Placental inflammatory cytokines mRNA expression and preschool children's cognitive performance: a birth cohort study in China.

BACKGROUND: The immunologic milieu at the maternal-fetal interface has profound effects on propelling the development of the fetal brain. However, accessible epidemiological studies concerning the association between placental inflammatory cytokines and the intellectual development of offspring in humans are limited. Therefore, we explored the possible link between mRNA expression of inflammatory cytokines in placenta and preschoolers' cognitive performance. METHODS: Study subjects were obtained from the Ma'anshan birth cohort (MABC). Placental samples were collected after delivery, and real-time quantitative polymerase chain reaction (RT-qPCR) was utilized to measure the mRNA expression levels of IL-8, IL-1ß, IL-6, TNF-α, CRP, IFN-γ, IL-10, and IL-4. Children's intellectual development was assessed at preschool age by using the Wechsler Preschool and Primary Scale of Intelligence, Fourth Edition (WPPSI-IV). Multiple linear regression and restricted cubic spline models were used for statistical analysis. RESULTS: A total of 1665 pairs of mother and child were included in the analysis. After adjusting for confounders and after correction for multiple comparisons, we observed that mRNA expression of IL-8 (ß = - 0.53; 95% CI, - 0.92 to - 0.15), IL-6 (ß = - 0.58; 95% CI, - 0.97 to - 0.19), TNF-α (ß = - 0.37; 95% CI, - 0.71 to - 0.02), and IFN-γ (ß = - 0.31; 95% CI, - 0.61 to - 0.03) in the placenta was negatively associated with preschoolers' full scale intelligence quotient (FSIQ). Both higher IL-8 and IL-6 were associated with lower children's low fluid reasoning index (FRI), and higher IFN-γ was associated with lower children's working memory index (WMI). After further adjusting for confounders and children's age at cognitive testing, the integrated index of six pro-inflammatory cytokines (index 2) was found to be significantly and negatively correlated with both the FSIQ and each sub-dimension (verbal comprehension index (VCI), visual spatial index (VSI), FRI, WMI, processing speed index (PSI)). Sex-stratified analyses showed that the association of IL-8, IFN-γ, and index 2 with children's cognitive development was mainly concentrated in boys. CONCLUSIONS: Evidence of an association between low cognitive performance and high expression of placental inflammatory cytokines (IL-8, IL-6, TNF-α, and IFN-γ) was found, highlighting the potential importance of intrauterine placental immune status in dissecting offspring cognitive development.

Thyroid function test abnormalities-isolated TPOAb+, SCH and hypothyroxinemia and preschool children's neurodevelopment.

OBJECTIVE: Thyroid function test abnormalities are frequent and associated with the offspring's adverse neurodevelopment. This study aimed to examine the relationship between maternal thyroid function test abnormalities before 20 gestational weeks and children's cognitive, emotional and behavioural development at 3-6 years of age. PATIENTS AND MEASUREMENTS: A total of 2243 mother-child pairs were included in the final analysis. Maternal thyroid function was evaluated retrospectively during the children's preschool period. The serum thyrotrophin, free thyroxine and thyroid peroxidase antibodies (TPOAb) were detected by chemiluminescence immunoassay during the follow-up period. The neurodevelopmental status of preschoolers aged 3-6 years was evaluated by parental versions of The Behavior Rating Inventory of Executive Function-Preschool and The Strengths and Difficulties Questionnaires. The associations between maternal thyroid function test abnormalities and preschoolers' neurodevelopment were examined using Poisson regression models. RESULTS: After adjusting for potential confounders in Poisson regression analyses, it showed that maternal isolated TPOAb positivity before 20 gestational weeks may be associated with the increased risk of abnormalities in peer problems (odds ratio [OR] = 1.90, 95% confidence interval [CI]: 1.26, 287). Maternal isolated SCH before 20 gestational weeks was observed to be related with increased risk of abnormalities in inhibition (OR = 2.73, 95% CI: 1.37, 5.41), working memory (OR = 1.67, 95% CI: 1.04, 2.70), conduct problems (OR = 1.80, 95% CI: 1.05, 3.09), hyperactivity (OR = 1.94, 95% CI:1.08, 3.49) and total difficulties (OR = 1.94, 95% CI: 1.13, 3.34). Maternal isolated hypothyroxinemia before 20 gestational was observed to be related with increased risk of abnormalities in peer problems (OR = 2.71, 95% CI: 1.17, 6.27). CONCLUSIONS: Thyroid function test abnormalities before 20 gestational weeks may be associated with children's neurodevelopment at 3-6 years of age.

Early sleep duration trajectories and children's cognitive development: a prospective cohort study.

