Associations of inflammation related prenatal adversities with neurodevelopment of offspring in one year: a longitudinal prospective birth cohort study.

BACKGROUND: The recent Maternal Immune Activation (MIA) theory suggests maternal systemic inflammation may serve as a mediator in associations between prenatal maternal adversities and neurodevelopmental diseases in offspring. Given the co-exposure to multiple adversities may be experienced by pregnant person, it is unclear whether a quantitative index can be developed to characterize the inflammation related exposure level, and whether this index is associated with neurodevelopmental delays in offspring. METHODS: Based on Jiangsu Birth Cohort (JBC), a total of 3051 infants were included in the analysis. Inflammation related Prenatal Adversity Index (IPAI) was constructed using maternal data. Neurodevelopmental outcomes were assessed using the Bayley Scales of Infant and Toddler Development, third edition, screening test in one year. Multivariate linear regression and Poisson regression model were performed to analyze the associations between IPAI and neurodevelopment in offspring. RESULTS: Compared with "low IPAI" group, offspring with "high IPAI" have lower scores of cognition, receptive communication, expressive communication, and fine motor. The adjusted ß were - 0.23 (95%CI: -0.42, -0.04), -0.47 (95%CI: -0.66, -0.28), -0.30 (95%CI: -0.49, -0.11), and - 0.20 (95%CI: -0.33, -0.06). Additionally, the elevated risk for noncompetent development of cognition and receptive communication among "high IPAI" group was observed. The relative risk [RR] and 95% confidence interval [CI] were 1.35 (1.01, 1.69) and 1.37 (1.09, 1.72). CONCLUSIONS: Our results revealed a significant association between higher IPAI and lower scores across cognition, receptive communication, expressive communication, and fine motor domains, and an increased risk of noncompetent development in the cognition and receptive communication domains.

Prenatal Parental Exposure to Metals and Birth Defects: A Prospective Birth Cohort Study.

While maternal exposure to high metal levels during pregnancy is an established risk factor for birth defects, the role of paternal exposure remains largely unknown. We aimed to assess the associations of prenatal paternal and maternal metal exposure and parental coexposure with birth defects in singletons. This study conducted within the Jiangsu Birth Cohort recruited couples in early pregnancy. We measured their urinary concentrations for 25 metals. A total of 1675 parent-offspring trios were included. The prevalence of any birth defects among infants by one year of age was 7.82%. Paternal-specific gravity-corrected urinary concentrations of titanium, vanadium, chromium, manganese, cobalt, nickel, copper, and selenium and maternal vanadium, chromium, nickel, copper, selenium, and antimony were associated with a 21-91% increased risk of birth defects after adjusting for covariates. These effects persisted after mutual adjustment for the spouse's exposure. Notably, when assessing the parental mixture effect by Bayesian kernel machine regression, paternal and maternal chromium exposure ranked the highest in relative importance. Parental coexposure to metal mixture showed a pronounced joint effect on the risk of overall birth defects, as well as for some specific subtypes. Our findings suggested a couple-based prevention strategy for metal exposure to reduce birth defects in offspring.

Maternal Hypertensive Disorder in Pregnancy and Childhood Strabismus in Offspring.

Importance: Maternal hypertensive disorder in pregnancy (HDP) might affect ocular health in offspring; however, its association with strabismus remains unclear. Objective: To examine the association of maternal HDP with overall and type-specific strabismus in offspring. Design, Setting, and Participants: In the Jiangsu Birth Cohort study, a population-based study in China, pregnant women were recruited from April 24, 2014, to November 30, 2018. A total of 6195 offspring had maternal HDP diagnosis information, of whom 3078 were excluded due to having no information on ocular alignment or due to having ocular diseases other than strabismus or refractive error. Offspring underwent ocular examinations at 3 years of age, completed May 21, 2022. Data were analyzed from May 28, 2022, through December 15, 2023. Exposure: Maternal HDP, categorized into hypertension and preeclampsia or with blood pressure (BP) well controlled (systolic BP, <130; diastolic BP, <80 mm Hg) and poorly controlled (systolic BP, ≥130; diastolic BP, ≥80 mm Hg). Main Outcomes and Measures: The primary outcome was the incidence of strabismus in offspring. Poisson generalized linear mixed models were used to estimate the association between maternal HDP and strabismus. Results: Among the included 3117 children (mean [SD] age, 36.30 [0.74] months; 1629 boys [52.3%]), 143 (4.6%) were exposed to maternal HDP and 368 (11.8%) had strabismus. Offspring exposed to maternal HDP had an 82% increased risk of overall strabismus (relative risk [RR], 1.82 [95% CI, 1.21-2.74]), an 82% increased risk of exophoria (RR, 1.82 [95% CI, 1.11-3.00]), and a 136% increased risk of intermittent exotropia (RR, 2.36 [95% CI, 1.13-4.93]) compared with unexposed offspring. When considering the type of maternal HDP, the risk for all strabismus was high for offspring exposed to preeclampsia (RR, 2.38 [95% CI, 1.39-4.09]) compared with unexposed offspring. When considering the BP control level of maternal HDP, the risk for all strabismus was high for offspring born to mothers with HDP and poorly controlled BP (RR, 2.07 [95% CI, 1.32-3.24]) compared with unexposed offspring. Conclusions and Relevance: These findings suggest that maternal HDP is associated with an increased risk of offspring strabismus. Early screening of strabismus might be recommended for offspring with maternal HDP. Further exploration of the underlying mechanism of the association between HDP and strabismus is warranted.

