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

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

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

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

No role of the third-trimester inflammatory factors in the association of gestational diabetes mellitus with postpartum cardiometabolic indicators.

BACKGROUND: The influence of gestational diabetes mellitus (GDM) on postpartum cardiometabolic indicators is primarily restricted to glucose and lipid metabolism, however the indicators for liver and kidney function have been rarely explored, and the role of the third-trimester inflammatory factors in these associations has never been investigated. METHODS: Based on the Ma'anshan birth cohort (MABC), women with or without GDM history were selected and invited to participate in a 6-year postpartum follow-up. The fasting blood samples were collected to measure 16 comprehensive metabolic indicators during a 6-year postpartum follow-up: fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1c), triglycerides (TG), total cholesterol (TC), uric acid (UA), blood urea nitrogen (BUN), serum creatinine (SCR), etc. Seven inflammatory factors, including TNF-α, IFN-γ, IL-1ß, IL-6, IL-10, IL-12p70, and IL-17 A, were measured with serum samples collected during the third trimester of pregnancy. Linear regression models were used to analyze the associations between GDM and 6-year postpartum metabolic indicators, GDM and third-trimester inflammatory factors, and the third-trimester inflammatory factors and 6-year postpartum metabolic indicators. Mediating and moderating effect analyses were further performed to explore if the third-trimester inflammatory factors mediate or modify the association between GDM and postpartum cardiometabolic indicators. RESULTS: From July 2021 to August 2022, 307 participants have been followed up, with 99 women with a prior GDM history. Compared with those without GDM, individuals with a prior history of GDM had significantly elevated levels of FPG (ß = 0.40, 95% CI: 0.18 to 0.62, PFDR < 0.001), HbA1c (ß = 0.22, 95% CI: 0.09 to 0.34, PFDR = 0.009), TyG (ß = 0.22, 95% CI: 0.07 to 0.37, PFDR = 0.024) at 6 years postpartum, and the association between GDM and SCR (ß = 2.43, 95% CI: 0.02 to 4.85, PFDR = 0.144) reached nominal significance level. GDM history was associated with a decreased level of third-trimester IL-17 A (ß = -0.58, 95% CI: -0.99 to -0.18, PFDR = 0.035). No significant association between third-trimester inflammatory factors and 6-year postpartum metabolic indicators was observed. And no mediating or moderating effect of third-trimester inflammatory factors was observed in those associations. CONCLUSION: A prior history of GDM was significantly associated with elevated FPG, HbA1c, and TyG in women at 6 years postpartum, whereas third-trimester inflammatory factors had no role in mediating or moderating these associations.

Sex-specific association between maternal mild anemia and children's behavioral development: a birth cohort study.

There has been limited research on maternal anemia affecting children's behavioral development, with a lack of studies focusing on sex differences in this association. Based on the Ma'anshan Birth Cohort, 2132 mother-child pairs were included. Maternal anemia was evaluated based on the hemoglobin concentration and children's behavioral development was assessed by Achenbach Child Behavior Checklist 1.5-5. Binary logistic regression models indicated that compared with children born of mothers without anemia throughout pregnancy, maternal mild anemia during pregnancy or only anemia in the 3rd trimester was associated with increased risks of aggressive behaviors in boys. Maternal mild anemia only in the 2nd trimester was associated with increased risks of attention problems in boys. In girls, maternal mild anemia during pregnancy was associated with increased risks of withdrawn, internalizing problems and total problems. Girls born of mothers with mild anemia only in the 2nd trimester had higher risks of total problems. Maternal mild anemia in both 2nd and 3rd trimesters was associated with increased risks of internalizing problems in girls. Our study identified sex-specific effects of maternal mild anemia during pregnancy on children's behavioral development problems.

Psychometric soundness and predictive factors of the NCAST Parent-Child Interaction Teaching Scale in urban Chinese population.

