Subtypes of Job Satisfaction and Health-Related Quality of Life in Chinese Male Nurses: A Latent Profile Analysis.

In this cross-sectional study, we aimed to identify subgroups of job satisfaction and health-related quality of life (HRQoL) in Chinese male nurses and examine the factors associated with subgroup profiles. A convenience sample of 626 Chinese male nurses were enrolled from January to October 2021. Latent profile analysis was performed to identify profiles based on self-esteem, psychological resilience, social support, neuroticism, perceived prejudice, occupational stress, job satisfaction, and HRQoL. Chi-squared tests were used to examine predictors of profiles. Results indicated that a three-profile model provided the best fit: low job satisfaction and health (9.90%), moderate job satisfaction and health (64.06%), and high job satisfaction and health (26.04%). The average number of monthly night shifts was negatively correlated with the male nurses' subgroups. Psychological resilience, social support, and neuroticism were the key factors associated with the HRQoL of male nurses, while perceived prejudice, occupational stress, and self-esteem were the key factors associated with job satisfaction. Nurse administrators could improve their job satisfaction and health by reducing perceived prejudice, and job stress, increasing organizational support and resilience.

Association of preterm birth and birth size status with neurodevelopmental and psychiatric disorders in spontaneous births.

Preterm birth (PTB) or small birth size are risk factors for certain neurodevelopmental disorders. The magnitude of these associations in spontaneous births, and of associations for combined PTB and birth size status on neurodevelopmental and psychiatric disorders is unexplored. We investigated whether PTB and small/large for gestational age (SGA/LGA), separately or combined, in spontaneous births, are associated with a wide spectrum of neurodevelopmental and psychiatric disorders. In this population-based registry cohort study, all singleton spontaneous births in Finland from 1996 to 2014 were followed until 2018 (n = 819 764). We show that PTB across gestational ages, and SGA, were associated with higher risks for anxiety disorders, intellectual disabilities, specific developmental disorders (SDD), autism spectrum disorders (ASD), attention-deficit/hyperactivity disorders (ADHD) and other emotional and behavioural disorders (F98). Most of these associations were not attributed to familial factors. Larger effect sizes were observed with lower gestational ages. Extremely PTB was associated at highest risks with intellectual disabilities (HR, 10.70 [95%CI, 8.69-13.17]) and SDD (HR, 8.91 [95%CI, 8.18-9.71]). Moreover, very preterm birth combined with SGA was associated with a higher risk for SDD (HR, 7.55 [95%CI, 6.61-8.62]) than that of very preterm or SGA birth alone. Conversely, LGA birth lowered the risk for SDD and other emotional and behavioural disorders among individuals born very preterm. In conclusion, PTB along with SGA is associated with higher risks for SDD than one exposure alone, whereas LGA lowers the risks for SDD and other emotional and behavioural disorders in individuals born spontaneously.

[Neuropsychological development of large for gestational age infants at the age of 12 months]. / 大于胎龄儿12æœˆé¾„ç¥žç»å¿ƒç†å‘è‚²çŠ¶å†µç ”ç©¶.

OBJECTIVES: To investigate the level of neuropsychological development in large for gestational age (LGA) infants at the age of 12 months. METHODS: The infants, aged 12 to <13 months, who attended the Outpatient Service of Child Care in the First Affiliated Hospital of Shandong First Medical University from December 2021 to June 2023, were enrolled as subjects. According to the gestational age and birth weight, they were divided into preterm appropriate for gestational age (AGA) group, preterm LGA group, early term AGA group, early term LGA group, full-term AGA group, and full-term LGA group. A modified Poisson regression analysis was used to investigate the association between LGA and neuropsychological development outcome at 12 months of age. RESULTS: After adjustment for confounding factors, compared with the full-term AGA group at the age of 12 months, the full-term LGA group had a significant increase in the risk of language deficit (RR=1.364, 95%CI: 1.063-1.750), the early term LGA group had significant increases in the risk of abnormal gross motor, fine motor, language, and the preterm LGA group had significant increases in the risk of abnormal language, social behavior, and total developmental quotient (P<0.05); also, the early term AGA group had higher risks of developmental delay across all five attributes and in total developmental quotient at the age of 12 months (P<0.05); except for the language attribute, the preterm AGA group had higher risks of developmental delay in the other 4 attributes (P<0.05). CONCLUSIONS: The neuropsychological development of LGA infants with different gestational ages lags behind that of full-term AGA infants at 12 months of age, and follow-up and early intervention of such infants should be taken seriously in clinical practice.

Birth outcomes in mothers with hypertensive disorders and polycystic ovary syndrome: a population-based cohort study.

