Protein Bait Hypothesis: circRNA-Encoded Proteins Competitively Inhibit Cognate Functional Isoforms.

Recent studies have demonstrated that a large group of proteins encoded by circular RNAs (circRNAs) are likely to play a role in cancer development; however, there remains a substantial gap in our understanding of this group of proteins and their functional mechanisms involved. Therefore, we propose the protein bait hypothesis, which specifies that circRNA-encoded proteins compete with their cognate linearly spliced protein isoforms for binding molecules, preventing proper isoform functioning. This hypothesis may expand our understanding of the functional mechanisms of circRNA-encoded proteins and prove useful in elucidating the mechanisms underlying human development, physiology, and diseases, and in parallel, also aid in drug discovery.

Impact of levothyroxine therapy for maternal subclinical and overt hypothyroidism on early child neurodevelopment: A prospective cohort study.

OBJECTIVE: Treatment indication of maternal subclinical hypothyroidism (SCH) is undetermined, despite the wide administration of levothyroxine for maternal overt hypothyroidism (OH). This study aimed to evaluate the therapeutic effect of levothyroxine for maternal SCH and OH in real-world practice, with a focus on early child neurodevelopment. DESIGN: Prospective cohort study. PATIENTS AND MEASUREMENTS: Pregnant women diagnosed with SCH at the first antenatal visit were enroled and compared to those diagnosed with OH. Thyroid follow-ups were conducted during pregnancy. Early child neurodevelopment was assessed using the Gesell Development Diagnosis Scale (GDDS) at 1, 3, 6, 12 and 24 months of age. RESULTS: From January 2012 to December 2013, a total of 442 pregnant women were included in final analysis, among whom 194 and 248 were assigned to the SCH and OH groups, respectively. The percentage of levothyroxine therapy at the first antenatal visit was significantly lower in the SCH group than that in the OH group (91.24% vs. 97.58%, p < .01), with a similar treatment rate at delivery (99.4% vs. 100%, p > .05). Notably, GDDS scores were lower in the SCH group than those in the OH group at 6 months to 2 years of age, which was confirmed by subgroup analyses and sensitivity analyses. CONCLUSIONS: Children born with maternal SCH demonstrated slightly lower neuropsychological scores at 6 months to 2 years of age compared to those with maternal OH in the clinical practice. The therapeutic effect of maternal SCH on the child neurodevelopment requires further exploration.

Preconception folic acid supplementation for the prevention of birth defects: a prospective, population-based cohort study in mainland China.

BACKGROUND: Folic acid supplementation is recommended for reducing the risk of birth defects. We aimed to assess the protective association of periconception folic acid supplements with birth defects in real-world setting. METHODS: This prospective, population-based cohort study utilized national preconception registered data of married Chinese couples planning a pregnancy within 6 months between 2010 and 2012 in Mainland China. Participated women are freely provided folic acid starting 3 months before conception till 3 months after conception. Birth defects were self-reported at 42 days postpartumn followup. R software (v4.0.2) was applied for statistical analyses. RESULTS: Complete data of 567,547 couples with pregnancy outcomes and folic acid supplementation were extracted for final analysis. A total of 74.7% women were with folic acid supplementation, and 599 birth defects were self-reported. The odd of birth defects was lower among women taking folic acid compared to their counterparts not taking (0.102% vs 0.116%, P < 0.001). In the multiple logistic regression analyses, the odd of birth defects was lower among couples with maternal folic acid supplementation (OR = 0.78, 95%CI: 0.66-0.95, P = 0.011), especially decreased odd of neural tube defects (NTDs) (OR = 0.56, 95%CI: 0.39-0.82, P = 0.003). This association was confirmed by 1:4 and 1:10 case control analysis. Odds of birth defects were significantly lower among women with folic acid supplementation more than 3 months before pregnancy (P < 0.001), and moreover, the odds of cleft (P = 0.007) and NTDs (P = 0.007) were of notable decrease. CONCLUSION: This retrospective case cohort study provides programmatic evidence for public health strategy-making to for reducing the risk of NTDs and clefts.

Association between twin status with cognitive, behavioral development and brain structure in early adolescence: a retrospective cohort analysis based on the Adolescent Brain Cognitive Development Study.