We aimed to investigate the association between sleep duration trajectories and cognitive performance in preschool-aged Chinese children. We included 2131 children from the Ma'anshan birth cohort (MABC) study. Sleep duration trajectories from 6 to 48 months of age were determined using the group-based trajectory modeling (GBTM). Children's intellectual development was assessed using the Wechsler Preschool and Primary Scale of Intelligence. Compared to those with a medium total sleep duration trajectory, children with a short total sleep duration trajectory had poorer cognitive performance on the Visual Spatial Index (VSI) (ß = -3.65; 95% CI = -6.77 to -0.53), which was associated with an increased risk of a low full-scale intelligence quotient (FSIQ) (OR = 1.60; 95% CI = 1.02 to 2.51). The short total sleep duration trajectory was associated with a low VSI compared with both the medium total sleep duration trajectory and the long total sleep duration trajectory. Compared to children with normal nighttime sleep duration and normal daytime sleep duration trajectories, children with short nighttime sleep and long daytime sleep duration trajectories, normal nighttime sleep and long daytime sleep duration trajectories, and short nighttime sleep and normal daytime sleep duration trajectories all had lower cognitive performance. The restricted cubic spline (RCS) also showed that children with and appropriate total sleep duration, an adequate nighttime sleep duration, and a moderate daytime sleep duration had higher FSIQ. CONCLUSIONS: The results of this study emphasize that a medium total sleep duration, adequate sleep at nighttime, and appropriate sleep in the daytime appear to be more beneficial for children's cognitive development. WHAT IS KNOWN: • Sleep duration in infancy is strongly associated with neurocognitive development. WHAT IS NEW: • Medium and long total sleep duration trajectories are beneficial for children's cognitive performance compared to the short total sleep duration trajectory. • A medium total sleep duration, adequate sleep at nighttime and appropriate sleep in the daytime appear to be more beneficial for children's cognitive development.

Maternal pregnancy-related anxiety and children's physical growth: the Ma'anshan birth cohort study.

BACKGROUND: Epidemiological studies have identified maternal antenatal anxiety and several adverse birth outcomes, but limited studies have focused on the relationship with the long-term physical growth of children. The study aimed to assess the influence of maternal pregnancy-related anxiety on physical growth in children at different exposure periods during pregnancy. METHODS: 3,154 mother-child pairs were included based on the Ma'anshan birth cohort study. Maternal prenatal anxiety was obtained by administering a questionnaire using the pregnancy-related anxiety questionnaire (PRAQ) scale during the 1st, 2nd and 3rd trimesters of pregnancy. Body fat (BF) (48 to 72 months) and Body Mass Index (BMI) (birth to 72 months) were collected repeatedly for children. Group-based trajectory models were applied to fit the different trajectories of BMI and BF. RESULTS: Maternal anxiety in the 2nd (OR = 0.81; 95% CI: 0.68 to 0.98; P < 0.025) and 3rd (OR = 0.80; 95% CI: 0.67 to 0.97; P = 0.020) trimesters was associated with a decreased risk of rapid weight gain (RWG) in the first year of life. Children aged 48 to 72 months of mothers with anxiety in the 3rd trimester had lower BMI (ß = -0.161; 95% CI, -0.293 to -0.029; P = 0.017) and BF (ß = -0.190; 95% CI, -0.334 to -0.046; P = 0.010), and these children were less likely to develop a very high BMI trajectory (OR = 0.54; 95% CI: 0.34 to 0.84; P = 0.006), and a high BF trajectory (OR = 0.72; 95% CI: 0.53 to 0.99; P = 0.043). Similar associations were found between maternal anxiety in both 2nd and 3rd trimesters and children's physical growth. CONCLUSIONS: Offspring of mothers with prenatal anxiety in the 2nd and 3rd trimesters predicts poorer growth in infancy and preschool age. Early improvement and treatment of prenatal anxiety could benefit physical health and development in early childhood.

Birth outcomes and early growth patterns associated with age at adiposity rebound: the Ma'anshan birth cohort (MABC) study.

OBJECTIVE: Early onset of adiposity rebound (AR) is considered an early indicator of obesity risk. Our objective was to investigate the association of birth outcomes and early physical growth patterns with early AR in children. METHODS: Study subjects (n = 2705) were enrolled from the Ma'anshan birth cohort (MABC). The body mass index (BMI), head circumference, waist circumference, and body fat were collected. Rapid weight gain (RWG) was defined by the change in weight standard-deviation score in the first two years of life. Group-based trajectory modeling (GBTM) was used to determine children's physical growth trajectories. The age of AR was fitted using fractional polynomial function models. RESULTS: Children with very high BMI trajectories (RR = 2.83; 95% CI 2.33 to 1.40), rising BMI trajectories (RR = 3.15; 95% CI 2.66 to 3.72), high waist circumference trajectories (RR = 4.17; 95% CI 3.43 to 5.06), and high body fat trajectories (RR = 3.01; 95% CI 2.62 to 3.46) before 72 months of age were at a greater risk of experiencing early AR. Low birth weight (LBW) (RR = 1.86; 95% CI 1.28 to 2.51), preterm birth (PTB) (RR = 1.50; 95% CI 1.17 to 1.93), and small for gestational age (SGA) (RR = 1.37; 95% CI 1.14 to 1.64) associated with increased risk of early AR. Moreover, infants experiencing RWG (RR = 1.59; 95% CI 1.40 to 1.83), low BMI trajectories (RR = 1.27; 95% CI 1.06 to 1.53) and rising BMI trajectories (RR = 1.50; 95% CI 1.22 to 1.84) in the first two years were at higher risk of developing early AR subsequently. Compared to the group with non-early AR, the BMI of children with early AR tended to be lower first (from birth to 6 months of age) and then higher (from 18 to 72 months of age). CONCLUSIONS: Children with overall high BMI, high waist circumference, and high body fat before 72 months of age are more likely to experience early AR, but infants with low BMI trajectories, rising BMI trajectories and infants experiencing RWG in the first two years of life similarly increase the risk of early AR. These results can help to understand the early factors and processes that lead to metabolic risks.