STUDY QUESTION: Is polycystic ovary syndrome (PCOS) associated with higher risks of extreme birth size and/or preterm birth in mothers with different hypertension types? SUMMARY ANSWER: PCOS was associated with additional risks of preterm birth in mothers with chronic hypertension and in singleton pregnancies of mothers with pre-eclampsia, and with higher risks of offspring born large for gestational age (LGA) in mothers with gestational hypertension. WHAT IS KNOWN ALREADY: Women with PCOS are more likely to develop gestational hypertension, pre-eclampsia, and chronic hypertension. Although adverse birth outcomes have been frequently reported in mothers with PCOS, such associations in the setting of a hypertensive disorder remain unknown. STUDY DESIGN SIZE DURATION: This is a population-based cohort study including all live births 2004-2014 in Finland (n = 652 732). To ensure diagnosis specificity, mothers with diagnoses that could cause signs and symptoms resembling PCOS were excluded. PARTICIPANTS/MATERIALS SETTING METHODS: Maternal diagnoses of PCOS, gestational hypertension, chronic hypertension, and pre-eclampsia were identified from the Finnish national registries. Generalized estimating equation and multivariable logistic regression were used to assess the adjusted odds ratio (aOR) and 95% CIs of preterm birth, very preterm birth, and offspring being small for gestational age (SGA) or LGA in hypertensive mothers with or without PCOS, using normotensive mothers without PCOS as reference. MAIN RESULTS AND THE ROLE OF CHANCE: Of 43 902 (6.7%) mothers with hypertensive disorders, 1709 (3.9%) had PCOS. Significant interactions were detected for PCOS with hypertension on preterm birth, very preterm birth, offspring born SGA and LGA (Fpreterm = 504.1, Pinteraction < 0.001; Fvery preterm = 124.2, Pinteraction < 0.001; FSGA = 99.5, Pinteraction < 0.001; FLGA = 2.7, Pinteraction = 0.012, respectively). Using mothers with no hypertensive disorder and no PCOS as reference, the risks of preterm and very preterm birth were overrepresented in non-PCOS mothers with chronic hypertension or pre-eclampsia. PCOS was associated with higher risks of preterm birth (aORPCOS 4.02, 3.14-5.15 vs aORnon-PCOS 2.51, 2.32-2.71) in mothers with chronic hypertension, with significant interaction between the exposures (F = 32.7, Pinteraction < 0.001). PCOS was also associated with a higher risk of preterm birth in singleton pregnancies of mothers with pre-eclampsia (aORPCOS 7.33, 5.92-9.06 vs aORnon-PCOS 5.72, 5.43-6.03; F = 50.0, Pinteraction < 0.001). Furthermore, the associations of PCOS comorbid with chronic hypertension or pre-eclampsia was detected also for spontaneous births. Moreover, the risk of offspring LGA was higher in mothers with PCOS and gestational hypertension although lower in those with gestational hypertension alone (aORPCOS 2.04, 1.48-2.80 vs aORnon-PCOS 0.80, 0.72-0.89; F = 9.7, Pinteraction = 0.002), whereas for offspring SGA, the risks were comparable between hypertensive mothers with and those without PCOS. LIMITATIONS REASONS FOR CAUTION: Information on medication treatment, gestational weeks of onset for pre-eclampsia and gestational hypertension, weight gain during pregnancy, and PCOS phenotypes were not available. All diagnoses were retrieved from registries, representing only those seeking medical care for their symptoms. The ICD-9 codes used to identify PCOS before year 1996 are known to underestimate the prevalence of PCOS, while the inclusion of anovulatory infertility as PCOS might introduce an overrepresentation bias, although PCOS constitutes 80% of anovulatory infertility. The risk of very preterm birth in relation to maternal PCOS and hypertensive disorders should be interpreted with caution owing to limited sample sizes. Multifetal pregnancies among maternal PCOS were too few for a subgroup analysis. Moreover, ART included IVF/ICSI only. Potential effects of other treatments, such as ovulation induction, were not examined. WIDER IMPLICATIONS OF THE FINDINGS: PCOS was associated with additional risks of preterm birth or offspring being LGA in hypertensive mothers, which varied between hypertension types. The exacerbated risks highlight consideration of PCOS in pregnancy counseling and management for women with hypertensive disorders. STUDY FUNDING/COMPETING INTERESTS: This study was supported by Shandong Provincial Natural Science Foundation, China [ZR2020MH064 to X.C.], the joint research funding of Shandong University and Karolinska Institute [SDU-KI-2019-08 to X.C. and C.L.], the Finnish Institute for Health and Welfare: Drug and pregnancy project [M.G.], the Swedish Research Council [2022-01188 to C.L.], the regional agreement on medical training and clinical research (ALF) between Stockholm County Council and Karolinska Institute Stockholm County Council [RS2021-0855 to C.L.], the Swedish Brain Foundation [FO2021-0412 to C.L.]. The funders had no role in study design, data collection, analysis, and interpretation, writing of the report or decision to submit for publication. The authors report no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

Association of maternal polycystic ovary syndrome and diabetes with preterm birth and offspring birth size: a population-based cohort study.