Association of prenatal multiple metal exposures with child neurodevelopment at 3 years of age: A prospective birth cohort study.

Prenatal exposures to toxic metals and trace elements have been linked to childhood neurodevelopment. However, existing evidence remains inconclusive, and further research is needed to investigate the mixture effects of multiple metal exposures on childhood neurodevelopment. We aimed to examine the associations between prenatal exposure to specific metals and metal mixtures and neurodevelopment in children. In this prospective cohort study, we used the multivariable linear regressions and the robust modified Poisson regressions to explore the associations of prenatal exposure to 25 specific metals with neurodevelopment among children at 3 years of age in 854 mother-child pairs from the Jiangsu Birth Cohort (JBC) Study. The Bayesian kernel machine regression (BKMR) was employed to assess the joint effects of multiple metals on neurodevelopment. Prenatal manganese (Mn) exposure was negatively associated with the risk of non-optimal cognition development of children, while vanadium (V), copper (Cu), zinc (Zn), antimony (Sb), cerium (Ce) and uranium (U) exposures were positively associated with the risk of non-optimal gross motor development. BKMR identified an interaction effect between Sb and Ce on non-optimal gross motor development. Additionally, an element risk score (ERS), representing the mixture effect of multiple metal exposures including V, Cu, Zn, Sb, Ce and U was constructed based on weights from a Poisson regression model. Children with ERS in the highest tertile had higher probability of non-optimal gross motor development (RR = 2.37, 95 % CI: 1.15, 4.86) versus those at the lowest tertile. Notably, Sb [conditional-posterior inclusion probabilities (cPIP) = 0.511] and U (cPIP = 0.386) mainly contributed to the increased risk of non-optimal gross motor development. The findings highlight the importance of paying attention to the joint effects of multiple metals on children's neurodevelopment. The ERS score may serve as an indicator of comprehensive metal exposure risk for children's neurodevelopment.

Impact of low-dose aspirin exposure on obstetrical outcomes: a meta-analysis.

OBJECTIVE: To assess the impact of low-dose aspirin (LDA) on obstetrical outcomes through a meta-analysis of placebo-controlled randomized controlled trials (RCTs). METHODS: A systematic search of the PubMed, Cochrane Library, Web of Science and Embase databases from inception to January 2024 was conducted to identify studies exploring the role of aspirin on pregnancy, reporting obstetrical-related outcomes, including preterm birth (PTB, gestational age <37 weeks), small for gestational age (SGA), low birth weight (LBW, birthweight < 2500g), perinatal death (PND), admission to the neonatal intensive care unit (NICU), 5-min Apgar score < 7 and placental abruption. Relative risks (RRs) were estimated for the combined outcomes. Subgroup analyses were performed by risk for preeclampsia (PE), LDA dosage (<100 mg vs. ≥100 mg) and timing of onset (≤20 weeks vs. >20 weeks). RESULTS: Forty-seven studies involving 59,124 participants were included. Compared with placebo, LDA had a more significant effect on low-risk events such as SGA, PTB and LBW. Specifically, LDA significantly reduced the risk of SGA (RR = 0.91, 95% CI: 0.87-0.95), PTB (RR = 0.93, 95% CI: 0.89-0.97) and LBW (RR = 0.94, 95% CI: 0.89-0.99). For high-risk events, LDA significantly lowered the risk of NICU admission (RR = 0.93, 95% CI: 0.87-0.99). On the other hand, LDA can significantly increase the risk of placental abruption (RR = 1.72, 95% CI: 1.23-2.43). Subgroup analyses showed that LDA significantly reduced the risk of SGA (RR = 0.86, 95% CI: 0.77-0.97), PTB (RR = 0.93, 95% CI: 0.88-0.98) and PND (RR = 0.65, 95% CI: 0.48-0.88) in pregnant women at high risk of PE, whereas in healthy pregnant women LDA did not significantly improve obstetrical outcomes, but instead significantly increased the risk of placental abruption (RR = 5.56, 95% CI: 1.92-16.11). In pregnant women at high risk of PE, LDA administered at doses ≥100 mg significantly reduced the risk of SGA (RR = 0.77, 95% CI: 0.66-0.91) and PTB (RR = 0.56, 95% CI: 0.32-0.97), but did not have a statistically significant effect on reducing the risk of NICU, PND and LBW. LDA started at ≤20 weeks significantly reduced the risk of SGA (RR = 0.76, 95% CI: 0.65-0.89) and PTB (RR = 0.56, 95% CI: 0.32-0.97). CONCLUSIONS: To sum up, LDA significantly improved neonatal outcomes in pregnant women at high risk of PE without elevating the risk of placental abruption. These findings support LDA's clinical application in pregnant women, although further research is needed to refine dosage and timing recommendations.