Age at adiposity rebound and the relevance for obesity: a systematic review and meta-analysis.

OBJECTIVES: To understand the sex difference in age at adiposity rebound (AR), integrate the prevalence of early AR (EAR), and provide a quantitative association between early age at AR and overweight/obesity. METHODS: Literature review was conducted in different databases, including the Web of Science, PubMed, EMBASE, Wiley, Chinese National Knowledge Infrastructure, and ScienceDirect databases up to August 2021. Studies that reported data related to AR were considered for inclusion. Pooled effect sizes and their respective 95% confidence intervals (CIs) were calculated using random effects models, depending on the size of heterogeneity. Heterogeneity was tested by using the I2 statistics. RESULTS: 28 studies with a combined sample size of 106,397 people were included in the final meta-analysis. Girls had a significantly earlier age of AR than boys (mean difference = 3.38 months; 95% CI 2.14-4.63). The overall prevalence of EAR was 40% (95% CI 31% to 50%), and the prevalence in girls was 5% higher than that in boys based on the definition of age at AR < 5.0-5.1 years. The overall pooled prevalence of EAR showed an increasing trend by child's birth year [1934-1973]: 29% (95% CI 22% to 37%), 1991-2001: 35% (95% CI 26% to 44%), and 2002-2009: 52% (95% CI 40-63%). Early age at AR (age at AR < 5.0-5.1 years) was associated with a significantly increased risk of overweight/obesity (OR = 5.07; 95% CI 3.60-7.12), overweight (OR = 3.10; 95% CI 1.69-5.70), and obesity (OR = 6.97; 95% CI 4.32-11.26) from the preschool period to adulthood. CONCLUSIONS: The overall prevalence of EAR is increasing, and girls experience AR earlier than boys. The early age at AR in children may be an early and effective marker of obesity.

Sex-specific association between placental inflammatory cytokine mRNA expression and preschoolers' behavioral development: The Ma'anshan birth cohort study.

BACKGROUND: Placental inflammation may contribute to brain abnormalities and childhood neuropsychiatric disorders, but limited knowledge is available on the association of placental inflammatory cytokine levels and offspring's behavioral development. This study aimed to examine the sex-specific association between placental inflammatory cytokine mRNA expression and preschoolers' behavioral development. METHODS: 3474 pregnant women were recruited as the initial study population in the Ma'anshan birth cohort (MABC) study. Placentas (n = 2519) were collected during childbirth, and the mRNA expression of IL-8, IL-1ß, CRP, TNF-α, IL-6, IL-10, and IL-4 was assessed. The Child Behavior Checklist 1.5-5 (CBCL 1.5-5) was used to assess children's behavioral development at 4 years old. A T-score ≥ 60 on summary scales or a score ≥ 65 on syndrome scales was regarded as the borderline clinical range. Multiple linear regression models and binary logistic regression models were applied to explore the sex-specific associations between placental inflammatory cytokines mRNA transcript levels and preschoolers' behavioral development. RESULTS: Sex-specific associations between placental inflammatory cytokines mRNA expression and preschoolers' behavioral development were observed. There was a positive association between IL-8 and CBCL scores for boys on anxious/depressed problems, aggressive behaviors, externalizing problems and total problems. Logistic regression models showed that high levels of IL-8 were associated with a higher risk of girls' emotionally reactive problems and sleep problems compared to low/medium levels. High TNF-α was correlated with increased sleep problem scores in boys, and medium TNF-α (vs. low levels) was associated with an increased risk of girls' externalizing problems. Medium levels of CRP, IL-1ß, and IL-6 were found to be associated with a decreased risk of girls' behavioral problems compared to low/high levels. For anti-inflammatory cytokines, medium IL-10 and IL-4 (vs. low levels) were observed to be associated with a lower risk of internalizing problems in boys and externalizing problems in girls, respectively. High IL-10 was correlated with decreased attention problem scores in boys. CONCLUSION: This study indicates that placental inflammatory cytokine mRNA expression of IL-8, CRP, TNF-α, IL-1ß, IL-4 and IL-10 may be associated with preschoolers' behavioral development in a sex-specific manner.

Neuropsychological Study on the Effects of Boxing Upon Athletes' Memory.