STUDY QUESTION: Is the presence of polycystic ovary syndrome (PCOS) associated with more adverse infant outcomes in mothers with different types of diabetes? SUMMARY ANSWER: The presence of PCOS implies higher risks of total (medically indicated and spontaneously combined) and spontaneous preterm birth in mothers with non-insulin-treated type 2 diabetes and gestational diabetes mellitus (GDM), and lower risk of offspring being large for gestational age (LGA) in mothers with insulin-treated diabetes. WHAT IS KNOWN ALREADY: PCOS is suggested to be an independent risk factor for adverse infant outcomes, and it is highly prevalent in mothers with diabetes. However, the impact of PCOS on the associations of different types of maternal diabetes with preterm birth and offspring birth sizes has not been reported. STUDY DESIGN, SIZE, DURATION: This is a population-based cohort study including all live births between 1996 and 2014 in Finland. Children with concurrent maternal diagnoses that could cause signs and symptoms similar to PCOS were excluded. A total of 1 097 753 children were included. PARTICIPANTS/MATERIALS, SETTING, METHODS: National registries were linked to identify births with maternal PCOS (n = 24 682), stratified by diabetes types. Logistic regression was used to examine the association of maternal PCOS and comorbid insulin-treated diabetes, non-insulin-treated type 2 diabetes or GDM with offspring LGA and small for gestational age (SGA). Generalized estimating equation was used to assess the risk of preterm birth in relation to maternal PCOS and diabetes. Potential interaction between PCOS and diabetes was evaluated on both additive and multiplicative scales. MAIN RESULTS AND THE ROLE OF CHANCE: Using mothers with no PCOS and no diabetes as the reference and adjusting for maternal and birth factors, there were higher risks of total (odds ratio (OR) 2.84, 95% CI 2.21 - 3.66 vs. OR 1.91, 95% CI 1.77 - 2.07, P = 0.01) and spontaneous (OR 4.02, 95% CI 2.94 - 5.50 vs. OR 2.35, 95% CI 2.13 - 2.59, P = 0.001) preterm birth for those with PCOS in mothers with non-insulin-treated type 2 diabetes and higher risks of total (OR 1.42, 95% CI 1.27-1.58 vs. OR 0.89, 95% CI 0.86-0.91, P = 0.0001) and spontaneous (OR 1.80, 95% CI 1.59-2.05 vs. OR 1.01, 95% CI 0.98-1.05, P = 0.0001) preterm birth for those with PCOS in mothers with GDM. Among mothers with type 2 diabetes, further adjusting for maternal BMI eliminated the difference in preterm birth risks between those with and those without PCOS, and adjustment for infertility treatment and pre-eclampsia also reduced the preterm risks associated with PCOS significantly. For mothers with GDM, however, the risks of total and spontaneous preterm birth remained higher for those with PCOS following these aforementioned adjustments or stratified analysis. The risk of offspring being LGA was lower for those with PCOS than those without PCOS among mothers with insulin-treated diabetes (OR 18.90, 95% CI 14.21-25.14 vs. OR 32.04, 95% CI 29.79-34.46, P = 0.0001), showing departure from additivity (relative excess risk due to interaction -11.74, 95% CI -16.17 to -7.31, P < 0.001) and multiplicativity (P < 0.001). PCOS did not alter the risk estimate of preterm birth in mothers with insulin-treated diabetes or offspring LGA and SGA in mothers with type 2 diabetes or GDM. LIMITATIONS, REASONS FOR CAUTION: The register-based diagnoses used in this study captured only women with PCOS seeking medical care and having live births. Including female infertility associated with anovulation as PCOS exposure was a risk for misclassification. Sample sizes for pregestational diabetes were small. Insulin purchase during pregnancy in those without a diabetes diagnosis was not accounted for in the analysis. For patients treated with insulin or other medications, we were unable to assess how they complied with such prescriptions. Also, maternal BMI was recorded only once in early pregnancy, thus the potential influence of gestational weight gain on birth outcomes could not be examined. Data on the causes for preterm birth were not available from the registers. WIDER IMPLICATIONS OF THE FINDINGS: The presence of PCOS implied higher risks of total and spontaneous preterm birth in mothers with type 2 diabetes or GDM, and lower risk of offspring being LGA in mothers with insulin-treated diabetes. The higher risks of preterm birth added by PCOS could be explained by prepregnancy BMI or in part by infertility treatment and pre-eclampsia in maternal non-insulin-treated type 2 diabetes, but not in maternal GDM. The differential effects of PCOS on the associations of different types of maternal diabetes with infant outcomes have implications for preventative strategies and clinical counseling for affected pregnancies. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by Shandong Provincial Natural Science Foundation, China (ZR2020MH064 to X.C.), Shandong Province Medical and Health Technology Development Plan (2018WS338 to X.C.), the joint research funding of Shandong University and Karolinska Institute (SDU-KI-2019-08 to X.C. and C.L.), the Finnish National Institute for Health and Welfare: Drug and pregnancy project (M.G.), the Swedish Research Council (2014-10171 to C.L.), the regional agreement on medical training and clinical research (ALF) between Stockholm County Council and Karolinska Institute Stockholm County Council (SLL20170292 and SLL20190589 to C.L.), the Swedish Brain Foundation (FO2019-0201 and FO2020-0305 to C.L.). X.C. received grants from the China Scholarship Council at the beginning of the study. The authors have no competing interests to disclose. TRIAL REGISTRATION NUMBER: N/A.

Association of Preeclampsia and Perinatal Complications With Offspring Neurodevelopmental and Psychiatric Disorders.