BACKGROUND: Quality of parent-child interaction in early childhood functions as a critical indicator of nurturing care and is strongly associated with short-term and long-term development (health, cognition, language, social emotion, well-being, etc.). NCAST PCI Teaching Scale (PCI-TS), a video-based assessment regarded as a gold standard to measure PCI, has been widely used worldwide. However, its psychometric soundness among the urban Chinese population is unclear. This study assesses the PCI-TS's reliability and validity and explores predictive factors among urban Chinese parent-child dyads. METHODS: PCI-TS was adopted to code mother-child interaction among urban Chinese dyads recruited during the children's regular health checks in local maternal and child health centres. Reliability was evaluated by internal consistency (Cronbach'α coefficient) and test-retest reliability (Pearson correlation) with an average interval of 18 days. Score distribution of each subscale and total scale were compared with NCAST Database and Canadian community sample by single sample t-test. Criteria-related validity was conducted by Infant-Toddler Home Observation Measurement of the Environment (Pearson correlation). Predictive factors was performed by multiple linear regression. RESULTS: Four hundred and twenty-nine eligible mother-child dyads were included for data analysis among the 466 recruited samples. Four qualified local paediatricians accomplished video coding with an average agreement of 86%. The PCI-TS has strong reliability among the Chinese population with the Cronbach'α coefficients of the Caregiver-Infant total score, Caregiver total and Infant total scores of 0.81, 0.81 and 0.74, respectively; an acceptable test-retest reliability (r = 0.73, p < 0.01); and moderate correlation with IT-HOME, ranging from 0.53 to 0.62. Child age, birth weight, maternal education, full-time housewife, living with grandparent(s) and living space were predictive factors on PCI-TS in the Chinese population. CONCLUSION: PCI-TS showed good psychometric properties for measuring mother-child interactions among urban Chinese dyads, offering clinicians and researchers a practical tool to evaluate PCI objectively. Child age, maternal education and living space were beneficial factors, while full-time mothers and living with grandparent(s) were risk factors.

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.

Association between prenatal metals exposure and blood pressure in 5-6 years children: A birth cohort study.

BACKGROUND: The trajectory of blood pressure (BP) from childhood to early middle age suggested that individuals with elevated BP in early childhood were more likely to be affected by cardiovascular disease in adulthood. Exposure to metals may affect BP in children, and pregnancy is a sensitive time for metal exposure. This study assessed the relationship between different stages of prenatal exposure to metals or metal mixtures and BP in children aged 5-6 years. METHODS: The study included 2535, 2680, 2534 mother-child pairs in three trimesters, from the Ma'anshan birth cohort study (MABC). We collected maternal blood samples during pregnancy and measured the serum levels of four metals (arsenic, selenium, cadmium, and mercury). BP was measured in children aged 5-6 years. A linear regression model and Bayesian kernel machine regression (BKMR) were used to explore associations between prenatal exposure to metals at different stages and multiple metal exposure with BP in children aged 5-6 years. RESULTS: Associations were observed between the arsenic in the third trimester and children's diastolic blood pressure (DBP) (ß = 0.88, 95% CI: 0.44, 1.33), systolic blood pressure (SBP) (ß = 0.72, 95% CI: 0.19, 1.24) and mean arterial pressure (MAP) (ß = 0.83, 95% CI: 0.42, 1.23), as well as between the mercury and children's DBP (ß = 0.65, 95% CI: 0.13, 1.16) and MAP (ß = 0.60, 95% CI: 0.14, 1.07). The BKMR analysis showed that multiple metals had a significant positive joint effect on children's DBP, SBP and MAP. A potential interaction between arsenic and mercury was observed (ß = -0.85, 95% CI: -1.62, -0.08). CONCLUSIONS: Exposure to arsenic and mercury during pregnancy was associated with altered BP in children. The third trimester may represent an important window of opportunity to reduce the effects of metal exposure on children's blood pressure and long-term health.

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.

The associations of gestational weight gain and midpregnancy lipid levels with placental size and placental-to-birth weight ratio: findings from a chinese birth cohort study.

