (β = - 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.
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.
•Co-consumption of fast foods and sugar-sweetened beverages (SSBs) increased the risk of mental health problem in adolescents.•14,500 adolescents across 4 provinces of China were included in this ...study.•This is a first-ever, nationwide study on the effects of co-consumption of fast foods and SSBs on psychological symptoms in Chinese adolescents.•Association was assessed in quantile regression model and adjusted for covariates.
Background: Although fast food and sugar-sweetened beverages (SSBs) consumption have been closely linked to childhood and adolescent obesity, the data regarding their co-consumption and relationship to mental health remains controversial.
Methods: A multi-centered population-based survey was conducted among Chinese adolescents from grades 7 to 12. Data about participants’ consumption of fast foods and SSBs were obtained from self-reported questionnaires. Psychological symptoms were assessed using the Multi-dimensional Sub-health Questionnaire of Adolescents (MSQA). The association between co-consumption of fast food and SSBs and psychological symptoms was assessed using quantile regression analysis, adjusting for covariates.
Results: Approximately one-fifth of the 14,500 participants reported psychological symptoms. The regression coefficient (β) value increased as the quantile of fast food, SSBs, and co-consumption increased in the quantile regression model, and the model had an excellent goodness-of-fit (F = 192.51, p < 0.001). In the interaction model, fast food and SSBs in combination were associated with greater odds of psychological symptoms (aOR = 1.90, 95% CI: 1.69, 2.12). The synergy index, relative excess risk of interaction, and attributable proportions were 1.86 (95% CI: 1.17, 2.96), 0.4 (95% CI: 0.20, 0.63), and 0.22 (95% CI: 0.11, 0.33), respectively.
Limitations: Information bias is inevitable in self-reported data among participants. The ability to assess causal relationships is reduced by a cross-sectional study design.
Conclusions: Our findings suggest that co-consumption of fast food and SSBs was cross-sectionally associated with mental health problems among adolescents.
Only few studies have assessed the health effects due to preconception exposure to antibiotics among childbearing couples. This study investigated the status of preconception exposure to antibiotics ...among childbearing couples in Anhui, associated with health risks, and influencing factors. Overall, 1500 childbearing couples were randomly selected from the Reproductive Health of Childbearing Couples - Anhui Cohort (RHCC-AC). The urinary levels of 40 antibiotics and 2 metabolites were determined, and specific gravity (SG) adjusted concentrations of antibiotics were measured to assess health risks. Generalized linear models were used to assess the associations of urinary SG-adjusted concentration of antibiotics with demographic parameters and diet frequency. The total detection rates of all antibiotics were 98.9 % and 99.3 % in wives and husbands, respectively. The detection rates of veterinary antibiotics (VAs) and preferred as VAs (PVAs) were above 90 %. Among eight antibiotics, sulfonamides (95.1 %) and fluoroquinolones (87.6 %) had the highest detection rates in couples. Approximately four-fifths of couples were simultaneously exposed to at least three different antibiotics, and more than half of them were exposed to low concentrations of antibiotics. 8.9 % and 9.2 % of wives and husbands had hazard index value of antibiotics exposure greater than 1. Antibiotic concentrations were associated with residence, sampling season, and diet frequency. In Anhui, nearly 98 % of childbearing couples have environmental exposure to antibiotics, and VAs and PVAs are the primary antibiotics. More than 8 % of couples had health risks due to antibiotic exposure. Several potential determinants of urinary antibiotics deserve more attention in future research.
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•Over 98 % of childbearing couples are exposed to multiple environmental antibiotics.•Veterinary antibiotics (VAs) and preferred as VAs are the main exposed antibiotics.•One third of couples are simultaneously exposed to four usage antibiotics.•Exposure to antibiotics posed health risks to 8.9 % and 9.2 % of couples.•Urinary antibiotic levels were associated with residence, sampling season and diet.
Based on self-report questionnaires, two previous epidemiological studies investigated the association between the exposure of women to antibiotics and their fertility. However, biomonitoring studies ...on low-dose antibiotic exposure, mainly from food and water, and its relation to the risk of infertility are missing.