Importance: Maternal preeclampsia has been reported to increase the risk of autism spectrum disorder, attention-deficit/hyperactivity disorder (ADHD), and intellectual disability in offspring. However, the association between maternal preeclampsia combined with perinatal complications and neurodevelopmental and psychiatric disorders in offspring is less well documented. Objective: To examine the association of maternal preeclampsia, separately and together with perinatal complications, with neurodevelopmental and psychiatric disorders in offspring. Design, Setting, and Participants: This population-based cohort study used data from nationwide registries in Finland to assess all singleton live births (N = 1 012 723) between January 1, 1996, and December 31, 2014. Offspring were followed up until December 31, 2018 (when the oldest reached age 22 years). Exclusion criteria were maternal inpatient psychiatric diagnoses and pregestational diabetes. The study and data analysis were conducted from May 1, 2020, to June 1, 2021. Exposures: Preeclampsia and perinatal complications (delivery earlier than 34 weeks' gestation and/or small for gestational age). Main Outcomes and Measures: The primary outcomes were neurodevelopmental and psychiatric diagnoses and dispensation of psychotropic drugs among offspring until December 31, 2018. Cox proportional hazards regression analyses were performed to assess the associations. Results: Of 1 012 723 singleton live births (51.1% boys; mean [SD] maternal age at birth, 30.0 [5.4] years; specific data on race and ethnicity were not available in the data set), 21 010 children (2.1%) were exposed to preeclampsia alone, 33 625 children (3.3%) were exposed to perinatal complications alone, and 4891 children (0.5%) were exposed to both preeclampsia and perinatal complications. A total of 93 281 children (9.2%) were diagnosed with a neurodevelopmental or psychiatric disorder. Offspring exposed to both preeclampsia and perinatal complications had an increased risk of any neurodevelopmental or psychiatric disorder after adjusting for potential confounding (adjusted hazard ratio [aHR], 2.11; 95% CI, 1.96-2.26) compared with those not exposed to either preeclampsia or perinatal complications; this risk was higher than exposure to either preeclampsia alone (aHR, 1.18; 95% CI, 1.12-1.23) or perinatal complications alone (aHR, 1.77; 95% CI, 1.72-1.82). Sibling pair analyses did not detect any increase in the risk of neurodevelopmental or psychiatric disorders after exposure to preeclampsia alone, but offspring exposed to both preeclampsia and perinatal complications had increased risks of intellectual disabilities (aHR, 3.24; 95% CI, 1.05-10.06), specific developmental disorders (aHR, 3.56; 95% CI, 2.35-5.41), ADHD and conduct disorders (aHR, 2.42; 95% CI, 1.09-5.39), and other behavioral and emotional disorders (aHR, 2.45; 95% CI, 1.17-5.13). The risk estimates for specific developmental disorders (aHR, 2.82; 95% CI, 2.60-3.05) and ADHD and conduct disorders (aHR, 1.88; 95% CI, 1.65-2.14) were higher among offspring exposed to both preeclampsia and perinatal complications compared with those exposed to perinatal complications alone (aHR, 2.26 [95% CI, 2.18-2.33] and 1.60 [95% CI, 1.52-1.68], respectively). Conclusions and Relevance: In this study, exposure to both maternal preeclampsia and perinatal complications was associated with intellectual disabilities, specific developmental disorders, ADHD and conduct disorders, and other behavioral and emotional disorders in offspring. For specific developmental disorders and ADHD and conduct disorders, the risk estimates were higher among offspring exposed to both preeclampsia and perinatal complications compared with those exposed to perinatal complications only.

SRT1720 enhances maturity and quality of oocytes in aged mice.

This study aims to investigate the morphology and distribution of mitochondria, spindles, and chromosomes in oocytes of aged mice and examine the effects of SRT1720 on oocyte maturation. C57BL/6J mice were divided into young (4-8 weeks) and aged groups (48-52 weeks). In vitro maturation media contained (0.05, 0.1, and 1.0 µM) SRT1720 and 0.1-µM dimethyl sulfoxide (DMSO control). The rate of chromosome misalignment and spindle misorientation in oocytes of aged mice were significantly higher than that of young mice (P < 0.01). Fluorescence intensity of mitochondria from oocytes of aged mice was significantly lower than that of young mice (P < 0.01). SRT1720 at 0.1 µM significantly improved oocyte maturation, fertilization, and blastocyst formation in aged mice compared with young mice (P < 0.01). Additionally, immunofluorescence intensity of mitochondria, normal spindle morphology, and chromosome alignment were notably enhanced with SRT1720 when compared with the DSMO control group for metaphase II (MII)-stage oocytes matured in vitro (P < 0.01); 0.1-µM SRT1720 enhanced the expression level of SRIT1 in oocytes from aged mice. In summary, the aged mice oocytes showed increased nuclear and cytoplasmic defects, whereas SRT1720 enhanced oocyte maturation and quality. We concluded that 0.1-µM SRT1720 was an appropriate concentration for in vitro maturation media.

Association of maternal polycystic ovary syndrome or anovulatory infertility with obesity and diabetes in offspring: a population-based cohort study.