ABSTRACT: Teng, Y, Yu, Q, Yu, X, Zhan, L, and Wang, K. Neuropsychological study on the effects of boxing upon athletes' memory. J Strength Cond Res 36(12): 3462-3467, 2022-This study attempts to explore the impairment of athletes' memory caused by 1 year of boxing training according to the n-back test and Chinese auditory learning test (CALT). Accordingly, 58 new athletes were prospectively analyzed from a sports school, where 28 athletes who received boxing training were regarded as the exposed group and 30 athletes who received matched training were taken as unexposed group for a duration of 1 year. All subjects respectively completed an n-back test (to test working memory) and a CALT test (to test short-term memory and long-term memory) before and after the training. During the tests, accuracy and reaction time from the n-back test and the correct number from CALT were recorded. The accuracy of the boxing group was observed to be lower than that of the matched group in the 2-back test ( p < 0.05), whereas the reaction time of the boxing group was longer than that of the matched group ( p < 0.05) after a year of boxing practice. The results of CALT1 (short-term memory), CALT8 (long-term memory), and CALT9 (recognition memory) were lower in the boxing group than that in the matched group after a year ( p < 0.05). The results suggest that exposure to 1 year of boxing training can impair the boxers' working memory, short-term memory, and long-term memory. Therefore, boxers should strengthen their head protection during training to avoid frequent impacts to the head.

Effect of anti-tumor necrosis factor α treatment on radiographic progression in patient with ankylosing spondylitis: A systematic review and meta-analysis.

BACKGROUND: Efficacy of anti-tumor necrosis factor (anti-TNF)α treatment in patient with active ankylosing spondylitis (AS) had been proved by many clinical studies. Inflammation and new bone formation in spine were two pivotal aspects in AS. TNF α inhibitor could eliminate inflammation including clinical and laboratory inflammatory manifestation. Paradoxical results whether TNF α antagonist could delay radiographic progression in AS were often been reported simultaneously. OBJECTIVES: To review the literature about the effect of TNF α inhibitor on radiographic progression and disease activity in patient with AS. METHODS: We conducted a comprehensive search including Medline, EMBASE and the Cochrane Library from 1 January 2000 to 15 August 2017. Two reviewers independently supplemented with hand searching for the reference lists of inclusion. All trials focusing on radiographic progression or disease activity in patients with AS treated with anti-TNF α agents. Primary outcomes were modified Stokes AS Spinal Score (mSASSS), as well as Bath AS disease activity index (BASDAI) and Bath AS functional index (BASFI). Two reviewers independently selected studies and analyzed data. Methodological quality was assessed using the Newcastle-Ottawa scale (NOS). We pooled effects recorded on different scales as Standardized mean differences (SMDs) with 95% confidence intervals (CIs) using random-effects models. RESULTS: We included 14 studies of low to moderate risk of bias with 3,186 patients, compared with control group, there was no effect of mSASSS changes (SMD = -0.12, 95% CI: -1.17-0.93, p value = .82, I2 = 95%) and follow-up (SMD = 0.03, 95% CI: 0.21-0.26, p value = .82, I2 = 36%) estimation in anti-TNF α group. However anti-TNF α agent treatment led to remarkable improvements on both Bath AS disease activity index (BASDAI) (SMD = 1.06, 95% CI: 0.22-1.89, p value = .01, I2 = 96%) and Bath AS functional index (BASFI) (SMD = 0.93, 95% CI: 0.24-1.92, p value = .01, I2 = 97%) scores at 12 weeks. CONCLUSION: Our meta-analysis found no significant effect on delaying radiographic progression in AS treated with TNF α inhibitor, although TNF α inhibitor could do improve significantly disease activity and physical function in AS.

The impact of maternal anxiety during pregnancy on children's eczema and allergic rhinitis: The Ma'anshan birth cohort study.

OBJECTIVE: The objective of this study was to investigate the associations between maternal exposure to anxiety during pregnancy and the susceptibility of offspring to eczema and allergic rhinitis and the possibility of sensitivity periods and cumulative effects. METHODS: The study's sample consisted of 3160 mother-child pairs from the Ma'anshan Birth Cohort Study. Maternal anxiety was repeatedly measured in the 1st, 2nd, and 3rd trimesters of pregnancy using the Chinese version of the Pregnancy-Related Anxiety Scale. Information regarding children's eczema and allergic rhinitis diagnoses was collected through parental reports at 12, 24, 36 and 48 months of age. Binary logistic regression models were used for statistical analysis and corrected for multiple comparisons using the false discovery rate (FDR) method. RESULTS: Children whose mothers experienced anxiety throughout pregnancy had the highest odds of developing total eczema (aOR 1.45, 95% CI 1.02-2.07) and total allergic rhinitis (aOR 1.67, 95% CI 1.17-2.37) between the ages of 6 and 48 months. The higher the trajectory of the maternal anxiety scores throughout pregnancy, the higher the odds of total eczema (aOR 1.65, 95% CI 1.14-2.40) and allergic rhinitis (aOR 1.84, 95% CI 1.28-2.66) in their offspring. The association between maternal anxiety and children's eczema was mainly concentrated in the first 24 months, whereas the association with allergic rhinitis was mainly concentrated in the 36-48 months. CONCLUSION: Maternal anxiety during any trimester of pregnancy, especially with a consistently high trajectory of anxiety scores, was associated with higher odds of children's eczema and allergic rhinitis.

Sex-Specific Associations between Maternal Thyroid Peroxidase Antibodies and Cognitive Development in Preschool Children: A Prospective Cohort Study.

