Trimester-specific effect of maternal co-exposure to organophosphate esters and phthalates on preschooler cognitive development: The moderating role of gestational vitamin D status.

Organophosphate esters (OPEs) and phthalate acid esters (PAEs) are prevalent endocrine-disrupting chemicals (EDCs). Humans are often exposed to OPEs and PAEs simultaneously through multiple routes. Given that fetal stage is a critical period for neurodevelopment, it is necessary to know whether gestational co-exposure to OPEs and PAEs affects fetal neurodevelopment. However, accessible epidemiological studies are limited. The present study included 2, 120 pregnant women from the Ma'anshan Birth Cohort (MABC) study. The concentrations of tris (2-chloroethyl) phosphate (TCEP), 6 OPE metabolites and 7 PAE metabolites were measured in the first, second and third trimester using ultra-performance liquid chromatography-tandem mass spectrometry (LC-MS). Cognitive development of preschooler was assessed based on the Wechsler Preschool and Primary Scale of Intelligence-Fourth Edition (WPPSI-IV) of the Chinese version. Generalized estimating equations (GEEs), restricted cubic spline (RCS) and generalized additive models (GAMs) were employed to explore the associations between individual OPE exposure and preschooler cognitive development. The quantile-based g-computation (QGC) method was used to estimate the joint effect of PAEs and OPEs exposure on cognitive development. GEEs revealed significant adverse associations between diphenyl phosphate (DPHP) (ß: -0.58, 95% CI: -1.14, -0.01), bis (2-butoxyethyl) phosphate(BBOEP) (ß: -0.44, 95% CI: -0.85, -0.02), bis(1-chloro-2-propyl) phosphate (BCIPP) (ß: -0.81, 95%CI: -1.43, -0.20) and full-scale intelligence quotient (FSIQ) in the first trimester; additionally, TCEP and bis(2-ethylhexyl) phosphate (BEHP) in the second trimester, as well as DPHP in the third trimester, were negatively associated with cognitive development. Through the QGC analyses, mixture exposure in the first trimester was negatively associated with FSIQ scores (ß: -1.70, 95% CI: -3.06, -0.34), mono-butyl phthalate (MBP), BCIPP, and DPHP might be the dominant contributors after controlling for other OPEs and PAEs congeners. Additionally, the effect of OPEs and PAEs mixture on cognitive development might be driven by vitamin D deficiency.

Impact of Gestational Exposure to Individual and Combined Per- and Polyfluoroalkyl Substances on a Placental Structure and Efficiency: Findings from the Ma'anshan Birth Cohort.

Prenatal exposure to perfluoroalkyl and polyfluoroalkyl substances (PFASs) is inevitable among pregnant women. Nevertheless, there is a scarcity of research investigating the connections between prenatal PFAS exposure and the placental structure and efficiency. Based on 712 maternal-fetal dyads in the Ma'anshan Birth Cohort, we analyzed associations between individual and mixed PFAS exposure and placental measures. We repeatedly measured 12 PFAS in the maternal serum during pregnancy. Placental weight, scaling exponent, chorionic disc area, and disc eccentricity were used as the outcome variables. Upon adjusting for confounders and implementing corrections for multiple comparisons, we identified positive associations between branched perfluorohexane sulfonate (br-PFHxS) and 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA) with placental weight. Additionally, a positive association was observed between br-PFHxS and the scaling exponent, where a higher scaling exponent signified reduced placental efficiency. Based on neonatal sex stratification, female infants were found to be more susceptible to the adverse effects of PFAS exposure. Mixed exposure modeling revealed that mixed PFAS exposure was positively associated with placental weight and scaling exponent, particularly during the second and third trimesters. Furthermore, br-PFHxS and 6:2 Cl-PFESA played major roles in the placental measures. This study provides the first epidemiological evidence of the relationship between prenatal PFAS exposure and placental measures.

A hybrid effectiveness-implementation trial of application-based tiered care (Mom's Good Mood) in treating perinatal anxiety within a primary health care system in China.