STUDY QUESTION: Are children of mothers with polycystic ovary syndrome (PCOS) or anovulatory infertility at increased risks of obesity or diabetes? SUMMARY ANSWER: Maternal PCOS/anovulatory infertility is associated with an increased risk of offspring obesity from early age and diabetes in female offspring from late adolescence. WHAT IS KNOWN ALREADY: Women with PCOS often have comorbid metabolic disorders such as obesity and diabetes, and children of mothers with PCOS have an increased risk of subtle signs of cardiometabolic alterations. STUDY DESIGN, SIZE, DURATION: This was a nationwide cohort study of all live births (n = 1 105 997) during 1996-2014 in Finland, excluding those with maternal diagnoses sharing signs and symptoms with PCOS (n = 8244). A total of 1 097 753 births were included and followed up until 31 December 2018. PARTICIPANTS/MATERIALS, SETTING, METHODS: National registries were linked to identify births with maternal PCOS or anovulatory infertility (n = 24 682). The primary outcomes were diagnoses of obesity (ICD-10: E65, E66) and diabetes (ICD-10: E10-E14) in offspring recorded in the Finnish Care Register for Health Care. Cox proportional hazards regression was modeled to analyze the risk of offspring obesity and diabetes in relation to prenatal exposure to maternal PCOS/anovulatory infertility. Differently adjusted models and stratified analyses were used to assess whether the risk was modified by maternal obesity or diabetes diagnoses, pre-pregnancy BMI, fertility treatment or perinatal problems. MAIN RESULTS AND THE ROLE OF CHANCE: Exposure to maternal PCOS/anovulatory infertility was associated with a higher cumulative incidence of obesity in the children (exposed: 1.83%; 95% CI 1.66-2.00% vs unexposed: 1.24%; 95% CI 1.22-1.26%). Accounting for birth factors and maternal characteristics such as obesity and diabetes diagnoses, the hazard ratio (HR) for obesity was increased in offspring below 9 years of age (HR 1.58; 95% CI 1.30-1.81), and in those 10-16 years of age (HR 1.37; 95% CI 1.19-1.57), but not in those aged 17-22 years (HR 1.24; 95% CI 0.73-2.11). Sex-stratified analyses revealed similar risk estimates for boys (HR 1.48; 95% CI 1.31-1.68) and girls (HR 1.45; 95% CI 1.26-1.68). Notably, the joint effect of PCOS/anovulatory infertility and BMI-based pre-pregnancy obesity on offspring obesity (HR 8.89; 95% CI 7.06-11.20) was larger than that of either PCOS/anovulatory infertility or obesity alone. Furthermore, PCOS/anovulatory infertility was associated with offspring obesity in children without perinatal problems (HR 1.27; 95% CI 1.17-1.39), with larger effect size for maternal PCOS/anovulatory infertility and joint perinatal problems (HR 1.61; 95% CI 1.35-1.91). However, the risk estimates were comparable between maternal PCOS/anovulatory infertility with (HR 1.54; 95% CI 1.17-2.03) and without fertility treatment (HR 1.46; 95% CI 1.32-1.61). For offspring diabetes, the HR was increased only between 17 and 22 years of age (HR 2.06; 95% CI 1.23-3.46), and specifically for Type 1 diabetes in females (HR 3.23; 95% CI 1.41-7.40). LIMITATIONS, REASONS FOR CAUTION: The prevalence of PCOS/anovulatory infertility in this study was 2.2%, lower than that reported in previous studies. In addition, the incidence of obesity in offspring was lower than that reported in studies based on measured or self-reported weight and height and may include mainly moderate and severe obesity cases who needed and/or actively sought medical care. Moreover, mothers with PCOS/anovulatory infertility were identified based on ICD codes, with no information on PCOS phenotypes. Furthermore, maternal pre-pregnancy BMI was available only from 2004. The PCOS/anovulatory infertility association with female offspring diabetes was based on only a few cases. Mothers' weight gain during pregnancy, use of fertility treatment other than fresh or frozen IVF/ICSI, offspring lifestyle, as well as fathers' age, medical disorders or medication prescriptions were not available for this study. WIDER IMPLICATIONS OF THE FINDINGS: These findings support that prenatal PCOS/anovulatory infertility exposure influences metabolic health in the offspring from early age. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by Shandong Provincial Natural Science Foundation, China [ZR2020MH064 to X.C.], Shandong Province Medical and Health Technology Development Plan [2018WS338 to X.C.], the joint research funding of Shandong University and Karolinska Institute [SDU-KI-2019-08 to X.C. and C.L.], the Finnish Institute for Health and Welfare: Drug and Pregnancy Project [M.G.], the Swedish Research Council [2014-10171 to C.L.], the regional agreement on medical training and clinical research (ALF) between Stockholm County Council and Karolinska Institute Stockholm County Council [SLL20170292 and SLL20190589 to C.L.], the Swedish Brain Foundation [FO2018-0141 and FO2019-0201 to C.L.]. X.C. received grants from the China Scholarship Council at the beginning of the study. The authors have no competing interests to disclose. TRIAL REGISTRATION NUMBER: N/A.

Association of polycystic ovary syndrome or anovulatory infertility with offspring psychiatric and mild neurodevelopmental disorders: a Finnish population-based cohort study.