Background: An association between maternal thyroid dysfunction throughout pregnancy and the subsequent risk of neurodevelopmental abnormalities in offspring has been demonstrated. However, the potential effects of maternal thyroid autoimmunity on neurodevelopment in the absence of maternal hypothyroidism remain unclear. Therefore, in this study, we explored the association between maternal thyroid peroxidase antibody (TPOAb) positivity and cognitive development in preschool children. Methods: A total of 1849 mother-child pairs were recruited from the Ma'anshan Birth Cohort (MABC) Study. During the follow-up period, an electrochemiluminescence immunoassay was used to retrospectively measure serum TPOAb levels in pregnant women. The cognitive development of preschool children was evaluated by using the Chinese version of the Wechsler Preschool and Primary Scale of Intelligence-Fourth Edition (WPPSI-IV). A growth mixture model was used to fit the trajectory of TPOAb. Multiple linear regression and logistic regression models were used to explore the associations between the developmental trajectory of TPOAb-positivity at different gestational periods and the cognitive development of preschool children by sex. Results: A total of 1849 mother-child pairs (mean [SD] age: 26.7 [3.6] years) were enrolled in the final study. Maternal TPOAb positivity in the first trimester was associated with a risk of below-average processing speed index in girls (OR: 2.07; 95% CI 1.06 to 4.01) and below-average full-scale intelligence quotient (FSIQ) in boys (OR: 2.36; 95% CI: 1.10 to 5.05). Maternal TPOAb positivity in the third trimester (T3) was associated with below-average working memory index (WMI) (OR: 2.51; 95% CI: 1.02 to 6.20) in girls. In girls, the WMI (ß = -3.17, 95% CI: -5.82 to -0.52), fluid reasoning index (FRI) (ß = -4.49, 95% CI: -7.18 to -1.80), and FSIQ score (ß = -2.43, 95% CI: -4.77 to -0.08) decreased, whereas in mothers, the level of log-transformed thyroid peroxidase antibody (lgTPOAb) increased during pregnancy. Conclusions: Positive maternal TPOAb levels during pregnancy may be associated with poorer cognitive development in preschool children. These findings require independent confirmation in other populations.

Interaction between isolated maternal hypothyroxinemia and pregnancy-related anxiety on preschooler's internalizing and externalizing problems: A birth cohort study.

BACKGROUND: Isolated maternal hypothyroxinemia (IMH) and pregnancy-related anxiety may increase the risk of offspring's emotional and behavioral problems, but little is known about their potential interactive effect on preschoolers' internalizing and externalizing problems. METHODS: We conducted a large prospective cohort study in Ma'anshan Maternal and Child Health Hospital between May 2013 and September 2014. There were a total of 1372 mother-child pairs from the Ma'anshan birth cohort (MABC) included in this study. IMH was defined as the thyroid-stimulating hormone (TSH) level within the normal reference range (2.5-97.5th percentile) and the free thyroxine (FT4) level below the 2.5th percentile, and negative TPOAb. The pregnancy-related anxiety questionnaire (PRAQ) was used to assess women's pregnancy-related anxiety status in the first (1-13 weeks), second (14-27 weeks) and third (after 28 weeks) trimesters of pregnancy. The Achenbach Child Behavior Checklist (CBCL/1.5-5) was used to assess preschoolers' internalizing and externalizing problems. RESULTS: Preschoolers born of mothers with IMH and anxiety had an increased risk of anxious/depressed (OR = 6.40, 95% CI 1.89-21.68), somatic complaints (OR = 2.69, 95% CI 1.01-7.20), attention problems (OR = 2.95, 95% CI 1.00-8.69) and total problems (OR = 3.40, 95% CI 1.60-7.21). Particularly, mothers with IMH and anxiety was associated with an increased risk of preschool girls' anxious/depressed (OR = 8.14, 95% CI 1.74-38.08), withdrawn (OR = 7.03, 95% CI 2.25-21.92), internalizing problems (OR = 2.66, 95% CI 1.00-7.08), and total problems (OR = 5.50, 95% CI 2.00-15.10). CONCLUSIONS: IMH and pregnancy-related anxiety during pregnancy may synergistically increase the risk of internalizing and externalizing problems in preschooler children. This interaction is distinct in internalizing problems of preschool girls.

Association of maternal thyroid peroxidase antibody during pregnancy with placental morphology and inflammatory and oxidative stress responses.