Twin births are related with maternal and fetal adverse outcomes. Little was known about the comparability of the cognitive, behavioral development and brain structure between twins and singletons in early adolescence. This retrospective cohort study was based on data from the United States population-based, prospective, longitudinal observational Adolescent Brain Cognitive Development study. Children with complete twin status information were enrolled, and the exposure variable was twin status. Primary outcomes were cognitive, behavioral development and brain structure in early adolescence. Cognitive and behavioral outcomes were assessed by using the NIH Toolbox and Child Behavioral Checklist, respectively. Brain structure was evaluated by the cortical thickness, area, and volume extracted from the magnetic resonance imaging (MRI) data. Subgroup analyses were conducted by prematurity, birth weight, with sibling, genetic profiles, and twin types (zygosity). From 1st September 2016 to 15th November 2018, 11545 children (9477 singletons and 2068 twins) aged 9-10 years were enrolled. Twins showed mildly lower cognitive performance (|t|> 5.104, P-values < 0.001, False Discovery Rate [FDR] < 0.001), better behavioral outcome (|t|> 2.441, P-values < 0.015, FDR < 0.042), such as lower scores for multiple psychiatric disorders and behavioral issues, and smaller cortical volume (t = - 3.854, P-values < 0.001, FDR < 0.001) and cortical area (t = - 3.872, P-values < 0.001, FDR < 0.001). The observed differences still held when stratified for prematurity, birth weight, presence of siblings, genetic profiles, and twin types (zygosity). Furthermore, analyses on the two-year follow-up data showed consistent results with baseline data. Twin status is associated with lower cognitive and better behavioral development in early adolescence accompanied by altered brain structure. Clinicians should be aware of the possible difference when generalizing results from adolescent twin samples to singletons.

Environmental Enrichment Protects Offspring of a Rat Model of Preeclampsia from Cognitive Decline.

Preeclampsia affects 5-7% of all pregnancies and contributes to adverse pregnancy and birth outcomes. In addition to the short-term effects of preeclampsia, preeclampsia can exert long-term adverse effects on offspring. Numerous studies have demonstrated that offspring of preeclamptic women exhibit cognitive deficits from childhood to old age. However, effective ways to improve the cognitive abilities of these offspring remain to be investigated. The aim of this study was to explore whether environmental enrichment in early life could restore the cognitive ability of the offspring of a rat model of preeclampsia and to investigate the cellular and molecular mechanisms by which EE improves cognitive ability. L-NAME was used to establish a rat model of preeclampsia. The spatial learning and memory abilities and recognition memory of 56-day-old offspring were evaluated by the Morris water maze and Novel object recognition (NOR) task. Immunofluorescence was performed to evaluate cell proliferation and apoptosis in the DG region of the hippocampus. qRT-PCR was performed to examine the expression levels of neurogenesis-associated genes, pre- and postsynaptic proteins and inflammatory cytokines. An enzyme-linked immune absorbent assay was performed to evaluate the concentration of vascular endothelial growth factor (VEGF) and inflammatory cytokines in the hippocampus. The administration of L-NAME led to increased systolic blood pressure and urine protein levels in pregnant rats. Offspring in the L-NAME group exhibited impaired spatial learning ability and memory as well as NOR memory. Hippocampal neurogenesis and synaptic plasticity were impaired in offspring from the L-NAME group. Furthermore, cell apoptosis in the hippocampus was increased in the L-NAME group. The hippocampus was skewed to a proinflammatory profile, as shown by increased inflammatory cytokine levels. EE improved the cognitive ability of offspring in the L-NAME group and resulted in increased hippocampal neurogenesis and synaptic protein expression levels and decreased apoptosis and inflammatory cytokine levels. Environmental enrichment resolves cognitive impairment in the offspring of a rat model of preeclampsia by improving hippocampal neurogenesis and synaptic plasticity and normalizing the apoptosis level and the inflammatory balance.

Association between levothyroxine treatment for maternal subclinical hypothyroidism with negative TPOAb and early child neurodevelopment: A prospective real-world clinical trial.