INTRODUCTION: Perinatal anxiety (PNA) is a major public health concern. METHODS: A hybrid effectiveness-implementation trial was conducted in two antenatal clinics in Hefei, China, to assess the effectiveness and cost-effectiveness of application-based tiered care (Mom's Good Mood, MGM) in treating PNA and to understand how well it fits into routine practices. Pregnant women who scored at least 5 points on the 7-Item Generalised Anxiety Disorder Scale (GAD-7) scale were successively assigned to the control group or the intervention group, which were given the usual care and MGM on usual care, respectively. At 6 months post partum, anxiety, depression and life satisfaction were assessed. Intention-to-treat analysis and the Reach, Effectiveness, Adoption, Implementation and Maintenance framework were adopted. RESULTS: A total of 214 women were assigned to the control group and 341 to the intervention group. The mean changes in GAD-7 scores (Least-squares means, LSM, -1.42, 95% CI -2.18 to -0.66) and the risk of anxiety (adjusted odds ratio, aOR 0.30, 95% CI 0.18 to 0.51) were decreased, and the anxiety remission rate (aOR 2.72, 95% CI 1.69 to 4.40) were improved in the intervention group. Similar findings were observed regarding the change in Edinburgh Postnatal Depression Scale scores (LS -1.92, 95% CI -2.85 to -0.99), depression remission rate (aOR 2.24, 95% CI 1.39 to 3.63) and the risk of depression (aOR 0.57, 95% CI 0.33 to 0.98). MGM only costs ¥1.88 (US$0.27) per pregnant woman to boost the postpartum anxiety remission rate by 1% and was revealed to have a high reach rate of 78.3%, an adoption rate of 51.3%-80.8%. CONCLUSION: MGM is a cost-effective and accessible tool in coping with PNA. TRIAL REGISTRATION NUMBER: ChiCTR2100053419.

Associating phthalate exposure during pregnancy with preschooler's FMI, ABSI and BRI trajectories via putative mechanism pathways.

Phthalates are well-known obesogens, but a few studies have explored their impacts on the childhood fat mass index (FMI), body shape index (ABSI) and body roundness index (BRI). Information from 2950 participants recruited in the Ma'anshan Birth Cohort was analyzed. The relationships between six maternal phthalate metabolites and their mixture and childhood FMI, ABSI and BRI were investigated. FMI, ABSI and BRI in children aged 3.5 y, 4.0 y, 4.5 y, 5.0 y, 5.5 y and 6.0 y were calculated. The latent class trajectory modeling categorized the FMI trajectories into "rapidly increasing FMI" (4.71%) and "stable FMI" (95.29%) groups; ABSI trajectories were categorized as "decreasing ABSI" (32.74%), "stable ABSI" (46.55%), "slowly increasing ABSI" (13.26%), "moderately increasing ABSI" (5.27%) and "rapidly increasing ABSI" (2.18%) groups; BRI trajectories were categorized as "increasing BRI" (2.82%), "stable BRI" (19.85%), and "decreasing BRI" (77.34%) groups. Prenatal MEP exposure was associated with repeated measurements of FMI (ß = 0.111, 95% CI = 0.002-0.221), ABSI (ß = 0.145, 95% CI = 0.023-0.268) and BRI (ß = 0.046, 95% CI = -0.005-0.097). Compared with each stable trajectory group, prenatal MEP (OR = 0.650, 95% CI = 0.502-0.844) and MBP (OR = 0.717, 95% CI = 0.984-1.015) were linked to a decreased risk of "decreasing BRI" in children; there was a negative relationship between MBP and the "decreasing ABSI" group (OR = 0.667, 95% CI = 0.487-0.914), and MEP increased the risks of "slowly increasing ABSI" (OR = 1.668, 95% CI = 1.210-2.299) and "rapidly increasing ABSI" (OR = 2.522, 95% CI = 1.266-5.024) in children. Phthalate mixture during pregnancy showed significant relationships with all anthropometric indicator trajectories, with MEP and MBP always being of the largest importance. In conclusion, this study suggested that prenatal phthalate coexposure increased the childhood probability of being in higher ABSI and BRI trajectory groups. That is, children were more likely to be obese when they were exposed to higher levels of some phthalate metabolites and their mixture. The low-molecular weight phthalates, including MEP and MBP, contributed the greatest weights.

Mom's Good Mood: screening and management of perinatal depression within primary healthcare system in China-protocol for an effectiveness-implementation design study.