Assisted reproductive technology and neurodevelopment in children at 1 year of age: a longitudinal birth cohort study.

BACKGROUND: With remarkable advancements in assisted reproductive technology (ART), the number of ART-conceived children continues to increase. Despite increased research investigating the outcomes of ART children, evidence on neurodevelopment remains controversial. OBJECTIVE: The aim of this study was to investigate the association between ART use and neurodevelopment in children at 1 year of age and to determine whether the characteristics of parental infertility and specific ART procedures affect neurodevelopment in children. STUDY DESIGN: The Jiangsu Birth Cohort enrolled couples who received ART treatment and who conceived spontaneously (2014-2020) in Jiangsu Province, China. In this study, we included 3531 pregnancies with 3840 cohort children who completed neurodevelopment assessment at 1 year of age, including 1906 infants conceived by ART (including 621 twins). Poisson regressions were fitted to estimate unadjusted and adjusted risk ratios (RRs) and 95% confidence intervals (CIs) for ART use with neurodevelopmental outcomes (cognition, receptive communication, expressive communication, fine motor, and gross motor) in children. RESULTS: Among singletons, ART use was associated with a 24% to 34% decrease in the risk for noncompetent development in 3 domains (cognition, adjusted RR, 0.66; 95% CI, 0.53-0.82; receptive communication, 0.76; 0.64-0.91; expressive communication, 0.69; 0.51-0.93) after adjustment for conventional covariates. However, an inverse association was observed in the gross motor domain, with ART singletons having a greater risk of being noncompetent in gross motor development than their non-ART counterparts (adjusted RR, 1.41; 95% CI, 1.11-1.79). Compared with singletons, twins resulting from ART treatment demonstrated compromised neurodevelopment in several domains. Furthermore, we continued to observe that the transfer of 'poor' quality embryos was associated with greater risks for noncompetent development in receptive communication (adjusted RR, 1.50; 95% CI, 1.05-2.14) and gross motor domains (1.55; 1.02-2.36) among ART singletons. CONCLUSION: These results generally provide reassuring evidence among singletons born after ART in the cognition, communication, and fine motor domains, but drawn attention to their gross motor development. The quality of transferred embryos in ART treatment might be associated with offspring neurodevelopment; however, the potential associations warrant further validation in independent studies, and the clinical significance needs careful interpretation.

Phthalate and DINCH exposure and ovarian reserve markers among women seeking infertility care.

Phthalate exposure can adversely impact ovarian reserve, yet investigation on the influence of its alternative substance, the non-phthalate plasticizer diisononyl-cyclohexane-1,2-dicarboxylate (DINCH), on ovarian reserve is very sparce. We aimed to investigate the associations of phthalate and DINCH exposure as well as their combined mixture with ovarian reserve. This present study included 657 women seeking infertility care in Jiangsu, China (2015-2018). Urine samples during enrollment prior to infertility treatment were analyzed using high-performance liquid chromatography-isotope dilution tandem mass spectrometry (UPLC-MS/MS) to quantify 17 phthalate metabolites and 3 DINCH metabolites. Multivariate linear regression models, Poisson regression models and weighted quantile sum (WQS) regression were performed to access the associations of 17 urinary phthalate metabolites and 3 DINCH metabolites with ovarian reserve markers, including antral follicle count (AFC), anti-Mullerian hormone (AMH), and follicle-stimulating hormone (FSH). We found that the most conventional phthalates metabolites (DMP, DnBP, DiBP, DBP and DEHP) were inversely associated with AFC, and the DINCH metabolites were positively associated with serum FSH levels. The WQS index of phthalate and DINCH mixtures was inversely associated with AFC (% change = -8.56, 95 % CI: -12.63, -4.31) and positively associated with FSH levels (% change =7.71, 95 % CI: 0.21, 15.78). Our findings suggest that exposure to environmental levels of phthalate and DINCH mixtures is inversely associated with ovarian reserve.