INTRODUCTION: Subclinical hypothyroidism (SCH) during pregnancy is reported to have detrimental impact on pregnancy and child development. However, its treatment indications require further investigation in different thyroid peroxidase antibody (TPOAb) status. MATERIAL AND METHODS: This was a secondary analysis of a Chinese prospective cohort in a real-world setting. Pregnant women with gestational SCH were enrolled at the first antenatal visit and grouped by TPOAb positivity. Child neurodevelopment was assessed by the Gesell development diagnosis scale (GDDS) at one, three, six, 12, and 24 months of age. Subgroup analyses and sensitivity analyses were also conducted. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT01744743. RESULTS: From January 2012 to December 2013, a total of 171 participants were enrolled, including 116 of SCH with TPOAb negative (SCH-TPOAb [-]) and 55 of SCH with TPOAb positive (SCH-TPOAb [+]). Compared to women in the SCH-TPOAb (+) group, those in the SCH-TPOAb (-) group had lower thyroid-stimulating hormone (TSH) levels at enrollment and 12-16+6 gestational weeks, and unexpectedly higher TSH levels at 30-34+6 gestational weeks and delivery, with a correspondingly lower levothyroxine dosage throughout pregnancy (all p < 0.05). Offspring in the SCH-TPOAb (-) group displayed lower GDDS scores at one year old than did their counterparts (adjusted p < 0.05), which was possibly related to the worse thyroid function control of maternal SCH-TPOAb (-). No statistically significant difference was found in the GDDS assessments of children at one, three, six, and 24 months of age. These results were also confirmed in subgroup analyses stratified by maternal thyroid characteristics at enrollment, namely TSH levels, free levothyroxine (T4 ) levels, and anti-thyroglobulin antibody (TgAb) status, as well as in sensitivity analyses excluding participants with no levothyroxine treatment at enrollment. CONCLUSIONS: In the current clinical practice, infants born to mothers with SCH-TPOAb (-) displayed slightly lower neurodevelopmental scores at one year old than did those born to mothers with SCH-TPOAb (+) but this difference was not seen at two years.

Association of maternal hypertension during pregnancy with brain structure and behavioral problems in early adolescence.

Emerging evidence suggests an association between maternal hypertension during pregnancy and mental health in the offspring. However, less is known about the role of hypertensive pregnancy in behavioral symptoms and brain structures of the offspring as well as in their developmental changes. Here, we utilized neuroimaging and behavioral data from 11,878 participants aged 9-10 years and their 2-year follow-up from the Adolescent Brain Cognitive Development (ABCD) study to investigate the long-term effects of maternal hypertension during pregnancy on early adolescent behavior and brain anatomy. Specifically, adolescents born of mothers with maternal hypertension are at risk of long-lasting behavioral problems, as manifested by higher externalizing and internalizing behavior scores at both 9-10 years and 11-12 years. These participants additionally presented with a higher cortical thickness, particularly in the fronto-parieto-temporal areas at 9-10 years. Four regions, including the left parahippocampus, left lateral orbitofrontal lobe, right superior temporal lobe and right temporal pole, remained thicker 2 years later. These findings were partially validated in rats modeled with Nω-nitro-L-arginine methyl ester (L-NAME) preeclampsia. Therefore, clinicians and women who experience hypertension during pregnancy should be warned of this risk, and healthcare providers should recommend appropriate clinical interventions for pregnancy-induced hypertension.

Lower gestational age is associated with lower cortical volume and cognitive and educational performance in adolescence.