INTRODUCTION: The management of perinatal depression (PND) is challenging in China. The Thinking Healthy Programme (THP), developed under the core theory of cognitive-behavioural therapy, is an evidence-based approach that is recommended as a psychosocial intervention for managing PND in low/middle-income countries. Sparse evidence has been generated, however, to assess the effectiveness of THP and guide its implementation in China. METHODS AND ANALYSIS: A hybrid type II effectiveness-implementation study is ongoing in four cities in Anhui Province, China. A comprehensive online platform, Mom's Good Mood (MGM), has been developed. Perinatal women are screened using the WeChat screening tool (ie, Edinburgh Postnatal Depression Scale embedded as metrics) in clinics. Different intensities of the intervention are delivered through the mobile application for different degrees of depression, according to the stratified care model. The THP WHO treatment manual has been tailored to be the core component of intervention. Guided by the Reach, Effectiveness, Adoption, Implementation and Maintenance framework, process evaluations will be conducted to identify the facilitators and barriers to implementation and to modify the implementation strategy; summative evaluations will be carried out to examine the effectiveness of MGM in the management of PND within the primary healthcare system in China. ETHICS AND DISSEMINATION: Ethics approval and consent for this programme were obtained from Institutional Review Boards in China: Anhui Medical University, Hefei, People's Republic of China (20170358). Results will be submitted to relevant conferences and peer-reviewed journals. TRIAL REGISTRATION NUMBER: ChiCTR1800016844.

Joint effects of recent stressful life events and adverse childhood experiences on perinatal comorbid anxiety and depression.

BACKGROUND: Stressful life events (SLEs) and adverse childhood experiences (ACEs) have been reported to be associated with perinatal depression (PND) or perinatal anxiety (PNA) alone; however, in most cases, majority of PND and PNA coexist and could lead to more serious health consequences. The independent effect of recent SLEs and their joint effects with ACEs on perinatal comorbid anxiety and depression (CAD) remain inadequately explored. METHODS: Based on a longitudinal study, 1082 participants receiving prenatal care in Ma'anshan, China were included. Women were recruited in the first trimester (T1: ≤14+ 6 weeks) and followed up at 15 ~ 27 weeks (T2), 28 ~ 40 weeks (T3), and postpartum (T4). Depression and anxiety status were assessed at all time points, while recent SLEs and ACEs were measured at T1. Logistic regression was conducted to examine the associations of SLEs with the risks of CAD at different time points, as well as their joint effects with ACEs on CAD. RESULTS: Approximately 38.5% of women experienced at least one SLE, which was significantly associated with higher risks of CAD at all time points (p < 0.05). As the number of SLEs increased, the risk of CAD increased (p for trend < 0.05). Specific types of SLEs were associated with CAD in different periods, while only interpersonal events were consistently associated with risks of CAD throughout the whole perinatal period. The joint effects of SLEs with ACEs on CAD were identified throughout the perinatal period, with the highest observed in the first trimester (aOR = 7.47, 95% CI: 3.73-14.95; p for trend < 0.001). CONCLUSION: Our study demonstrated independent associations of recent SLEs and their joint effects with ACEs with risks of perinatal CAD. SLEs combined with ACEs should be recognized as a major risk factor for perinatal CAD and managed at the earliest time to prevent and control CAD.

A systematic scoping review of epidemiological studies on the association between organophosphate flame retardants and neurotoxicity.