BACKGROUND: The placenta serves as the sole maternal organ responsible for transmitting nutrients to the fetus, playing a crucial role in supporting standard fetal growth and development. To date, only a small number of studies have investigated the impact of maternal gestational weight gain and lipid concentrations on placental development. This study aimed to explore the influence of weight gain during pregnancy and lipid levels in the second trimester on placental weight, volume, and the placental weight ratio. METHODS: This birth cohort study encompassed 1,358 mother-child pairs. Placental data for each participant was gathered immediately post-delivery, and the study incorporated data on gestational weight gain throughout pregnancy and lipid profiles from the mid-trimester. A linear regression model was employed to assess the correlations between gestational weight gain, mid-trimester lipid levels, and metrics such as placental weight, placental volume, and the placental-to-birth weight ratio (PFR). RESULTS: In the study groups of pre-pregnancy underweight, normal weight, and overweight, the placental weight increased by 4.93 g (95% CI: 1.04-8.81), 2.52 g (95% CI: 1.04-3.99), and 3.30 g (95% CI: 0.38-6.22) per 1 kg of gestational weight gain, respectively. Within the pre-pregnancy underweight and normal weight groups, the placental volume increased by 6.79 cm^3 (95% CI: 3.43-10.15) and 2.85 cm^3 (95% CI: 1.31-4.39) per 1 kg of gestational weight gain, respectively. Additionally, placental weight exhibited a positive correlation with triglyceride (TG) levels (ß = 9.81, 95% CI: 3.28-16.34) and a negative correlation with high-density lipoprotein (HDL-C) levels (ß = - 46.30, 95% CI: - 69.49 to - 23.11). Placental volume also showed a positive association with TG levels (ß = 14.54, 95% CI: 7.69-21.39). Conversely, PFR demonstrated a negative correlation with increasing HDL-C levels (ß = - 0.89, 95% CI: - 1.50 to - 0.27). CONCLUSIONS: Gestational weight gain was significantly correlated with both placental weight and volume. This association was especially pronounced in women who, prior to pregnancy, were underweight or of normal weight. Additionally, TG and HDL-C levels during the mid-trimester were linked to placental development.

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.

Comparison of mothers' perceptions of hunger cues in 3-month-old infant under different feeding methods.

BACKGROUND: Mothers' perception of infant hunger cues is a critical content of responsive feeding, which is central to the promotion of early childhood development. However, only a few studies have examined responsive feeding in China, especially lacking the studies on perceptions of infant hunger cues. Consider the cultural differences, the aim of this study was to describe the perceptions of infant hunger cues of Chinese mothers for infants aged 3 months, and explore the relationship between maternal perceptions of infant hunger cues and different feeding methods. METHODS: A cross-sectional study was conducted with a sample of 326 mothers of healthy 3-month-old infants, including 188 exclusive breastfeeding (EBF) mothers and 138 formula feeding (FF) mothers. It was implemented in four provincial and municipal maternal and child health hospitals. The mothers' perceptions of infant hunger cues were surveyed by self-reporting questionnaires. Chi-square tests and logistic analysis were applied to analyze the differences in maternal perceptions of infant hunger cues, including the number of hunger cues and the specific cues, between EBF group and FF group by controlling sociodemographic variables and the daily nursing indicators. RESULTS: We found that a higher proportion of EBF mothers could perceive multiple hunger cues (≥ 2) than FF mothers (66.5% vs.55.1%). For specific cues, the EBF mothers had higher perceptions of infant's "hand sucking" (67.6% vs. 53.6%) and "moving head frantically from side to side" (34.6% vs. 23.9%), all p < 0.05. Regression analysis revealed that EBF might support mothers to perceive infant hunger cues than FF mothers, with the number of infant hunger cues (OR = 1.70, 95% CI: 1.01-2.85), "hand sucking" (OR = 1.72, 95% CI: 1.04-2.87), "moving head frantically from side to side" (OR = 2.07, 95% CI: 1.19-3.62). The number of infant hunger cues perceived by mothers was also associated with their educational level and family structure. CONCLUSION: EBF mothers of 3-month-old infants may be more likely to perceive infant hunger cues than FF mothers in China. It is necessary to increase the health education about infant hunger and satiety cues to caregivers in China, especially among mothers with lower education levels, mothers living in nuclear families, and FF mothers.

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.

Gender-specific associations of pregnancy-related anxiety with placental epigenetic patterning of glucocorticoid response genes and preschooler's emotional symptoms and hyperactivity.