STUDY QUESTION: Is maternal polycystic ovary syndrome (PCOS) associated with increased risks for a broad spectrum of psychiatric and mild neurodevelopmental disorders in offspring? SUMMARY ANSWER: Maternal PCOS and/or anovulatory infertility is independently, and jointly with maternal obesity, perinatal problems, cesarean delivery and gestational diabetes, associated with increased risks in offspring for almost all groups of psychiatric and mild neurodevelopmental disorders with onset in childhood or adolescence. WHAT IS KNOWN ALREADY: Maternal PCOS was previously associated with autism spectrum disorder, attention-deficit/hyperactivity disorders and possibly developmental delay in offspring. Few studies have investigated the association between maternal PCOS and other psychiatric and neurodevelopmental disorders in offspring. STUDY DESIGN, SIZE, DURATION: This was a population-based cohort study in Finland including all live births between 1996 and 2014 (n = 1 105 997). After excluding births to mothers with symptoms similar to PCOS, a total of 1 097 753 births by 590 939 mothers remained. Children were followed up until 31 December 2018, i.e. up to the age of 22 years. PARTICIPANTS/MATERIALS, SETTING, METHODS: National registries were used to link data of the included births and their mothers. Data from 24 682 (2.2%) children born to mothers with PCOS were compared with 1 073 071 (97.8%) children born to mothers without PCOS. Cox proportional hazards modeling was used to evaluate the hazard ratio (HR) and 95% CI for the risk of neuropsychiatric disorders in relation to maternal PCOS. Stratified analyses were performed to test the independent role of PCOS and the joint effects of PCOS with maternal obesity, perinatal problems, cesarean delivery, gestational diabetes and use of fertility treatment. The analysis was adjusted for maternal age, country of birth, marriage status at birth, smoking, parity, psychiatric disorders, prescription of psychotropic N05/N06 during pregnancy and systemic inflammatory diseases when applicable. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 105 409 (9.8%) children were diagnosed with a neurodevelopmental or psychiatric disorder. Firstly, maternal PCOS was associated with any psychiatric diagnosis (HR 1.32; 95% CI 1.27-1.38) in offspring. Particularly, the risk was increased for sleeping disorders (HR 1.46; 95% CI 1.27-1.67), attention-deficit/hyperactivity disorders and conduct disorders (HR 1.42; 95% CI 1.33-1.52), tic disorders (HR 1.42; 95% CI 1.21-1.68), intellectual disabilities (HR 1.41; 95% CI 1.24-1.60), autism spectrum disorder (HR 1.40; 95% CI 1.26-1.57), specific developmental disorders (HR 1.37; 95% CI 1.30-1.43), eating disorders (HR 1.36; 95% CI 1.15-1.61), anxiety disorders (HR 1.33; 95% CI 1.26-1.41), mood disorders (HR 1.27; 95% CI 1.18-1.35) and other behavioral and emotional disorders (ICD-10 F98, HR 1.49; 95% CI 1.39-1.59). In short, there was no significant difference between sexes. The results were robust when restricting the analyses to the first-born children or births to mothers without psychiatric diagnosis or purchase of psychotropic medication. Secondly, stratified analysis according to maternal BMI showed that the risk of any neuropsychiatric disorder was increased in offspring to normal-weight mothers with PCOS (HR 1.20; 95% CI 1.09-1.32), and markedly higher in those to severely obese mothers with PCOS (HR 2.11; 95% CI 1.76-2.53) compared to offspring to normal-weight mothers without PCOS. When excluding perinatal problems, mothers with PCOS were still associated with increased risks of any neuropsychiatric disorders in offspring (HR 1.28; 95% CI 1.22-1.34) compared to mothers without PCOS. However, an additional increase was observed for PCOS in combination with perinatal problems (HR 1.99; 95% CI 1.84-2.16). Likewise, excluding cases with maternal gestational diabetes (HR 1.30; 95% CI 1.25-1.36), cesarean delivery (HR 1.29; 95% CI 1.23-1.35) or fertility treatment (HR 1.31; 95% CI 1.25-1.36) did not eliminate the associations. LIMITATIONS, REASONS FOR CAUTION: The register-based prevalence of PCOS was lower than previously reported, suggesting that this study may capture the most severe cases. To combine anovulatory infertility with PCOS diagnosis as PCOS exposure might introduce diagnostic bias. It was not feasible to distinguish between subtypes of PCOS. Furthermore, familial factors might confound the association between maternal PCOS and neuropsychiatric disorders in offspring. Maternal BMI was available for birth cohort 2004-2014 only and there was no information on gestational weight gain. WIDER IMPLICATIONS OF THE FINDINGS: This study provides further evidence that maternal PCOS and/or anovulatory infertility, independently and jointly with maternal obesity, perinatal problems, gestational diabetes and cesarean delivery, implies a broad range of adverse effects on offspring neurodevelopment. These findings may potentially help in counseling and managing pregnancies. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the joint research funding of Shandong University and Karolinska Institute (SDU-KI-2019-08 to X.C and C.L.), THL Finnish Institute for Health and Welfare: Drug and pregnancy project [M.G.], the Swedish Research Council [2014-10171 to C.L.], the regional agreement on medical training and clinical research (ALF) between Stockholm County Council and Karolinska Institute Stockholm County Council [SLL20170292 to C.L.], the Swedish Brain Foundation [FO2018-0141 and FO2019-0201 to C.L.]. X.C. was supported by the China Scholarship Council during her training in Karolinska Institute. L.K. was supported by the China Scholarship Council for his PhD study in Karolinska Institute. The authors have no competing interests to disclose. TRIAL REGISTRATION NUMBER: N/A.

Relationship of prenatal maternal obesity and diabetes to offspring neurodevelopmental and psychiatric disorders: a narrative review.

Obesity and diabetes is a worldwide public health problem among women of reproductive age. This narrative review highlights recent epidemiological studies regarding associations of maternal obesity and diabetes with neurodevelopmental and psychiatric disorders in offspring, and provides an overview of plausible underlying mechanisms and challenges for future human studies. A comprehensive search strategy selected terms that corresponded to the domains of interest (maternal obesity, different types of diabetes, offspring cognitive functions and neuropsychiatric disorders). The databases searched for articles published between January 2010 and April 2019 were PubMed, Web of Science and CINAHL. Evidence from epidemiological studies strongly suggests that maternal pre-pregnancy obesity is associated with increased risks for autism spectrum disorder, attention-deficit hyperactivity disorder and cognitive dysfunction with modest effect sizes, and that maternal diabetes is associated with the risk of the former two disorders. The influence of maternal obesity on other psychiatric disorders is less well studied, but there are reports of associations with increased risks for offspring depression, anxiety, schizophrenia and eating disorders, at modest effect sizes. It remains unclear whether these associations are due to intrauterine mechanisms or explained by confounding family-based sociodemographic, lifestyle and genetic factors. The plausible underlying mechanisms have been explored primarily in animal models, and are yet to be further investigated in human studies.