Based on a case-control study design, 302 women with infertility (144 primary infertility, 158 secondary infertility) and 302 women with normal fertility, all aged 20–49 years, were recruited from Anhui Province, China, in 2020 and 2021. A total of 41 common antibiotics and two antibiotic metabolites in urine samples were determined by liquid chromatography–triple quadrupole tandem mass spectrometry (LC-QqQ-MS/MS).
Twenty-eight antibiotics with detection rates from 10% to 100% in both cases (median concentration: ∼2.294 ng/mL) and controls (∼1.596 ng/mL) were included in the analysis. Logistic regression analysis revealed that after controlling for confounding factors, high concentrations of eight individual antibiotics (sulfamethoxazole, sulfaclozine, sulfamonomethoxine, penicillin G, chlorotetracycline, ofloxacin, norfloxacin, and cyadox) and four antibiotic classes (sulfonamides, tetracyclines, quinoxalines, and veterinary antibiotics) were related to a high risk of female infertility, with odds ratios (ORs) ranging from 1.30 to 2.86, except for chlorotetracycline (OR = 6.34), while another nine individual antibiotics (sulfamethazine, azithromycin, cefaclor, amoxicillin, oxytetracycline, pefloxacin, sarafloxacin, enrofloxacin, and florfenicol) and classes of chloramphenicol analogs and human antibiotics were related to a reduced risk of infertility, with ORs ranging from 0.70 to 0.20. Based on restricted cubic spline models after controlling for confounding factors, we observed that the relationship between all of the above protective antibiotics and infertility was nonlinear: A certain concentration could reduce the risk of female infertility while exceeding a safe dose could increase the risk of infertility.
These results provide preliminary evidence that the effects of antibiotics on female fertility vary based on the active ingredient and usage and imply the importance of exposure dose. Future studies are needed to verify these results by controlling for multiple confounding factors.
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•Women of childbearing age were exposed to low levels of multiple antibiotics.•Association of antibiotics with female infertility depends on the use and active ingredients.•Some antibiotics, like veterinary antibiotics, increased the risk of infertility.•Some antibiotics, like human antibiotics, reduced the risk of infertility in safe dose.
Abstract
Background
This study aims to investigate the association between sleep quality and infertility among women and to explore the mediating effects of DNA methylation in this association.
...Methods
This study is a population-based case–control study. The relationship between sleep quality and infertility was investigated in women with anovulatory infertility (
n
= 43) and healthy controls (
n
= 43). Genome-wide DNA methylation was profiled from peripheral blood samples using the Illumina Infinium Human Methylation 850k BeadChip. Differentially methylated CpGs between cases and controls were identified using the
ChAMP
R package. The mediating effect of DNA methylation between sleep quality and infertility among women was investigated using the Bayesian estimation method provided by the R package “mediation”.
Results
The survey included 86 women of reproductive age, with 43 participants each in the case and control groups. The average age of the women was 27.6 ± 2.8 years (case group: 27.8 ± 3.0 years, control group: 27.4 ± 2.7 years). A total of 262 differentially methylated CpGs corresponding to 185 genes were identified. Difficulty falling asleep was a risk factor for infertility in women (
OR
= 3.69, 95%
CI
= 1.14, 11.99), and a causal mediation effect of DNA methylation CpGs was found. The mediating effect coefficient for cg08298632 was 0.10 (95%
CI
= 0.01–0.22), and the proportion of the total effect mediated by this methylation site increased to 64.3%.
Conclusion
These results suggest that DNA methylation CpGs (cg08298632) play a significant role in the relationship between difficulty falling asleep and infertility in females. These findings contribute to our understanding of the underlying mechanisms that connect difficulty falling asleep and infertility in women. Further studies are necessary to fully understand the biological significance and potential therapeutic applications of these findings. The identified DNA methylation sites provide new and valuable insights and potential targets for future studies aiming to prevent and treat female infertility.