BACKGROUND: Gestational age (GA) is associated with later cognition and behavior. However, it is unclear how specific cognitive domains and brain structural development varies with the stepwise change of gestational duration. METHODS: This large-scale longitudinal cohort study analyzed 11,878 early adolescents' brain volume maps at 9-10 years (baseline) and 5685 at 11-12 years (a 2-year follow-up) from the Adolescent Brain Cognitive Development (ABCD) study. According to gestational age, adolescents were divided into five categorical groups: ≤ 33 weeks, 34-35 weeks, 36 weeks, 37-39 weeks, and ≥ 40 weeks. The NIH Toolbox was used to estimate neurocognitive performance, including crystallized and fluid intelligence, which was measured for 11,878 adolescents at baseline with crystallized intelligence and relevant subscales obtained at 2-year follow-up (with participant numbers ranging from 6185 to 6310 depending on the cognitive domain). An additional large population-based cohort of 618,070 middle adolescents at ninth-grade (15-16 years) from the Danish national register was utilized to validate the association between gestational age and academic achievements. A linear mixed model was used to examine the group differences between gestational age and neurocognitive performance, school achievements, and grey matter volume. A mediation analysis was performed to examine whether brain structural volumes mediated the association between GA and neurocognition, followed with a longitudinal analysis to track the changes. RESULTS: Significant group differences were found in all neurocognitive scores, school achievements, and twenty-five cortical regional volumes (P < 0.05, Bonferroni corrected). Specifically, lower gestational ages were associated with graded lower cognition and school achievements and with smaller brain volumes of the fronto-parieto-temporal, fusiform, cingulate, insula, postcentral, hippocampal, thalamic, and pallidal regions. These lower brain volumes mediated the association between gestational age and cognitive function (P = 1 × 10-8, ß = 0.017, 95% CI: 0.007-0.028). Longitudinal analysis showed that compared to full term adolescents, preterm adolescents still had smaller brain volumes and crystallized intelligence scores at 11-12 years. CONCLUSIONS: These results emphasize the relationships between gestational age at birth and adolescents' lower brain volume, and lower cognitive and educational performance, measured many years later when 9-10 and 11-12 years old. The study indicates the importance of early screening and close follow-up for neurocognitive and behavioral development for children and adolescents born with gestational ages that are even a little lower than full term.

Preeclampsia risk prediction model for Chinese pregnant women (ChiPERM): research protocol for a randomized stepped-wedge cluster trial.

BACKGROUND: Despite international clinical guideline recommendations, implementation of Bayes-theorem based preeclampsia risk prediction model in first trimester among Chinese women is limited. The aim of this study is to examine the effectiveness of this risk predictive strategy in reducing the risk of preeclampsia. METHODS: The study will be a randomized, stepped-wedge controlled trial conducted in eighteen hospitals in China. Stepped implementation of Bayes-theorem based risk prediction model will be delivered to hospitals in a random order to support the introduction of this prediction model of preeclampsia. A staged process will be undertaken to develop the risk prediction strategies, which comprise of: combined risk evaluation by maternal risk factors, medium arterial pressure, uterine artery pulse index and placenta growth factor during 11-13+6 gestational weeks, monthly follow up (including blood pressure, newly onset complications, adherence to aspirin). Repeated cross-sectional outcome data will be gathered weekly across all hospitals for the study duration. The primary outcome measures are the incidence of preeclampsia within 42 days postpartum. Data on resources expended during intervention development and implementation will be collected. The incidence of pregnancy related complications will be measured as secondary outcomes. DISCUSSION: This will be the first randomized controlled trial to evaluate the effectiveness of the Bayes-theorem based preeclampsia risk prediction strategies in first trimester by competing risk model validation. If positive changes in clinical practice are found, this evidence will support health service adoption of this risk prediction model to reduce the risk of preeclampsia among Chinese pregnant women. TRIAL REGISTRATION: Chinese Clinical Trials Registry, No. ChiCTR2100043520 (date registered:21/2/2021).

Perfluorooctane sulfonate exposure induces preeclampsia-like syndromes by damaging trophoblast mitochondria in pregnant mice.

Preeclampsia, defined as a hypertensive disorder during pregnancy, is a major cause of maternal and fetal mortality. Observational studies have shown that the exposure of per- and polyfluoroalkyl substances, such as perfluorooctane sulfonate (PFOS), is emerging as a significant environmental factor associated with preeclampsia risk. However, epidemiologic evidence is of correlative in nature, and unable to establish a causal relationship. Here, we established an animal model of PFOS-induced preeclampsia to explore the molecular mechanism of PFOS in placental trophoblast. In the mouse model, PFOS exposure by gavage at a dose of 10 mg/kg/d from embryonic day 7.5-16.5 was sufficient to induce preeclampsia-like symptoms such as hypertension, proteinuria, and renal glomerular endotheliosis, accompanied with placental abnormal stromal collagen deposition. In-vitro experiments of JEG-3 cells, PFOS exposure impaired trophoblast motility including the compromised abilities of migration, invasion and vascularization. Mechanistically, these pathological effects on cells resulted from SLC25A5-mediated mitochondrial damages, characterized by excessive ROS generation, decreased ATP production and mitochondrial membrane potential loss, and accompanied by the activation of p38 MAPK and JNK signaling pathways. This pioneering study provided biological plausibility to the causality verified by the animal model and the in vitro experiments, which indicates that PFOS exposure may cause preeclampsia during pregnancy via impairing trophoblast mitochondria.