Relative effectiveness of a heterologous booster dose with adenovirus type 5 vectored COVID-19 vaccine versus three doses of inactivated COVID-19 vaccine in adults during a nationwide outbreak of omicron predominance, in China: a retrospective, individually matched cohort-control study.

Effectiveness of heterologous booster regimes with ad5 vectored COVID-19 vaccine in a large, diverse population during the national-scale outbreak of SARS-CoV-2 omicron predominance in China has not been reported, yet. We conducted a large-scale cohort-control study in six provinces in China, and did a retrospective survey on the COVID-19 attack risk during this outbreak. Participant aged ≥18 years in five previous trials who were primed with 1 to 3 doses of ICV received heterologous booster with either intramuscular or orally inhaled ad5 vectored COVID-19 vaccine were included in the heterologous-trial cohort. We performed propensity score-matching at a ratio of 1:4 to match participants in the heterologous-trial cohort individually with the community individuals who received three-dose of ICV as a control (ICV-community cohort). From February 4 to April 10, 2023, 41504 (74.5%) of 55710 individuals completed the survey. The median time since the most recent vaccination to the onset of the symptoms of COVID-19 was 303.0 days (IQR 293.0-322.0). The attack rate of COVID-19 in the heterologous-trial cohort was 55.8%, while that in the ICV-community cohort was 64.6%, resulting in a relative effectiveness of 13.7% (95% CI 11.9 to 15.3). In addition, a higher relative effectiveness against COVID-19 associated outpatient visits, and admission to hospital was demonstrated, which was 25.1% (95% CI 18.9 to 30.9), and 48.9% (95% CI 27.0 to 64.2), respectively. The heterologous booster with ad5 vectored COVID-19 vaccine still offered some additional protection in preventing COVID-19 breakthrough infection versus homologous three-dose regimen with ICV, 10 months after vaccination.

Inter- and trans-generational impacts of real-world PM2.5 exposure on male-specific primary hypogonadism.

Exposure to PM2.5, a harmful type of air pollution, has been associated with compromised male reproductive health; however, it remains unclear whether such exposure can elicit transgenerational effects on male fertility. Here, we aim to examine the effect of paternal exposure to real-world PM2.5 on the reproductive health of male offspring. We have observed that paternal exposure to real-world PM2.5 can lead to transgenerational primary hypogonadism in a sex-selective manner, and we have also confirmed this phenotype by using an external model. Mechanically, we have identified small RNAs (sRNAs) that play a critical role in mediating these transgenerational effects. Specifically, miR6240 and piR016061, which are present in F0 PM sperm, regulate intergenerational transmission by targeting Lhcgr and Nsd1, respectively. We have also uncovered that piR033435 and piR006695 indirectly regulate F1 PM sperm methylation by binding to the 3'-untranslated region of Tet1 mRNA. The reduced expression of Tet1 resulted in hypermethylation of several testosterone synthesis genes, including Lhcgr and Gnas, impaired Leydig cell function and ultimately led to transgenerational primary hypogonadism. Our findings provide insights into the mechanisms underlying the transgenerational effects of paternal PM2.5 exposure on reproductive health, highlighting the crucial role played by sRNAs in mediating these effects. The findings underscore the significance of paternal pre-conception interventions in alleviating the adverse effects of environmental pollutants on reproductive health.

Maternal Dietary Cholesterol and Egg Intake during Pregnancy and Large-for-Gestational-Age Infants: A Prospective Cohort Study.