Growing evidence has indicated the association of clinical antibiotic use with abnormal blood lipid levels; however, no epidemiological study has examined the relationship of antibiotic exposure, ...probably derived from food chains, with blood lipid levels. This study investigated the relationships of urinary antibiotic levels with blood lipid levels and dyslipidemias in the older population. Baseline data of 960 participants from the Cohort of Elderly Health and Environment Controllable Factors were used in the present study. High-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was performed to detect antibiotic residues in the urine samples of the participants. Our findings revealed that each 1 μg/g increase in enrofloxacin and ciprofloxacin levels was associated with an increase of 0.084 (95 % confidence interval (CI): 0.030, 0.139) and 0.049 (95 % CI: 0.012, 0.086) in triglyceride levels, respectively. Enrofloxacin was associated with an increased risk of hypertriglyceridemia. Each 1 μg/g increase in the enrofloxacin level corresponded to an increase of 0.052 (95 % CI: 0.006, 0.098) in the low-density lipoprotein cholesterol level. Furthermore, florfenicol exposure increased the risks of both hyperbetalipoproteinemia and hypoalphalipoproteinemia. By contrast, each 1 μg/g increase in sulfaclozine and doxycycline levels was associated with a − 0.062 (95 % CI: −0.111, −0.020), and − 0.083 (95 % CI: −0.160, −0.007) decrease in total cholesterol levels, respectively. Sulfaclozine was closely related to a decreased risk of hypercholesterolemia. Stratification analysis revealed specific differences in the correlation between antibiotic exposure and lipid levels based on the waist circumference (WC) values of the participants. Except for sulfaclozine and doxycycline, other antibiotics exerted adverse effects on lipid levels and increased dyslipidemia prevalence. The older participants with higher WC values were vulnerable to antibiotic exposure. Therefore, an appropriate understanding of the epidemiological attributes of antibiotic residues is indispensable to prevent abdominal obesity in the older population.
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•Doxycycline exposure was negatively correlated with TG levels.•Doxycycline exposure was linked to a reduced risk of hypertriglyceridemia.•Macrolide exposure was related to hypercholesterolemia and hypertriglyceridemia.•WC discrepancy intervened the associations between antibiotics and blood lipids.
•Approximately 25% of preschoolers drink sugar-sweetened beverages (SSB) one or more time per day in China.•High consumption frequency of SSB is positively associated with behavioral problems among ...preschoolers.•No gender differences were found in these associations.
Previous researches showed a positive association between sugar-sweetened beverages (SSB) and behavioral problems, but there is a little known in Chinese preschoolers.
A population based survey was conducted in 109 kindergartens, in 11 cities across China. Children's SSB consumption was assessed by questionnaires completed by caregivers. The Strengths and Difficulties Questionnaire (SDQ) and the Clancy Autism Behavior Scale (CABS) were used to assessing the children's behavioral problems.
The prevalence of SSB consumption ≥ 1 time/day was 24.9%. The adjusted odds ratios (95% confidence interval) of having elevated total difficulties by increasing levels of SSB consumption were 1.00, 1.13 (1.05, 1.22) and 1.24 (1.10, 1.41) (P for trend < 0.001), respectivly. Similar results were found in emotional symptoms, conduct problems, peer problems, and CABS. No significantly increased the risk of hyperactivity and prosocial were observed for higher SSB consumption. No gender differences were found in these associations.
This is a cross-sectional survey and the causal relationship is unclear.
Higher SSB consumption is positively associated with behavioral problems among preschoolers in China.
Biomonitoring methods can be used to measure exposure to antibiotics in the general population; however, epidemiological data on the associations between urinary antibiotic levels and the cardiac ...profiles of enzymes lactate dehydrogenase, creatine kinase, and creatine kinase isoenzyme in older adults remain sparse. We investigated these associations in 990 individuals from the Cohort of Elderly Health and Environment Controllable Factors. Antibiotic residues in urine samples were analyzed using high-performance liquid chromatography–tandem mass spectrometry. Urinary levels of 34 antibiotics were measured. The participants’ cardiac enzyme profiles were influenced by sex, age, marital status, education level, cohabitation status, physical activity, dietary structure, body mass index, depression presence and salt, sugar, and oil consumption (
P
< 0.05). Oxytetracycline, tetracycline, doxycycline, sulfaclozine, and, florfenicol concentrations were negatively associated with the risk of having an abnormal cardiac enzyme profile. Older adults exposed to higher concentrations of norfloxacin had a higher risk of LDH anomalies. After antibiotics were classified, we identified associations between exposure to chloramphenicols, sulfonamides, or veterinary antibiotics and a lower risk of having an abnormal cardiac enzyme profile. Obtaining an accurate epidemiological profile of antibiotic exposure is indispensable for the prevention and detection of cardiac enzyme profile abnormalities in older adults.
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