[Latest Findings on Prediction and Prevention of Preeclampsia].

Preeclampsia, a progressive disease involving multiple systems, afflicts pregnancy specifically. It contributes to severe maternal and perinatal morbidity and mortality. It has been reported that preeclampsia initiates from a mismatch between the utero-placental supply and demand, which subsequently triggers the release of placental syncytiotrophoblast stress-derived factors and an imbalance of proangiogenic/antiangiogenic factors, eventually causing maternal systemic endothelial lesions and systemic inflammatory response. Currently, treatments available for preeclampsia are very limited in number. Hence, prediction and prevention carry special significance. Herein, we reviewed the current understanding of preeclampsia, especially findings on the prediction and prevention of preeclampsia published within the past 5 years. We discussed the Fetal Medicine Foundation (FMF) screening model based on placental growth factor (PlGF) and the effects of aspirin, calcium, exercise, and termination of pregnancy in preventing preeclampsia. The efficacy and safety of other new preventive measures still need further validation.

LSD2/KDM1B and its cofactor NPAC/GLYR1 endow a structural and molecular model for regulation of H3K4 demethylation.

Dynamic regulation of histone methylation represents a fundamental epigenetic mechanism underlying eukaryotic gene regulation, yet little is known about how the catalytic activities of histone demethylases are regulated. Here, we identify and characterize NPAC/GLYR1 as an LSD2/KDM1b-specific cofactor that stimulates H3K4me1 and H3K4me2 demethylation. We determine the crystal structures of LSD2 alone and LSD2 in complex with the NPAC linker region in the absence or presence of histone H3 peptide, at resolutions of 2.9, 2.0, and 2.25 Å, respectively. These crystal structures and further biochemical characterization define a dodecapeptide of NPAC (residues 214-225) as the minimal functional unit for its cofactor activity and provide structural determinants and a molecular mechanism underlying the intrinsic cofactor activity of NPAC in stimulating LSD2-catalyzed H3K4 demethylation. Thus, these findings establish a model for how a cofactor directly regulates histone demethylation and will have a significant impact on our understanding of catalytic-activity-based epigenetic regulation.

Missed opportunities for venous thromboembolism prophylaxis during pregnancy and the postpartum period: evidence from mainland China in 2019.

BACKGROUND: Venous thromboembolism (VTE) has become one of the leading causes of maternal mortality. Thromboprophylaxis is recommended for the prevention of this condition; however, its use appears to be insufficient. Therefore, in this study, we aimed to identify the missed opportunities for VTE prophylaxis in hospitals that provide maternal healthcare in mainland China. METHODS: In this cross-sectional survey-based study, we collected case data on pregnant and puerperal women with deep vein thrombosis and pulmonary thromboembolism from January 1st to December 31st, 2019. Demographics, obstetric information, VTE risk assessment scores, and prophylaxis-related information were recorded. Thromboprophylaxis included mobilization, mechanical methods, and treatment with anticoagulants. RESULTS: Data corresponding to a total of 106 cases from 26 hospitals across China were collected, and 100 (94.3%) cases, 75 cases involving deep vein thrombosis and 25 cases involving pulmonary thromboembolism, were included in the final analysis. VTE occurred in 80% of the patients at the postpartum stage, while 20 patients developed the disease during the antenatal stage. Cesarean section, advanced maternal age, and obesity were the most common risk factors related to VTE during the postpartum stage, while a previous VTE-related history was a prominent risk factor among antenatal cases. Up to 75% of the patients had one or more missed opportunities for prophylaxis. The lack of the implementation of mechanical methods (60.8% vs. 24.5%, P < 0.001) and anticoagulant treatment (61.1% vs. 48.7%, P < 0.001) were more common in general hospitals compared to those of specialized hospitals. In women assessed as high-risk, anticoagulant treatment was lacking in 41 (54.7%) cases. More importantly, the lack of the implementation of mechanical methods was more common among women assessed as low-risk (56.0% vs. 38.7%, P < 0.001). Among the antenatal cases, the lack of treatment with anticoagulants (100.0% vs. 48.5%, P < 0.001) and implementation of mechanical methods (70.0% vs. 36.7%, P < 0.001) was highlighted. In addition, the lack of early mobilization was much more prominent among the PTE cases (10.5% vs. 37.5%, P < 0.001). CONCLUSIONS: At least one prophylactic opportunity was missed in most of the enrolled Chinese women with VTE during the course of their maternal healthcare. Missed prophylactic opportunities varied with the type of hospitals, risk assessment, onset timing and disease type. Further efforts from patients, healthcare systems, and healthcare providers are needed for improving the implementation of preventative strategies.