BACKGROUD: We have recently reported that maternal prenatal pregnancy-related anxiety predicts preschoolers' emotional and behavioral development in a gender-dependent manner. This study aims to test for this gender-specific effect in a different cohort and investigate whether the gender difference was specific to placental methylation of genes regulating glucocorticoids. METHODS: A total of 2405 mother-child pairs from the Ma'anshan Birth Cohort Study were included in present study. The maternal pregnancy-related anxiety symptoms were evaluated with the Pregnancy-Related Anxiety Questionnaire in the third trimester of pregnancy. Child neurobehavior was assessed with the Strengths and Difficulties Questionnaire at 4 years old. Placental methylation of FKBP5, NR3C1 and HSD11B2 genes was quantified using the MethylTarget approach in 439 pregnant women. After exploratory factor analysis, the associations between methylation factor scores and pregnancy-related anxiety and child neurobehavior were examined using logistic regression analysis. RESULTS: After controlling for confounding factors, pregnancy-related anxiety in the third trimester of pregnancy increased the risk of hyperactivity only in boys and emotional symptoms only in girls. Decreased scores of the factor characterized by FKBP5 methylation were associated with maternal pregnancy-related anxiety only in boys. Furthermore, increased scores of the factors characterized by NR3C1 and HSD11B2 methylation were associated with hyperactivity (NR3C1: adjusted OR = 1.80, 95%CI = 1.15-2.83) and emotional symptoms (HSD11B2: adjusted OR = 0.53, 95%CI = 0.29-0.97; NR3C1: adjusted OR = 1.64, 95%CI = 1.03-2.59) only in boys. However, the scores of the factor characterized by FKBP5, NR3C1 and HSD11B2 did not mediate the relationship between maternal pregnancy-related anxiety and preschoolers' emotional symptoms and hyperactivity. CONCLUSIONS: Our results suggested that pregnancy-related anxiety in the third trimester of pregnancy predicted preschoolers' emotional symptoms and hyperactivity in a gender-dependent manner. Although we did not find the mediation role of the placental methylation of genes regulating glucocorticoids, we found it was associated with both maternal pregnancy-related anxiety and preschoolers' emotional symptoms and hyperactivity in a gender-dependent manner.

Prenatal low-dose antibiotic exposure and children allergic diseases at 4 years of age: A prospective birth cohort study.

BACKGROUND: Based on a medical record or questionnaire survey approach, previous epidemiological studies have investigated associations between maternal antibiotic exposure during pregnancy and childhood allergic diseases. However, biomonitoring studies on the prenatal low-dose antibiotic exposure, mainly from the environment and contaminated food, and in relation to children allergic diseases, are missing. OBJECTIVES: This research aimed to examine the associations between prenatal low-dose antibiotic exposure measured at multiple time points and children current allergic diseases at 4 years of age. METHODS: The current study including 2453 mother-child pairs was based on the Ma'anshan Birth Cohort study. Selected 41 antibiotics and their two metabolites, which including human antibiotics (HAs), preferred as human antibiotics (PHAs), veterinary antibiotics (VAs) and preferred as veterinary antibiotics (PVAs), in urine samples from 2453 pregnant women were biomonitored through liquid chromatography-triple quadrupole tandem mass spectrometry. Information on children current allergic diseases were collected via validated questionnaires. Generalized estimating equation were used to explore the associations between the repeated measurements of maternal urinary antibiotic over three trimesters and current allergic diseases in children. RESULTS: The detection rates of nine individual antibiotics in the three trimester during pregnancy are greater than 10%, and the 90th percentile concentration of the detected antibiotics ranges from 0.07 to 22.34 µg/g, and the 95th percentile concentration ranges from 0.17 to 59.57 µg/g. Among the participants, each one-unit concentration increment of sulfamethazine (adjusted OR=1.28, 95% CI: 1.10, 1.49, P-FDR=0.014) in the first trimester and ciprofloxacin (adjusted OR=1.17, 95% CI: 1.07, 1.28, P-FDR=0.008) in the second trimester were associated with an increased risk of current eczema in children. In the third trimester, each one-unit concentration increment of oxytetracycline (adjusted OR=1.90, 95% CI: 1.30, 2.78, P-FDR=0.014) was associated with an increased risk of current asthma in children. Gender-stratified analyses demonstrated that no gender differences were observed in the associations between prenatal antibiotic exposure and current allergic diseases in children. CONCLUSIONS: Maternal exposure to certain specific VAs or PVAs (sulfamethazine, ciprofloxacin and oxytetracycline) in different trimesters was associated with an increased risk of current asthma and current eczema in 4-year-old children. No gender differences were found in these associations. Further studies are warranted to confirm our findings and explore the potential mechanisms.

Early childhood screen time as a predictor of emotional and behavioral problems in children at 4 years: a birth cohort study in China.