BACKGROUND: Cholesterol plays a vital role in fetal growth and development during pregnancy. There remains controversy over whether pregnant females should limit their cholesterol intake. OBJECTIVES: The objective of this study was to investigate the association between maternal dietary cholesterol intake during pregnancy and infant birth weight in a Chinese prospective cohort study. METHODS: A total of 4146 mother-child pairs were included based on the Jiangsu Birth Cohort study. Maternal dietary information was assessed with a semiquantitative food-frequency questionnaire. Birth weight z-scores and large-for-gestational-age (LGA) infants were converted by the INTERGROWTH-21st neonatal weight-for-gestational-age standard. Poisson regression and generalized estimating equations were employed to examine the relationships between LGA and maternal dietary cholesterol across the entire pregnancy and trimester-specific cholesterol intake, respectively. RESULTS: The median intake of maternal total dietary cholesterol during the entire pregnancy was 671.06 mg/d, with eggs being the main source. Maternal total dietary cholesterol and egg-sourced cholesterol were associated with an increase in birth weight z-score, with per standard deviation increase in maternal total and egg-sourced dietary cholesterol being associated with an increase of 0.16 [95% confidence interval (CI): 0.07, 0.25] and 0.06 (95% CI: 0.03, 0.09) in birth weight z-score, respectively. Egg-derived cholesterol intake in the first and third trimesters was positively linked to LGA, with an adjusted relative risk of 1.11 (95% CI: 1.04, 1.18) and 1.09 (95% CI: 1.00, 1.18). Compared with mothers consuming ≤7 eggs/wk in the third trimester, the adjusted relative risk for having an LGA newborn was 1.37 (95% CI: 1.09, 1.72) for consuming 8-10 eggs/wk and 1.45 (95% CI: 1.12, 1.86) for consuming >10 eggs/wk (P-trend = 0.015). CONCLUSIONS: Maternal total dietary cholesterol intake, as well as consuming over 7 eggs/wk during pregnancy, displayed significant positive relationships with the incidence of LGA, suggesting that mothers should avoid excessive cholesterol intake during pregnancy to prevent adverse birth outcomes.

Effect of thyroid function on offspring neurodevelopment in people receiving ART therapy: a prospective cohort study.

CONTEXT: Adequate maternal thyroid hormone is vital for fetal neurodevelopment. Abnormal thyroid function can cause developmental defects in offspring from spontaneous pregnancies; however, research in assisted reproduction is lacking. OBJECTIVES: To investigate the association between thyroid disorders and offspring neurodevelopment from assisted reproduction. DESIGN: Prospective cohort study. SETTING AND PARTICIPANTS: In this prospective and longitudinal birth cohort study (Jiangsu, China), we included 729 women who had their thyroid function tested before ART cycle and delivered liveborn babies between November 2015 and June 2020. MAIN OUTCOME MEASURES: Maternal thyroid function was assessed by measuring thyroid antibodies, free thyroxine, and serum thyroid-stimulating hormone. The third edition Bayley Scales of Infant and Toddler Development screening test (Bayley-III screening test) is used to assess the infant's neurodevelopment. RESULTS: In multivariate corrected linear regression analysis, infants of women with subclinical hypothyroidism demonstrated a significantly lower receptive communication score (ß = -0.63, 95% CI [-1.12, -0.14], P = 0.013), with stratified analysis showing a significant association among female offspring (ß = -0.87, 95% CI [-1.59, -0.15], P = 0.018) but null association among male offspring (ß = -0.44, 95% CI [-1.03, 0.15], P = 0.145). No significant differences were found in assisted pregnancy population with normal thyroid function and positive antibodies according to the diagnostic cut-offs applied to normal pregnant women. CONCLUSIONS: Subclinical hypothyroidism in assisted pregnancies correlates with lower communication scores in 1-year-olds, especially in girls. Recommending medication for subclinical hypothyroidism throughout, regardless of thyroid autoantibody status.

Association of Breastfeeding and Neonatal Jaundice With Infant Neurodevelopment.

INTRODUCTION: Exclusive breastfeeding is advantageous for infant neurodevelopment. Nevertheless, insufficient human milk supply in exclusively breastfed infants may elevate the risk of neonatal jaundice, which can potentially result in neurological harm. Whether mothers should adhere to exclusive breastfeeding in infants with neonatal jaundice remains unclear. METHODS: Data comes from the Jiangsu Birth Cohort (JBC), a prospective and longitudinal birth cohort study in China. A total of 2,577 infants born from November 2017 to March 2021 were included in the analysis. Multivariate linear regression models were used to analyze the associations between breastfeeding status, neonatal jaundice, and their interaction with infant neurodevelopment. Analysis was performed in 2022. RESULTS: Compared with "exclusive breastfeeding," fine motor scores of infants were lower for "mixed feeding" (ßadj, -0.16; 95% CI, -0.29 to -0.03; p=0.016) and "no breastfeeding" (ßadj, -0.41; 95% CI, -0.79 to -0.03; p=0.034). Compared with "no neonatal jaundice," infants with "severe neonatal jaundice" had lower scores for cognition (ßadj, -0.44; 95% CI, -0.66 to -0.23; p<0.001) and fine motor (ßadj, -0.19; 95% CI, -0.35 to -0.03; p=0.024). In infants with severe neonatal jaundice, the termination of exclusive breastfeeding before 6 months was associated with worse cognition (ßadj, -0.28; 95% CI, -0.57 to 0.01), while this association was not observed in those without neonatal jaundice (ßadj, 0.09; 95% CI, -0.26 to 0.43). CONCLUSIONS: Exclusive breastfeeding for the first 6 months is beneficial to the neurodevelopment of infants, especially in those with severe neonatal jaundice.