Changing trends of adverse pregnancy outcomes with maternal age in primipara with singleton birth: A join point analysis of a multicenter historical cohort study in China in 2011-2012.

INTRODUCTION: Adverse pregnancy outcomes are related to two opposite maternal factors, youth and aging. However, the change in trend of specific outcomes with childbearing age is unknown. The aim of this study was to investigate the changing trend of various maternal and neonatal outcomes with maternal age from 17 to 44 years. MATERIAL AND METHODS: Data were extracted from the medical records from 2011-2012 of 39 public hospitals of 14 cities in China. The eligibility criteria were primiparity and singleton birth. Join point regression analysis was used to estimate the percent change per year of age (PCA) to explore the trends of adverse pregnancy outcomes with regard to maternal age and to identify the join point of maternal age when the trend was changed. RESULTS: A total of 89 171 women were eligible for analysis. There were four categories of trend styles. Continuously increasing trends were linear for placenta previa (PCA, 0.1%), placenta implantation (PCA, 0.09%) and postpartum hemorrhage (PCA, 0.22%), and nonlinear for gestational diabetes mellitus with one join point of 23 years (PCA, 0.17% and 0.71%) and cesarean section with four join points of 25, 28, 31 and 36 years (PCA, 1.39%, 0.34%, 1.51%, 3.49% and 0.94%). Continuously decreasing trends were linear for intrahepatic cholestasis (PCA, -0.02%) and nonlinear for anemia with one join point of 28 years (PCA, -0.49% and -0.04%). The bidirective trends were downward to upward for preterm birth (PCA, -2.93%, -0.36% and 0.38%), hypertension in pregnancy (PCA, -0.09%, 0.47%), low birthweight (PCA 0.51% and 0.38%), low 1-minute Apgar score (PCA, -0.28% and 0.07%), low 5-minute Apgar score at (PCA, -0.10% and 0.06%) and neonatal intensive care unit admission (PCA, -1.92%, -0.07% and 0.12%) with a nadir age of 28 years. The bidirective trend was upward to downward for macrosomia (PCA, 0.39% and -0.11%), with a peak age of 30 years. CONCLUSIONS: The changes in the trend of specific outcomes were different with maternal age, which means that youth, aging or both could affect the outcomes.

The value of ultrasound in predicting isolated inter-twin discordance and adverse perinatal outcomes.

PURPOSE: To investigate the value of ultrasound approaching delivery to predict isolated inter-twin discordance and adverse perinatal outcomes. METHODS: We retrospectively included twin pregnancies with sonography approaching delivery in ten maternal-foetal medicine centres in China from 2013 to 2014. Estimated foetal weight (EFW) and inter-twin EFW disparity (EFWD) were calculated based on biometry parameters. Percentage errors between EFW and actual birthweight or between EFWD and actual inter-twin disparity were calculated. ROC curves and multiple logistic regression were applied to evaluate the ability of EFWD to predict inter-twin disparity ≥ 25%, stillbirth, asphyxia and admission to a neonatal intensive unit (NICU). Chorionicity-stratified analysis was further performed. RESULTS: Two hundred sixty-six monochorionic and 760 dichorionic twin pregnancies were analysed. The percentage errors in foetal weight estimations were 7-13%, whereas percentage errors in the estimation of inter-twin disparity were nearly 100%. Among eight formulas, Hadlock1 performed best, with a detectable rate of 65% and a false positive rate of 5% when predicting inter-twin disparity ≥ 25%. EFWD ≥ 22% was strongly associated with stillbirth (OR = 4.17, 95% CI 1.40-12.40) and NICU admission (OR = 3.48, 95% CI 2.03-5.97) after adjustment for gestational age, parity and abnormal umbilical systolic/diastolic ratio. Ultrasound had better predictive ability in monochorionic twins. CONCLUSION: The predictive value of ultrasound for isolated inter-twin discordance and adverse perinatal outcomes was limited, which was possibly due to the magnifying of systematic errors in the disparity estimation compared with weight estimation. Despite this, abnormal biometry was an independent contributor for the poor prognosis of neonates.