Background: Studies suggest that thyroid peroxidase antibody (TPOAb) positivity exposure during pregnancy may contribute to changes in placental morphology and pathophysiology. However, little is known about the association of maternal TPOAb during pregnancy with placental morphology and cytokines. This study focuses on the effect of repeated measurements of maternal TPOAb during pregnancy on the placental morphology and cytokines. Methods: Based on Ma'anshan Birth Cohort (MABC) in China, maternal TPOAb levels were retrospectively detected in the first, second and third trimesters. Placental tissues were collected 30 minutes after childbirth, placental morphological indicators were obtained by immediate measurement and formula calculation, and cytokine mRNA expression was detected by real-time quantitative polymerase chain reaction (RT-qPCR) afterward. Generalized linear models and linear mixed models were analyzed for the relationships of maternal TPOAb in the first, second and third trimesters with placental indicators. Results: Totally 2274 maternal-fetal pairs were included in the analysis of maternal TPOAb levels and placental morphology, and 2122 pairs were included in that of maternal TPOAb levels and placental cytokines. Maternal TPOAb levels in early pregnancy were negatively associated with placental length, thickness, volume, weight and disc eccentricity, while positively correlated with placental IL-6, TNF-α, CRP, CD68, MCP-1, IL-10, HO-1, HIF-1α and GRP78. In mid-pregnancy, maternal TPOAb levels were negatively correlated with placental length, width and area. In late pregnancy, maternal TPOAb levels were negatively correlated with placental length, area, volume and weight. Repeated measures analysis showed that maternal TPOAb positivity tended to increase placental TNF-α, CD68 and MCP-1 while decreasing placental length, width and area than TPOAb negativity. Repeated measures analysis showed that maternal TPOAb levels were positively correlated with placental IL-6, TNF-α, CD68, MCP-1, IL-10, HO-1, HIF-1α and GRP78, while negatively correlated with placental length, area, volume, weight, and disc eccentricity. Conclusion: There may be trimester-specific associations between maternal TPOAb levels and placental morphology and inflammatory and oxidative stress responses. The effect of maternal TPOAb levels on placental morphology is present throughout pregnancy. Early pregnancy may be the critical period for the association between maternal TPOAb levels and placental inflammatory and oxidative stress responses.

Association of Maternal TSH, FT4 With Children's BMI Trajectories, and Obesity: A Birth Cohort Study.

OBJECTIVE: To investigate the association between maternal TSH, free thyroxine (FT4), and children's body mass index (BMI) trajectories and obesity. METHOD: Based on the Ma'anshan Birth Cohort in China, we repeatedly assayed maternal thyroid functions in 3 trimesters of pregnancy. Children's height and weight were measured 15 times before they were age 6 years. Body fat was assessed when children were aged 6 years. Mplus software was used to fit maternal thyroid hormone trajectories and BMI trajectories. Multivariate logistic regression models and generalized linear models were used in data analysis. RESULTS: Low maternal FT4 trajectory was observed to be related to an increased risk of a high children's BMI trajectory and overweight, with an odds ratio and 95% CI of 1.580 (1.169-2.135) and 1.505 (1.064-2.129), respectively. Increased maternal FT4 concentrations in the first, second, and third trimesters were associated with a decreased risk of high children's BMI trajectories and obesity. There was a positive association between low maternal FT4 trajectory and 6-year-old children's body fat ratio with ß and 95% CI of 0.983 (0.138-1.829). Furthermore, negative correlations between maternal FT4 concentration in the first, second, and third trimesters of pregnancy and body fat ratio were observed. CONCLUSIONS: Low maternal FT4 trajectory during pregnancy may predict a high BMI trajectory in children and relate to overweight and high body fat ratio in 6-year-old children. High maternal FT4 concentrations throughout pregnancy may be associated with the decreasing risk of obesity and low body fat ratio in 6-year-old children.

Maternal anxiety during pregnancy and children's asthma in preschool age: The Ma'anshan birth cohort study.

BACKGROUND: The fetal immune system and consequent elevated risk of asthma in childhood may be impacted by maternal anxiety during pregnancy. Limited studies have evaluated whether there was a sensitive period and cumulative effect of the relationship between prenatal anxiety and children's asthma. METHODS: 3131 mother-child pairs made up the study's sample from the Ma'anshan Birth Cohort Study in China. Maternal anxiety status was repeated three times using the pregnancy-related anxiety questionnaire in the 1st, 2nd and 3rd trimesters of pregnancy. Diagnostic information on asthma was collected three times at 24, 36, and 48 months of age. RESULTS: After adjusting for confounders, children born to mothers with anxiety in the 1st, 2nd and 3rd trimesters of pregnancy all had an elevated risk of total asthma from 12 to 48 months of age. After further adjusting prenatal anxiety in the other trimesters, no association was observed between prenatal anxiety in any trimester and preschoolers' asthma. Children of mothers with persistently high anxiety score trajectory during pregnancy had an elevated risk of total asthma and high prevalence trajectory of asthma. Cumulative effects analysis showed that the more frequent the mother's anxiety, the higher the risk of her offspring developing a high prevalence trajectory of asthma from 12 to 48 months of age. The results of the subgroup analysis by age showed similar associations overall. CONCLUSIONS: Maternal antenatal anxiety was associated with an elevated risk of preschool children's asthma, and a possible cumulative effect was observed. Maternal mental health conditions during pregnancy should receive constant attention throughout pregnancy, not just during one period.

Maternal pre-pregnancy body mass index, gestational weight gain, and pubertal timing in daughters: A systematic review and meta-analysis of cohort studies.