The impact of unicornuate uterus on perinatal outcomes after IVF/ICSI cycles: a matched retrospective cohort study.

OBJECTIVE: To evaluate the impact of unicornuate uterus on perinatal outcomes after in vitro fertilization and/or intracytoplasmic sperm injection (IVF/ICSI) cycles. METHODS: We performed a retrospective cohort study including 160 women with unicornuate uterus and 1:1 matched controls with normally shaped uterus. They received IVF/ICSI treatment during January 2009 and December 2011. The perinatal outcomes were followed up till December 2014. RESULTS: There were no significant differences in pregnancy rate, clinical pregnancy rate or live birth rate (53.6 versus 52.7, 41.4 versus 43.5, 33.8% versus 31.8%) between unicornuate uterus group and controls. Their biochemical pregnancy rate (22.8 versus 17.5%) and miscarriage rate (16.0 versus 18.8%) were similar. No significant differences were identified in preterm birth rate (18.3 versus 11.8%), birthweight (3.24 ± 0.60 versus 3.33 ± 0.54 kg) or birth length (50.47 ± 2.33 versus 50.06 ± 2.40 cm) among the singletons. However, lower gestational age (35.56 ± 2.68 versus 36.71 ± 1.73, p = .019), higher preterm birth rate (55.0 versus 34.4%, p = .038), lower birthweight (2.33 ± 0.58 versus 2.69 ± 0.38 kg, p = .001), lower birth length (45.33 ± 2.46 versus 48.88 ± 2.06 cm, p = .000), as well as higher rate of very low birthweight (13.2% versus 0, p = .007) were found for the twins from unicornuate uterus group. CONCLUSIONS: The results indicated unimpaired pregnancy and perinatal outcomes for women with unicornuate uterus conceiving one fetus. However, close attention should be paid to twin pregnancy in unicornuate uterus owing to increased risks of prematurity and low birthweight. Selected single embryo transfer is recommended for women with unicornuate uterus undergoing IVF/ICSI cycles.

Impaired telomere length and telomerase activity in peripheral blood leukocytes and granulosa cells in patients with biochemical primary ovarian insufficiency.

STUDY QUESTION: Are telomere length and telomerase activity associated with biochemical primary ovarian insufficiency (POI)? SUMMARY ANSWER: Shortened telomere length and diminished telomerase activity were associated with biochemical POI. WHAT IS KNOWN ALREADY: POI is a result of pathological reproductive aging and encompasses occult, biochemical and overt stages. Studies have indicated telomere length as a biomarker for biological aging. STUDY DESIGN, SIZE, DURATION: A total of 120 patients with biochemical POI and 279 control women were recruited by the Center for Reproductive Medicine of Shandong University. PARTICIPANTS/MATERIALS, SETTING, METHODS: Telomere length in peripheral blood leukocytes (LTL) and granulosa cells (GTL) was measured using a modified Quantitative Polymerase Chain Reaction technique. The relative telomerase activity (RTA) in granulosa cells was detected using a modified quantitative-telomeric repeat amplification protocol assay. MAIN RESULTS AND THE ROLE OF CHANCE: After adjusting for age, patients with biochemical POI (n = 120) exhibited significantly shorter LTLs (0.75 ± 0.09 vs 1.79 ± 0.12, P < 0.001; OR = 0.54, 95% CI = 0.43-0.68) and GTLs (0.78 ± 0.09 vs 1.90 ± 0.23, P < 0.001; OR = 0.54, 95% CI = 0.41-0.70) than the controls (n = 279 for LTLs; n = 90 for GTLs). Significantly diminished RTAs in granulosa cells were detected in patients with biochemical POI (n = 31) compared with the controls (n = 38) (1.57 ± 0.59 vs 4.63 ± 0.93, P = 0.025; OR = 0.84, 95% CI = 0.72-0.98). LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: The cross-sectional nature of this study might have its limit in telomere length as well as telomerase activity along with the progressing decline in ovarian function. WIDER IMPLICATIONS OF THE FINDINGS: These findings suggest that telomere length and telomerase activity may be considered as indicators for progression of ovarian decline. STUDY FUNDING/COMPETING INTERESTS: This research was supported by the National Basic Research Program of China (973 Program) (2012CB944700), Science research foundation item of no-earnings health vocation (201402004) and the National Natural Science Foundation of China (31471352, 81270662, 81471509, 81300461, 81522018). The authors have no potential conflict of interest to declare.

Mutations in KISS1 are not responsible for idiopathic hypogonadotropic hypogonadism in Chinese patients.

PURPOSE: To investigate whether mutations in the KISS1 gene are present in 170 Chinese patients with idiopathic hypogonadotropic hypogonadism (IHH). METHODS: Mutational screening of the KISS1 gene was performed in 170 Chinese patients with IHH (133 male cases and 37 female cases) and 187 matched controls (94 males and 93 females). RESULTS: Two known single-nucleotide polymorphisms (SNP), c. 58G > A in exon 1 and c. 242C > G in exon 2, were identified. However, no difference of genotype and allelic frequencies between cases and controls was observed. CONCLUSIONS: The results suggest that mutations in the coding sequence of KISS1 are not common in patients with IHH in this Chinese population.

Mutation screening of HOXA7 and HOXA9 genes in Chinese women with Müllerian duct abnormalities.