Seroepidemiological map of Toxoplasma gondii infection and associated risk factors in preconception period in China: A nationwide cross-sectional study.

AIM: The aims of this study were to investigate the regional differences in seroepidemiology of toxoplasmosis in preconception period among Chinese women of reproductive age and to evaluate associated risk factors. METHODS: This national, population-based, cross-sectional serosurvey covered all 31 provinces and province-level municipalities in Mainland China. Married women intending to get pregnant within 6 months between 2010 and 2012 were recruited. Information on demographic characteristics (age, place of residence, occupation, dietary habits and exposure to cat) was obtained using interviews, and venous blood samples were collected to screen for Toxoplasma gondii infection. RESULTS: Of 2 008 561 women recruited to the study, 45 405 (2.3%) were Toxoplasma gondii IgG positive, and 6884 (0.3%) were IgM positive. Geographical variation for seropositivity ranged from 0.2% in Heilongjiang to 11.2% in Tianjing for IgG and from 0% in Tibet to 0.9% in Anhui for IgM. Advanced maternal age, occupation of a farmer, vegetarian diet and exposure to cat was significantly associated with Toxoplasma gondii IgM seropositivity, and its association with occupation of farmer and exposure to cat was significant after adjusting for province of residence (P < 0.05). CONCLUSION: There were significant regional variations in Toxoplasma gondii seropositivity and associated risk factors among Chinese women of reproductive age during preconception period. This calls for a targeted primary prevention strategy. Screening and treatment before conception and preconception health education may have potential for reducing congenital Toxoplasmosis in China.

Hepatitis B Virus Infection in Preconception Period Among Women of Reproductive Age in Rural China - A Nationwide Study.

BACKGROUND: Hepatitis B virus (HBV) infection during pregnancy is associated with perinatal complications and poor maternal and fetal outcomes. There is a lack of reports on HBV infection screening, prophylaxis, and/or treatment in preconception period among women planning a pregnancy. This study is to investigate the prevalence and demographic characteristics of HBV infection among rural women of reproductive age planning pregnancy within 6 months, in different geographical regions of China. METHODS: A population-based, cross-sectional, sero-survey of HBV infection among women intending to get pregnant within 6 months was carried out as a part of the National Free Preconception Health Examination Project covering 31 provinces in mainland China between 2010-12. General information (age, residence status, race, education, and occupation), HBV infection and vaccination history was collected. Results of HBV serological test panel were recorded for analysis. RESULTS: Of 2 120 131 women, 2 028 361 (95.7%) samples of HBV serology were available for analysis. Participating women were of young age (median 28.1 years), mostly engaged in agricultural activities (78.1%), and had high school education or lower (89.6%). The overall prevalence of HBsAg sero-positivity was 4.9%, which corresponds to an intermediate epidemic, with a wide geographical variation that ranged from 1.1% in Shanxi to 13.0% in Tibet. 90.1% women were susceptible to HBV with a 24.5% self-reported HBV vaccination rate. CONCLUSIONS: Significant regional differences in HBV prevalence, and a vast majority of women of childbearing age being susceptible to HBV, calls for a targeted HBV screening and vaccination strategy for women and their offspring in rural China.

Maternal serum bisphenol A levels and risk of pre-eclampsia: a nested case-control study.