The timing of daughter's puberty onset is constantly earlier. It is still unclear about the maternal pre-pregnancy body mass index (BMI) and gestational weight gain (GWG) as important prenatal factors that may affect offspring's onset of puberty. Thus, we evaluated the association among maternal pre-pregnancy BMI, GWG, and daughters' early pubertal development based on the existing literature. Literature review was conducted in different databases, including Web of Science, Pubmed, Wiley, ScienceDirect, Web of Science, and Chinese National Knowledge Infrastructure databases up to June 2021. We selected random effects model or fixed effects model for meta-analysis according to the I2 statistics value to obtain the summary measurement. A total of 12 cohort studies were included. Compared to maternal pre-pregnancy normal weight, maternal pre-pregnancy overall overweight/obesity (RR = 1.24; 95% CI 1.17 to 1.32), obesity (RR = 1.35; 95% CI 1.23 to 1.48), and overweight (RR = 1.17; 95% CI 1.09 to 1.26) were significantly associated with the increased risk of earlier timing of pubertal onset in daughters. Daughters born of mothers with pre-pregnancy overall overweight/obesity, obesity, and overweight had earlier pubertal onset compared to those born of mothers with normal weight ([mean difference = -3.03, 95% CI: -3.97 to -2.10], [mean difference = -3.50, 95% CI: -5.38 to -1.62], and [mean difference = -2.89, 95% CI: -4.07 to -1.71], respectively). The effects were also significant in the assessed three milestones (menarche, breast development, and pubic hair development). Maternal excessive GWG increased the risk of early pubertal timing in daughters (RR = 1.19; 95% CI 1.09 to 1.30).

Sex-specific Effect of Maternal Thyroid Hormone Trajectories on Preschoolers' Behavioral Development: A Birth Cohort Study.

CONTEXT: Maternal thyroid hormone trajectories are a better predictor of offspring's neurodevelopment than hormone levels in single trimester of pregnancy. Programming effect of uterine hormonal environment on offspring's health is usually sex-specific. OBJECTIVE: To examine the sex-specific effect of thyroid hormone trajectories on preschoolers' behavioral development. DESIGN: Based on Ma' anshan Birth Cohort in China, pregnant women were recruited at their first antenatal checkup from May 2013 to September 2014. SETTING: Ma' anshan Maternal and Child Health Hospital in China. PATIENTS OR OTHER PARTICIPANTS: 1860 mother-child pairs were included in the analysis. Children were followed up at age of 4. MAIN OUTCOME MEASURES: Maternal thyroid hormones [thyroid-stimulating hormone (TSH), free thyroxine (FT4)] and thyroid peroxidase antibody in the first, second, and third trimesters of pregnancy were retrospectively assayed. Preschoolers' behavioral development was assessed by Achenbach Child Behavior Checklist/1.5~5. RESULTS: Maternal TSH and FT4 levels were respectively fitted into high, moderate, and low trajectories. In boys, maternal high TSH trajectory was related to withdrawn [odds ratio (OR) = 2.01, 95% CI: 1.16, 3.50) and externalizing problems (OR = 2.69, 95% CI: 1.22, 5.92), and moderate TSH trajectory was associated with aggressive behavior (OR = 3.76, 95% CI: 1.16, 12.23). Maternal high FT4 trajectory was associated with anxious/depressed (OR = 2.22, 95% CI: 1.08, 4.56) and total problems (OR = 1.74, 95% CI: 1.13, 2.66), and low FT4 trajectory was associated with aggressive behavior (OR = 4.17, 95% CI: 1.22, 14.24). CONCLUSIONS: Maternal thyroid hormone trajectories impact preschool boys' behavioral development.

Sex-Specific Effect of Thyroid Peroxidase Antibody and Thyroglobulin Antibody Exposure During Pregnancy on Preschoolers' Emotional and Behavioral Development: A Birth Cohort Study.

Background: Epidemiological and experimental studies suggest that thyroid peroxidase antibody (TPOAb)- and thyroglobulin antibody (TGAb)-positive exposure during gestation may contribute to offspring's adverse neural development. However, limited knowledge is available on the association between joint exposure on TPOAb and TGAb and children's emotional and behavioral development. Furthermore, the sex-specific effect on the developmental process of preschoolers' emotions and behaviors is unknown. The present research intends to examine the sex-specific effect of TPOAb- and TGAb-positive exposure in gestation on the developmental process of preschoolers' emotions and behaviors. Methods: A total of 2455 mother-child pairs were included from the Ma'anshan Birth Cohort study. The serum TPOAb and TGAb of pregnant women was measured retrospectively by electrochemical immunoassay during the follow-up period. Preschoolers' emotional and behavioral development was assessed by a child behavior checklist 1.5-5. Growth mixture modeling was adopted to fit thyroid antibody (TAb) trajectories. Poisson regression models were used, stratifying by sex, to examine the association between TAb trajectories, as well as four categories of maternal TAb exposure and preschoolers' emotional and behavioral problems. Results: Boys born to mothers with TPOAb positivity in the first, second, and third trimesters of pregnancy had an increased risk of autism spectrum problems after adjusting for confounders, with relative risk (RR) [confidence interval, CI] of 2.01 [1.24-3.27], 2.15 [1.08-4.26], and 2.13 [1.20-3.79], respectively. Maternal TGAb positivity and TPOAb negativity in the first trimester were associated with a high risk of attention-deficit/hyperactivity problems in boys (RR = 1.74 [CI 1.01-2.99]). The prevalence of depressive problems in girls was 33.3% after exposure to TPOAb alone in the third trimester of pregnancy. Exposure to TPOAb alone in the third trimester of pregnancy was associated with an increased risk of depressive problems in girls (RR = 1.78 [CI 1.09-2.90]). Conclusions: Maternal TPOAb positivity in all three trimesters was associated with the risk of autism spectrum problems in boys. Isolated maternal TGAb positivity in the first trimester was associated with attention-deficit/hyperactivity problems in boys, whereas isolated maternal TPOAb positivity in the third trimester was associated with depressive problems in girls.