Organophosphate flame retardants (OPFRs) are increasingly and widely used as substitutes for brominated flame retardants in daily life. The chemical structure of OPFRs is very similar to that of organophosphorus pesticides, leading to concerns about their neurotoxicity. A few epidemiological studies have been published with inconsistent results on this topic, and a systematic scoping review is needed to provide an overview or map of the current evidence on the relationship of OPFRs with neurodevelopmental toxicity. Therefore, MEDLINE (accessed through PubMed), Web of Science, and CNKI (Chinese National Knowledge Infrastructure) were systematically searched for articles published in the last two decades. Nine eligible articles were included in the present systematic scoping review for adherence to the predefined PECOS (population, exposure, comparison, outcome, study design) statement. Six studies were conducted in the USA, and the remaining three studies were conducted in Austria, Norway and China. A total of 2 581 children (1 203 females and 1 378 males) were included. Half of the included studies focused on the adverse effects of OPFR exposure on cognition in children, while others primarily focused on the behaviors of children. In summary, the current evidence suggests inverse associations between early-life exposure to OPFRs and the childhood intelligence quotient and internalizing behavior and positive relationships of OPFR exposure with externalizing behavior. However, some differences in the timing of sample collection for exposure measurements, in the individual OPFR metabolites available, in the neurodevelopmental scales for outcome measurement, and in the statistical methods used to analyze the data are noted. In addition, further studies are warranted to evaluate some important issues, such as sex differences in the association, exposure-sensitive periods, and cumulative exposure risk assessment.

A longitudinal cohort study of gestational diabetes mellitus and perinatal depression.

BACKGROUND: The association between gestational diabetes mellitus (GDM) and perinatal depression (PND) remains controversial. Our study aimed to comprehensively assess this association in a longitudinal cohort study with repeated measurements of depression. METHODS: Our cohort study was nested in a pilot study of an implementation study aiming to screen and manage perinatal depression within the primary health system in China. Women were recruited in the first trimester from May-September 2019 and followed four times up to 1 year postpartum. Data on sociodemographic characteristics and depression were collected using self-developed questionnaires incorporating the Edinburgh Postnatal Depression Scale (EPDS). Oral glucose tolerance test at 24 ~ 28 weeks and fasting plasma glucose (FPG) data were extracted from medical records. Depression throughout the whole period was divided into different trajectories. Associations of GDM with PND at different time periods and PND of different trajectories were determined by logistic regression. The path of association between blood glucose and depression over time was estimated with an autoregressive cross-lagged model. RESULTS: In total, 1043 women were included in this analysis and 313 (30.0%) were diagnosed with GDM. The prevalence of depression in the first, second, and third trimesters and postpartum period were 17.2, 6.9, 6.8 and 9.0%, respectively. GDM was neither significantly associated with PND at any time point nor with any specific trajectory of depression. Except for autoregressive paths, no cross-lagged path of FPG and scores of EPDS was significant. CONCLUSIONS: Our study indicates no association between GDM/blood glucose and PND.

What stakeholders think: perceptions of perinatal depression and screening in China's primary care system.

BACKGROUND: Mental health in China is a significant issue, and perinatal depression has been recognized as a concern, as it may affect pregnancy outcomes. There are growing calls to address China's mental health system capacity issues, especially among vulnerable groups such as pregnant women due to gaps in healthcare services and inadequate access to resources and support. In response to these demands, a perinatal depression screening and management (PDSM) program was proposed. This exploratory case study identified strategies for successful implementation of the proposed PDSM intervention, informed by the Consolidated Framework for Implementation Research (CFIR) framework, in Ma'anshan city, Anhui province. METHODS: This qualitative study included four focus group discussions and two in-depth individual interviews with participants using a semi-structured interview guide. Topics examined included acceptance, utility, and readiness for a PDSM program. Participants included perinatal women and their families, policymakers, and healthcare providers. Interviews were transcribed verbatim, coded, and analyzed for emergent themes. RESULTS: The analysis revealed several promising factors for the implementation of the PDSM program including: utilization of an internet-based platform, generation of perceived value among health leadership and decision-makers, and the simplification of the screening and intervention components. Acceptance of the pre-implementation plan was dependent on issues such as the timing and frequency of screening, ensuring high standards of quality of care, and consideration of cultural values in the intervention design. Potential challenges included perceived barriers to the implementation plan among stakeholders, a lack of trained human health resources, and poor integration between maternal and mental health services. In addition, participants expressed concern that perinatal women might not value the PDSM program due to stigma and limited understanding of maternal mental health issues. CONCLUSION: Our analysis suggests several factors to support the successful implementation of a perinatal depression screening program, guidelines for successful uptake, and the potential use of internet-based cognitive behavioral therapy. PDSM is a complex process; however, it can be successfully navigated with evidence-informed approaches to the issues presented to ensure that the PDSM is feasible, effective, successful, and sustainable, and that it also improves maternal health and wellbeing, and that of their families.