Background: Although recent studies have indicated the potential adverse effects of maternal bisphenol A (BPA) exposure on pregnancy such as increasing the risk of pre-eclampsia, epidemiological evidence is limited. We aimed to evaluate the relationship between maternal BPA exposure and the risk of pre-eclampsia. Methods: We conducted a nested case-control study among 173 women (74 cases of pre-eclampsia and 99 controls). BPA concentrations were measured using liquid chromatography-mass spectrometry in the maternal serum samples collected during 16-20 gestational weeks. Multivariate logistic models were used to examine the relationship between maternal serum BPA concentrations and the risk of pre-eclampsia. Results: BPA was detectable (>0.1 µg/l) in 78.6% of the maternal serum samples at three levels: low (<2.24 µg/l), medium (2.24-4.44 µg/l), and high (>4.44 µg/l). BPA concentrations were significantly higher in the serum samples collected from the pre-eclampsia cases than those from controls (median: 3.40 vs. 1.50 µg/l, P < 0.01). With adjustment for maternal age, primiparous and BMI, the odds of developing pre-eclampsia were significantly elevated in subjects with high serum BPA levels compared with those with low levels (adjusted OR = 16.46, 95%CI = 5.42-49.85) regardless of subcategories of pre-eclampsia including severity and onset time. Among the pre-eclampsia subjects, the maternal serum concentration of BPA was not different between the early- and late-onset subjects (median: 3.09 vs. 3.50 µg/l, P = 0.57), but surprisingly higher in mild pre-eclampsia subjects compared with severe pre-eclampsia subjects (median: 5.20 vs. 1.80 µg/l, P < 0.01). Conclusions: These results demonstrated that maternal exposure to high level of BPA could be associated with an increased risk of pre-eclampsia.

A new perspective on universal preconception care in China.

Many risk factors associated with adverse pregnancy outcomes can be identified and modified preconceptionally. Despite a broad consensus that preconception care should be provided to all couples of reproductive age, it has not been integrated in routine healthcare. There are several barriers to its implementation, and even in the most resourceful countries, it is only provided to some select high-risk groups, rather than being an organized healthcare service provision to all. Recently, China seems to be leading the way by implementing preconception care nationwide in all rural areas. Its National Free Preconception Health Examination Project is a unique model of comprehensive preconception care. Advantages of this ambitious project are now becoming evident and benefiting the most vulnerable sections of Chinese society. This commentary provides an overview of National Free Preconception Health Examination Project and highlights the concepts that could be further developed and adapted into a model of preconception care.

China's community-based strategy of universal preconception care in rural areas at a population level using a novel risk classification system for stratifying couples´ preconception health status.

BACKGROUND: Preconception care (PCC) is recommended for optimizing a woman's health prior to pregnancy to minimize the risk of adverse pregnancy and birth outcomes. We aimed to evaluate the impact of strategy and a novel risk classification model of China´s "National Preconception Health Care Project" (NPHCP) in identifying risk factors and stratifying couples' preconception health status. METHODS: We performed a secondary analysis of data collected by NPHCP during April 2010 to December 2012 in 220 selected counties in China. All couples enrolled in the project accepted free preconception health examination, risk evaluation, health education and medical advice. Risk factors were categorized into five preconception risk classes based on their amenability to prevention and treatment: A-avoidable risk factors, B- benefiting from targeted medical intervention, C-controllable but requiring close monitoring and treatment during pregnancy, D-diagnosable prenatally but not modifiable preconceptionally, X-pregnancy not advisable. Information on each couple´s socio-demographic and health status was recorded and further analyzed. RESULTS: Among the 2,142,849 couples who were enrolled to this study, the majority (92.36%) were from rural areas with low education levels (89.2% women and 88.3% men had education below university level). A total of 1463266 (68.29%) couples had one or more preconception risk factors mainly of category A, B and C, among which 46.25% were women and 51.92% were men. Category A risk factors were more common among men compared with women (38.13% versus 11.24%; P = 0.000). CONCLUSIONS: This project provided new insights into preconception health of Chinese couples of reproductive age. More than half of the male partners planning to father a child, were exposed to risk factors during the preconception period, suggesting that an integrated approach to PCC including both women and men is justified. Stratification based on the new risk classification model demonstrated that a majority of the risk factors are avoidable, or preventable by medical intervention. Therefore, universal free PCC can be expected to improve pregnancy outcomes in rural China.