Association of maternal hypertensive disorders in pregnancy with infant neurodevelopment.

Inconsistent findings have been reported regarding the associations between hypertensive disorders in pregnancy (HDP) and infant neurodevelopment. Leveraging data from the Jiangsu Birth Cohort, in the present study, we re-visited such associations in one-year-old infants from 2576 singleton pregnancies and 261 twin pregnancies. We first assessed infant neurodevelopment by the Bayley Scales of Infant and Toddler Development Screening Test (the Third Edition), and then estimated its association with maternal HDP using general linear regression models and Poisson regression models. In singleton pregnancies, compared with mothers unexposed to HDP, infants born to mothers with chronic hypertension exhibited a lower score ( ß, -0.67; 95% confidence interval [CI], -1.19--0.15) and a higher risk of "non-optimal" gross motor development (risk ratio [RR], 2.21; 95% CI, 1.02-4.79); in twin pregnancies, infants born to mothers with HDP exhibited lower scores in cognition ( ß, -0.49; 95% CI, -0.96--0.01), receptive communication ( ß, -0.55; 95% CI, -1.03--0.06), and gross motor ( ß, -0.44; 95% CI, -0.86--0.03), and at a higher risk of "non-optimal" gross motor development (RR, 2.12; 95% CI, 1.16-3.88). These findings indicate that infants born to mothers with HDP may have inferior neurodevelopment outcomes at the age of one year.

Association between PM2.5 exposure and the outcomes of ART treatment: A prospective birth cohort study.

Exposure to fine particulate matter (PM2.5) has been reported to be adversely associated with reproductive health. However, current evidence on PM2.5 exposure adversely influencing pregnancy outcomes remains inconclusive. Women receiving assisted reproductive technology (ART) treatment are under close monitoring with regards to their treatment process, which make them great study population to assess the impact of PM2.5 in the post-implantation period. Therefore, within a prospective cohort study in Jiangsu, China, we assessed the associations between exposure to ambient PM2.5 and the outcomes of ART treatment, including implantation failure, biochemical pregnancy loss, clinical pregnancy and live birth, in 2431 women who underwent the first fresh embryo transfer or frozen embryo transfer cycle. High-performance machine-learning model was performed to estimate daily PM2.5 exposure concentrations at 1 km spatial revolution. Exposure windows were divided into seven periods according to the process of follicular and embryonic development in ART. Generalized estimation equations (GEE) was used to assess the association between PM2.5 and ART outcomes. Higher PM2.5 exposure was associated with decreased probability of clinical pregnancy (RR: 0.98, 95 % CI: 0.96-1.00). Each 10 µg/m3 increase in PM2.5 exposure in the duration from hCG test to 30 days after embryo transfer (Period 7) was positively associated with the risk of biochemical pregnancy loss (RR: 1.06, 95 % CI: 1.00-1.13), and more prominent effects were observed in women undergoing fresh embryo transfer. Null associations were observed between PM2.5 exposure and implantation failure or live birth at any exposure window. Collectively, our study suggested that exposure to PM2.5 increased the risk of adverse treatment outcomes in the ART population. Thus, for women opting for ART treatment, particularly those who select fresh embryo transfer cycles, additional evaluation of PM2.5 exposure before treatment might be of value in decreasing the risk of adverse pregnancy outcomes.

Association between prenatal exposure to trace elements mixture and visual acuity in infants: A prospective birth cohort study.