BACKGROUND: Previous studies have suggested that screen time (ST) has a negative effect on children's emotional and behavioral health, but there are few longitudinal studies that have been conducted with infants and toddlers. This study sought to examine the effect of ST in early childhood on emotional and behavioral problems in children aged 4 years, based on a birth cohort study in China. METHODS: A total of 2492 children aged 4 years were enrolled in this study. The parents and guardians of each child completed a questionnaire that included items eliciting information on children's birth information, socio-demographic information at baseline, and ST at each follow-up. Emotional and behavioral problems were assessed using the Strengths and Difficulties Questionnaire (SDQ) at 4 years of age. Multivariate logistic analysis was used to explore the effects of ST on emotional and behavioral problems. RESULTS: The percentages of children with ST > 0 h/day at age 0.5 years, ST > 2 h/day at age 2.5 years, and ST > 2 h/day at age 4 years were 45.7, 55.5, and 34.5% respectively. The prevalence of emotional and behavioral problems was 10.8%. ST at 6 months was a risk factor for emotional symptoms and hyperactivity at the age of 4 years. ST at age 2.5 years was a risk factor for hyperactivity at the age of 4 years. However, ST at age 4 years was a risk factor for total difficulties, conduct problems, peer problems, hyperactivity, and prosocial behavior. CONCLUSIONS: Higher ST exposure at early childhood is associated with later emotional and behavioral problems. In particular, sustained high ST exposure is a risk factor for behavioral problems. These findings suggested the importance of controlling ST to prevent the occurrence of emotional and behavioral problems in the early years.

Elective caesarean section on maternal request prior to 39 gestational weeks and childhood psychopathology: a birth cohort study in China.

BACKGROUND: The recommendation of non-indicated caesarean section (CS) after 39 gestational weeks has been announced based on evidence of maternal and infant physiological effects. The potential psychological risks have not been acknowledged. This study aims to investigate emotional and behavioral problems in pre-school children born with elective CS (ECS) on maternal request prior to 39 weeks. METHODS: Pregnant women within 12 gestational weeks between November 2008 and October 2010 were invited to participate in the China-Anhui Birth Cohort Study (C-ABCS). They were asked to complete a self-administered questionnaire respectively in 1st and 3rd trimester of pregnancy to collect basic maternal characteristics. Pregnant complications and delivery modes were abstracted from medical notes. Their singleton live births were followed up at preschool age. Strengths and Difficulties Questionnaires (SDQ) were completed by parents to assess children's emotional and behavioral problems. A total of 3319 mother-child pairs were put into the final analysis. Descriptive analysis and binary logistic regression analysis were used to assess the impact of delivery modes on abnormalities in SDQ dimensions at various gestational ages. RESULTS: The prevalence of ECS on maternal request prior to 39 weeks, at 39-40 weeks, and after 41 weeks was 16.6, 23.7 and 15.9%, respectively. Compared with those born vaginally, children born with ECS on maternal request were more likely to have total difficult problems (RR 1.519, 95% confidence interval 1.077 to 2.142). ECS on maternal request was the independent predictor of emotional problems (3.479, 1.676 to 7.222) and total difficult problems (2.172, 1.175 to 4.016) in children born prior to 39 gestational weeks. CONCLUSION: Children delivered by ECS on maternal request have an increased risk to have emotional and behavioral problems prior to 39 gestational weeks at preschool age. The potential psychological implication prior to 39 weeks has been added to the roster of impacts of ECS on maternal request. Further research is needed to probe the potential biological mechanisms.

Isolated effect of maternal thyroid-stimulating hormone, free thyroxine and antithyroid peroxidase antibodies in early pregnancy on gestational diabetes mellitus: a birth cohort study in China.