Sarcopenia May Be a Risk Factor for Osteoporosis in Chinese Patients with Rheumatoid Arthritis.

PURPOSE: Osteoporosis (OP) has been classically considered a co-morbidity of rheumatoid arthritis (RA). This investigation determined the clinical significance of sarcopenia in patients with RA combined with OP or whether sarcopenia influences RA when combined with OP. MATERIALS AND METHODS: Data pertaining to the duration of RA, C-reactive protein (CRP) level, and erythrocyte sedimentation rate (ESR) were collected from 549 RA cases and 158 healthy individuals. Disease activity score at 28 joints (DAS28), the body mass index (BMI), health assessment questionnaire (HAQ), bone mineral density (BMD), and Sharp score were compared between the 2 groups. RESULTS: The prevalence of OP (33.3% vs 12.7%, χ 2= 69.992, P < 0.0001) and sarcopenia (61.7% vs 9.0%, χ 2= 135.336, P < 0.01) was greater in patients with RA than in healthy controls. RA patients with sarcopenia had a higher incidence of OP at all measured sites than RA patients without sarcopenia (all P < 0.0001), and the incidence of OP was significantly higher than in patients with mild-to-moderate or severe RA without sarcopenia (P < 0.0001). Differences in age, gender, course of disease, CRP level, ESR, DAS28, BMI, HAQ, BMD, and Sharp score were statistically different between the RA with or without sarcopenia groups (P < 0.01). The incidence of OP and sarcopenia was higher in RA patients treated than not treated with glucocorticoids [GCs] (36.4% vs 29.3%, P < 0.05 and 66.1% vs 56.0%, respectively; P < 0.05). Logistic regression showed that the risk factors for OP in RA individuals were female (OR, 14.671; 95% CI, 6.877-31.300; P < 0.0001), age (OR, 1.100; 95% CI, 1.076-1.124; P < 0.0001), and sarcopenia (OR, 3.561; 95% CI, 2.214-5.726; P < 0.0001). CONCLUSION: OP and sarcopenia are common in RA patients. Sarcopenia may be a risk factor for OP occurrence in Chinese patients with RA.

Interactive effect of sarcopenia and falls on vertebral osteoporotic fracture in patients with rheumatoid arthritis.

Patients with rheumatoid arthritis (RA) had higher incidences of sarcopenia, falls, osteoporosis, and vertebral osteoporotic fractures (VOPF). Sarcopenia was associated with longer disease duration, higher disease activity, and more severe RA. The interactive effect of sarcopenia and falls was associated with a higher risk of VOPF in patients with RA. PURPOSE: Whether sarcopenia and falls are a risk factor for vertebral fracture in RA patients has not been demonstrated. This study aimed to explore the incidence of vertebral osteoporotic fracture (VOPF) and its relationship with sarcopenia and falls in RA patients. METHODS: A total of 474 RA patients and 156 controls were enrolled in this study. Anteroposterior and lateral X-ray examinations of the vertebral column (T4-L4) were used for the semiquantitative assessment of VOPF. Bone mineral density was measured by dual-energy X-ray absorptiometry. Skeletal muscle mass was measured by direct segmental multifrequency bioelectrical impedance analysis (DSM-BIA method). RESULTS: RA patients had an increased risk of sarcopenia (62.4% vs 9.0%, x2 = 47.478, P < 0.001), falls (30.2% vs 3.2%), osteoporosis (OP) (33.5% vs 12.8%, x2 = 134.276, P < 0.001), and VOPF (20.3% vs 3.8%, x2 = 47.478, P < 0.001) than controls. Patients with sarcopenia were more likely to have VOPF than RA without sarcopenia (24.0% vs 14.0%, x2 = 6.802, P = 0.009). RA with sarcopenia and prior falls had the highest incidences of VOPF (36.7%). Older age (OR = 1.056, P < 0.001, 95% CI 1.030-1.083), falls (OR = 2.043, P = 0.003, 95% CI 1.238-3.371), OP (OR = 1.819, P = 0.034, 95% CI 1.046-3.163), and usage of glucocorticoids (GCs) (OR = 1.862, P = 0.022, 95% CI 1.093-3.172) were risk factors for VOPF in RA patients, while a higher skeletal muscle index (SMI) was a protective factor (OR = 0.754, P = 0.038, 95% CI 0.578-0.984) for VOPF in RA patients. CONCLUSIONS: The interactive effect of sarcopenia and falls is associated with a higher risk of VOPF in patients with RA.