BACKGROUND: Prenatal environmental factors may affect the development of the offspring and can bring long lasting consequences to the offspring's health. To date, only few studies have reported inconclusive association between prenatal single trace element exposure and visual acuity, and no studies have investigated the association between prenatal exposure to trace elements mixture and visual acuity in infants. METHODS: In the prospective cohort study, grating acuity in infants (12 ± 1 months) was measured by Teller Acuity Cards II. Concentrations of 20 trace elements in maternal urine samples collected in early-trimester were measured by Inductively Coupled Plasma Mass Spectrometry. Elastic net regression (ENET) was applied to select important trace elements. Nonlinear associations of the trace elements levels with abnormal grating were explored using the restricted cubic spline (RCS) method. The associations between selected individual elements and abnormal grating acuity were further appraised using the logistic regression model. Then Bayesian Kernel Machine Regression (BKMR) was used to estimate the joint effects of mixture and interactions between trace elements combining with NLinteraction. RESULTS: Of 932 mother-infant pairs, 70 infants had abnormal grating acuity. The ENET model produced 8 trace elements with non-zero coefficients, including cadmium, manganese, molybdenum, nickel, rubidium, antimony, tin and titanium. RCS analyses identified no nonlinear associations of the 8 elements with abnormal grating acuity. The single-exposure analyses using logistic regression revealed that prenatal molybdenum exposure possessed a significantly positive association with abnormal grating acuity (odds ratio [OR]: 1.44 per IQR increase, 95% confidence interval [CI]: 1.05, 1.96; P = 0.023), while prenatal nickel exposure presented with a significantly inverse association with abnormal grating acuity (OR: 0.64 per IQR increase, 95% CI: 0.45, 0.89; P = 0.009). Similar effects were also observed in BKMR models. Moreover, the BKMR models and NLinteraction method identified potential interaction between molybdenum and nickel. CONCLUSIONS: We established that prenatal exposure to high concentration of molybdenum and low concentration of nickel was associated with the increased risk of abnormal visual acuity. Potential interaction may exist between molybdenum and nickel on abnormal visual acuity.

Structural and Functional Changes of Brain in Children With Intermittent Exotropia: A Study Combining Multiple MRI Modalities.

BACKGROUND: To investigate structural and functional changes of brain in children with intermittent exotropia (IXT) and their relationship with clinical features. METHODS: Twenty-one IXT patients (mean age 9.38 ± 2.62 years) and 21 age-, gender-, education-, and handedness-matched healthy controls (HCs, mean age 9.52 ± 3.28 years) underwent high-resolution T1 imaging, diffusion tensor imaging (DTI), and resting-state functional MRI (rs-fMRI). The gray and white matter volume analyzed by voxel-based morphometry (VBM) based on T1 imaging, the fractional anisotropy (FA) and mean diffusivity (MD) indices based on DTI, and the amplitude of low frequency fluctuation (ALFF) value based on rs-fMRI were compared between these 2 groups. The correlations between MRI-derived parameters in significant brain regions and various clinical characteristics of IXT were analyzed. RESULTS: Compared with HCs, IXT children showed significantly decreased FA in right precentral gyrus (PRG) and right postcentral gyrus (POG), and significantly decreased ALFF in bilateral calcarine sulcus, bilateral cuneus, left lingual gyrus, and left superior occipital gyrus. The FA value in right PRG and right POG was negatively correlated with disease duration (r = -0.520, P = 0.016), angle of exodeviation at near (r = -0.549, P = 0.010), and angle of exodeviation at distance (r = -0.547, P = 0.010). CONCLUSIONS: IXT children exhibited abnormalities of white matter microstructure and reduced spontaneous neural activities in brain regions involving in oculomotor performance and binocular fusion. Further studies are needed to determine whether these findings are related to the neuropathologic mechanism or downstream changes of IXT.

Evaluation of Maternal Infection During Pregnancy and Childhood Leukemia Among Offspring in Denmark.