This article aims to understand the isolated effect of maternal thyroid-stimulating hormone (TSH), free thyroxine (FT4) and antithyroid peroxidase antibodies (TPOAb) in early pregnancy on gestational diabetes mellitus (GDM). Based on a birth cohort, pregnant women presented to maternity hospitals for the first antenatal care from Nov 2008 to Oct 2010 were invited to participate in the study. A self-administered questionnaire was asked to complete to collect data on socio-economic variables, previous adverse pregnancy outcomes, method of conception, previous endocrinic and metabolic diseases, and pregnancy-related anxiety in 1st trimester of the index pregnancy. Pre-pregnancy BMI was measured. Serum samples were collected, and TSH, FT4 and TPOAb were assayed. GDM was confirmed from medical records screened on 24-28 gestational weeks by using oral glucose tolerance test (OGTT). The prevalence of isolated subclinical hypothyroidism, hypothyroidemia and positive TPOAb in early pregnancy was 2.0%, 2.0% and 12.8%. Prevalence of GDM in women with the isolated sub-clinical hypothyroidism, hypothyroxinemia and positive TPOAb was 2.9%, 2.8% and 3.1%, respectively, which were all higher than that detected in euthyroidism women (1.2%). Women with isolated positive TPOAb had significantly higher TSH and lower FT4 level compared with euthyroidism women. It was found that isolated positive TPOAb in early pregnancy increased the risk of GDM, adjusted RR and 95%CI being 2.541(1.037-6.226). No significant relationships were identified between isolated sub-clinical hypothyroidism or hypothyroxinemia with GDM. In conclusion, isolated thyroid autoimmunity, represented by positive TPOAb, in early pregnancy were associated with GDM independent of TSH and FT4.

Associations of grandparental diabetes mellitus with grandchild BMI status.

BACKGROUND: Maternal family history of diabetes was significantly and positively associated with birth weight in grandchildren, we aim to assess the effect of grandparental diabetes on the grandchild' body mass index (BMI) at infancy peak (IP) and obesity status at age 2. METHODS: In our study, family diabetes mellitus (DM) information from Ma'anshan Birth Cohort Study (MABC) were gathered. For children, height and weight were retrieved from medical records. BMI at 6 observations (0, 3, 6, 9, 12, 18 months) was plotted for every child. Onset of IP was determined by visual inspection. BMI at age 2 was categorized according to WHO Child Growth Standards as normal, overweight or obesity. The association between maternal grandfather' diabetes and the grandchild' BMI at IP and BMI at age 2 were tested using linear regression models and logistic regression models, respectively. RESULTS: In our sample, about 6% of the maternal grandfather had DM, mean of infancy BMI peak was 18.37 kg/m2, and 6.6% of the children were obesity at age 2. Maternal grandfather with DM could significantly increase the IP BMI values (ß = 0.30, 95 CI = 0.02~0.57), and was associated with obesity status at age 2 (OR = 1.92, 95 CI = 1.08~3.39), but maternal grandmother and paternal grandparents were unrelated. CONCLUSION: These results suggest that DM in maternal grandfather may be a risk factor for the grandchild high BMI at peak and obesity at age 2.

Using epidemiological data to identify needs for child-rearing support among Chinese parents: a cross-sectional survey of parents of children aged 6 to 35 months in 15 Chinese cities.

BACKGROUND: The quality of the family environment-in particular, the kind of parenting children receive in their early years-plays a critical role in influencing children's growth and development. To facilitate the development and delivery of appropriate parenting and family interventions for Chinese parents, this study explores the prevalence of the difficulties that may arise in the course of child-rearing, the associated sociodemographic factors and parents' help-seeking behavior. METHODS: A cross-sectional self-reporting survey was conducted with a sample of 2229 parents of children between 6 and 35 months of age. Using a stratified random-digit design, parents from 15 Chinese cities were surveyed to determine their child-rearing difficulties, support-seeking behavior and their preferences for service delivery. The sociodemographic factors that influenced major child-rearing difficulties were analyzed using bivariate and logistic analyses. RESULTS: The majority (87.5%) of Chinese parents of children aged 6-35 months reported experiencing child-rearing difficulties. Nearly one third (31.5%) of parents reported experiencing major difficulties. Feeding and sleep problems were most often reported. Regression analysis revealed that major child-rearing difficulties most often involved male children (OR = 1.35, 95% CI 1.11-1.64), single-child households (OR = 1.38, 95% CI 1.07-1.77), and households with financial problems (OR = 1.40, 95% CI 1.06-1.85). Just over one third of parents (33.44%) sought professional support, while 21.37% had attended a parenting course in the past year. Prefer ways of sourcing parental support included professional online platform (69.24%), self-help books (43.70%), face-to-face consultation (24.99%), and attending lectures (36.57%). CONCLUSIONS: Child-rearing difficulties are common among parents of children between 6 and 35 months of age in Chinese cities. The family with boys, single-child, financial problems, and father not joining in child-rearing may face the high risk to major child-rearing difficulties. The national initiative to provide more guidance and support for child-rearing difficulties is worthwhile, as is the development of online parenting programs.