HOXA genes in groups 7-13 have been proven to play a role in determining positional identity along the genitalia axis. The aim of the present study was to explore the relationship between HOXA7 and HOXA9 mutations and Müllerian duct abnormalities (MDA). One hundred and ninety-two Chinese patients with MDA abnormalities and 192 healthy controls were recruited. All coding regions of HOXA7 and HOXA9 were amplified and sequenced directly. Rs2301721 and rs2301720 in HOXA7, rs35355140 and rs7810502 in HOXA9 were identified in patients with MDA and controls. One rare single nucleotide polymorphism rs189587233 in 3' UTR of HOXA9 gene was detected in one patient with didelphic uterus and absent in the 192 controls. This polymorphism, however, is known to exist in the normal Chinese population. Our results indicated that variants in the HOXA7 and HOXA9 genes were not common in Chinese women with Müllerian duct abnormalities.

Mutations in HOXA11 are not responsible for Müllerian duct anomalies in Chinese patients.

As a member of the homeobox (HOX) gene family, HOXA11 is expressed in the primordia of lower uterus and cervix during fetal life and is essential for endometrial development and embryo implantation in the adults. The aim of the present study was to investigate whether mutations in HOXA11 contribute to Müllerian duct anomalies (MDA) in Chinese. A cohort of 192 patients with MDA and 192 healthy controls was enrolled. Genomic DNA was extracted. All exons and exon-intron boundaries were amplified and sequenced. One novel synonymous variant (c.774G>A) and one known single-nucleotide polymorphism were identified, both of which were not found in the matched controls. The results suggest that mutations in the coding region of HOXA11 are not common in Chinese women with MDA. As a member of the homeobox gene family, HOXA11 is expressed in the primordia of lower uterus and cervix during fetal life and is essential for endometrial development and embryo implantation in the adults. The aim of the present study was to investigate whether mutations in HOXA11 contribute to Müllerian duct anomalies (MDA) in Chinese. A cohort of 192 patients with MDA and 192 healthy controls was enrolled. Genomic DNA was extracted. All exons and exon-intron boundaries were amplified and sequenced. One novel synonymous variant (c.774G>A) and one known single-nucleotide polymorphism were identified, both of which were not found in the matched controls. The results suggest that mutations in the coding region of HOXA11 are not common in Chinese women with MDA.

[Simultaneous isolation and purification of gallic acid and brevifolincarboxylic acid from Polygonum capitatum by high-speed counter-current chromatography].

OBJECTIVE: To isolate and purify gallic acid and brevifolincarboxylic acid simultaneously by high-speed counter-current chromatography (HSCCC) from a crude extract of Polygonum capitatum. METHOD: The biphasic solvent system composed of ethyl acetate-n-butanol-0.44% acetic acid (3:1:5) was used at a flow rate of 2.0 mL x min(-1), while the aqueous phase was selected as the mobile phase and the apparatus was rotated at 860 r x min(-1). The effluent was detected at 272 nm. RESULT: 51.5 mg of gallic acid and 5.9 mg of brevifolincarboxylic acid were separated from 1.07 g of the crude extract with the purities of 99.7% and 97.5%, respectively, while brevifolincarboxylic acid was obtained firstly from the genus Polygonum. The structures of the compounds were identified by ultraviolet spectrometry (UV), infra-red spectrometry (IR), liquid chromatography/mass spectrometry (LC/MS), time-of-flight mass spectrometry( TOF-MS), 1H-nuclear magnetic resonance (NMR) and 13C-NMR. CONCLUSION: This method is feasible and rapid for isolation and purification of gallice acid and brevifolincarboxylil acid.

The opposing effect of hypoxia-inducible factor-2alpha on expression of telomerase reverse transcriptase.

Hypoxia-inducible factor-1alpha (HIF-1alpha) has been implicated in the transcriptional regulation of the telomerase reverse transcriptase (hTERT) gene expression and telomerase activity, essential elements for cellular immortalization and transformation. However, controversial results were obtained in different studies. Moreover, it is totally unclear whether HIF-2alpha, the paralog of HIF-1alpha, plays a role in regulating hTERT expression. In the present study, we found that hypoxic treatment enhanced hTERT mRNA expression and telomerase activity in three renal cell carcinoma (RCC) cell lines with different genetic backgrounds. Both HIF-1alpha and HIF-2alpha were capable of significantly increasing the hTERT promoter activity in these cells. Moreover, depleting HIF-2alpha led to a down-regulation of hTERT mRNA level in RCC A498 cells expressing constitutive HIF-2alpha. It was found that HIF-2alpha bound to the hTERT proximal promoter and enhanced the recruitment of the histone acetyltransferase p300 and histone H3 acetylation locally in A498 cells treated with hypoxia. Increased levels of hTERT mRNA were observed in two of three hypoxia-treated malignant glioma cell lines. However, HIF-1alpha stimulated whereas HIF-2alpha inhibited the hTERT promoter activity in these glioma cell lines. Ectopic expression of HIF-2alpha resulted in diminished hTERT expression in glioma cells. Collectively, HIF-1alpha activates hTERT and telomerase expression in both RCC and glioma cells, and HIF-2alpha enhances hTERT expression in RCC cells, whereas it represses the hTERT transcription in glioma cells. These findings reveal a complex relationship between HIF-1alpha/2alpha and hTERT/telomerase expression in malignant cells, which may have both biological and clinical implications.