Importance: Maternal infection is common during pregnancy and is an important potential cause of fetal genetic and immunological abnormalities. Maternal infection has been reported to be associated with childhood leukemia in previous case-control or small cohort studies. Objective: To evaluate the association of maternal infection during pregnancy with childhood leukemia among offspring in a large study. Design, Setting, and Participants: This population-based cohort study used data from 7 Danish national registries (including the Danish Medical Birth Register, the Danish National Patient Registry, the Danish National Cancer Registry, and others) for all live births in Denmark between 1978 and 2015. Swedish registry data for all live births between 1988 and 2014 were used to validate the findings for the Danish cohort. Data were analyzed from December 2019 to December 2021. Exposures: Maternal infection during pregnancy categorized by anatomic locations identified from the Danish National Patient Registry. Main Outcomes and Measures: The primary outcome was any leukemia; secondary outcomes were acute lymphoid leukemia (ALL) and acute myeloid leukemia (AML). Offspring childhood leukemia was identified in the Danish National Cancer Registry. Associations were first assessed in the whole cohort using Cox proportional hazards regression models, adjusted for potential confounders. A sibling analysis was performed to account for unmeasured familial confounding. Results: This study included 2 222 797 children, 51.3% of whom were boys. During the approximately 27 million person-years of follow-up (mean [SD], 12.0 [4.6] years per person), 1307 children were diagnosed with leukemia (ALL, 1050; AML, 165; or other, 92). Children born to mothers with infection during pregnancy had a 35% increased risk of leukemia (adjusted hazard ratio [HR], 1.35 [95% CI, 1.04-1.77]) compared with offspring of mothers without infection. Maternal genital and urinary tract infections were associated with a 142% and 65% increased risk of childhood leukemia, with HRs of 2.42 (95% CI, 1.50-3.92) and 1.65 (95% CI, 1.15-2.36), respectively. No association was observed for respiratory tract, digestive, or other infections. The sibling analysis showed comparable estimates to the whole-cohort analysis. The association patterns for ALL and AML were similar to that for any leukemia. No association was observed for maternal infection and brain tumors, lymphoma, or other childhood cancers. Conclusions and Relevance: In this cohort study of approximately 2.2 million children, maternal genitourinary tract infection during pregnancy was associated with childhood leukemia among offspring. If confirmed in future studies, our findings may have implications for understanding the etiology and developing preventive measures for childhood leukemia.

Prenatal titanium exposure and child neurodevelopment at 1 year of age: A longitudinal prospective birth cohort study.

Previous animal studies provided the evidence that prenatal titanium exposure can cause neurotoxicity in their offspring, while human data is vacant. Our aim was to identify the associations of prenatal titanium exposure with the child neurodevelopment. Participants in present study were recruited during early pregnancy between 2014 and 2017. Urinary concentrations of titanium at first trimester were determined. We assessed child neurodevelopment using the Chinese version of Gesell Developmental Schedules at first year follow-up. The multivariable linear regressions and the robust modified Poisson regressions were used to estimate the associations of specific gravity corrected urinary titanium concentrations with the child neurodevelopment. In adjusted models, children's developmental quotient scores in the language domain were 2.03 points (95% CI: -3.66, -0.40) lower in the highest tertile of prenatal urinary titanium than in the lowest tertile. Also, children with prenatal urinary titanium in the highest tertile had 1.42 times (95% CI: 1.17, 1.72) increased risk of language development delay compared to those in the lowest tertile. No statistically significant associations were observed between titanium exposure and child development delay in motor, adaptive and social areas. The findings indicated that prenatal higher titanium exposure was associated with impaired language development, suggesting that titanium might act as developmental neurotoxicants.

Inositol 1,4,5-trisphosphate receptor gene variants are related to the risk of breast cancer in a Chinese population.

BACKGROUND: Mammalian inositol 1,4,5-trisphosphate receptor (ITPR) genes encode ubiquitously expressed endoplasmic reticulum Ca2+ channels that have recently been shown to be closely linked to the pathogenesis of several cancers. However, few studies to date have explored associations between ITPR gene family single nucleotide polymorphisms (SNPs) and breast cancer risk. METHODS: In the present case-control study, 12 SNPs in the potential functional regions of the ITPR1, ITPR2, and ITPR3 genes were genotyped using an Illumina Infinium® Beadchip in 2095 Chinese women (1032 cases and 1063 controls). RESULTS: Multivariate logistic regression analyses indicated that a missense SNP in the ITPR3 coding region (rs2229642) was significantly related to breast cancer risk when using an additive model in this study (rs2229642-adjusted odds ratio = 1.40, 95% confidence interval = 1.12-1.74, p = 2.97 × 10-3 ). Expression quantitative trait loci analyses indicated that the SNP rs2229642 was associated with reduced ITPR3 expression levels (p = 3.2 × 10-7 ) and with marked reductions in the expressions of several proximal genes, including BAK1, GRM4, HLA-DOB, and UQCC2 (p = 0.013, 0.018, 3.4 × 10-3 , 3.8 × 10-5 ), suggesting that it may further regulate other genes associated with oncogenic susceptibility. Kaplan-Meier analyses indicated that the patients with higher ITPR3 expression exhibited significantly poorer outcomes compared to the patients with lower expression of this gene (hazard ratio = 1.11, 95% confidence interval = 1-1.23, p = 0.046). CONCLUSIONS: The results indicated that genetic variant in the coding region of ITPR3 gene may regulate the expressions of its host and some other cancer-related genes, as well as act as potential predictive biomarker for susceptibility to breast cancer in the Chinese population.