Clinical and virological characteristics of coexistent hepatitis B surface antigen and antibody in treatment-naive children with chronic hepatitis B virus infection.

Serological pattern of simultaneous positivity for hepatitis B surface antigen (HBsAg) and antibody against HBsAg (anti-HBs) is considered a specific and atypical phenomenon among patients with chronic hepatitis B virus (HBV) infection, especially in pediatric patients. Unfortunately, there is limited understanding of the clinical and virological characteristics among children having chronic HBV infection and the coexistence of HBsAg and anti-HBs. Hence, our objective was to determine the prevalence of coexistent HBsAg and anti-HBs and to explore the associated clinical and virological features in this patient population. The researchers conducted a retrospective cohort study on the 413 pediatric patients with chronic HBV infection from December 2011 to June 2022. The patients were stratified into two groups based on their anti-HBs status. Demographic, serum biochemical and virological parameters of two group were compared. Of the total 413 enrolled subjects, 94 (22.8%) were tested positive for both HBsAg and anti-HBs. Patients with anti-HBs were younger and demonstrated significantly higher ratio of albumin to globulin (A/G), elevated serum levels of alanine transaminase (ALT), lower ratio of aspartate transaminase (AST)/ALT (AST/ALT) and reduced serum levels of globulin, HBsAg and HBV DNA, Additionally, these patients were more likely to show coexistent HBeAg and anti-HBe when compared to patients without anti-HBs. The results of multivariate logistical analysis revealed that AST/ALT, serum levels of globulin and HBsAg were negatively associated with coexistence of HBsAg and anti-HBs. Our data demonstrated a considerable prevalence of coexisting HBsAg and anti-HBs in pediatric patients. Children with this specific serological pattern were commonly of a younger age, seemly predisposing them to early liver impairment and lower HBV replication activity.

Trajectories of serum HBsAg during treatment and association with HBsAg loss in children with HBeAg-positive chronic hepatitis B: a latent class trajectory analysis.

BACKGROUND: The change of serum hepatitis B surface antigen (HBsAg) during treatment are associated with HBsAg loss. However, little is known about the trajectory patterns of HBsAg in early treatment and their relationship with subsequent HBsAg loss. This study aimed to identify trajectories of HBsAg in children with HBeAg-positive chronic hepatitis B (CHB) and investigate the association between trajectory patterns and HBsAg loss. METHODS: A retrospective study was conducted on 166 treatment-naive children with HBeAg-positive CHB. Latent class trajectory analysis was used to identify trajectory groups of serum HBsAg. Cox proportional hazard model was used to assess the association between HBsAg trajectory groups and HBsAg loss. RESULTS: The median follow-up time was 20.70 (12.54, 34.17) months, and HBsAg loss occurred in 70(42.17%) of all study participants. Using latent class trajectory analysis, HBeAg-positive CHB patients were classified into three trajectory groups: trajectory 1 (sustained stability, 24.70%), trajectory 2 (slow decline, 38.55%), and trajectory 3 (rapid decline, 36.75%), respectively. The median decline levels of HBsAg at the 3-month and 6-month follow-ups were the highest in trajectory 3 (1.08 and 3.28 log10 IU/ml), followed by trajectory 2 (0.27 and 1.26 log10 IU/ml), and no change in trajectory 1. The risk of achieving HBsAg loss was higher in both trajectory 2 (HR, 3.65 [95% CI, 1.70-7.83]) and trajectory 3 (HR, 7.27 [95% CI, 3.01-17.61]), respectively. CONCLUSION: Serum HBsAg levels during early treatment can be classified into distinct trajectory groups, which may serve as an additional predictive indicator for HBsAg loss in HBeAg-positive CHB children.

Predictive role of early treatment dynamics of HBV RNA and HBcrAg for HBeAg seroconversion in children with chronic hepatitis B.

This study aimed to assess the predictive capacity of emerging serological markers, serum HBV RNA and HBcrAg, for HBeAg seroconversion in children with HBeAg-positive chronic hepatitis B (CHB). Treatment-naïve HBeAg-positive CHB children who admitted to the Liver Disease Center of Hunan Children's Hospital between April 2021 and September 2022 and received treatment with the combined entecavir and interferon-alpha treatment were recruited. Serum HBV RNA and HBcrAg were measured at baseline and Weeks 12, 24, and 48 of treatment. Our study showed that serum HBV RNA (HR = 0.71, 95% CI: 0.56-0.91, p = 0.006), HBcrAg (HR = 0.60, 95% CI: 0.43-0.84, p = 0.003), and HBsAg (HR = 0.49, 95%CI: 0.36-0.69, p < 0.001) at Week 12 were independent predictors of HBeAg seroconversion. ROC curve analysis presented that serum HBV RNA decline value (ΔHBV RNA) at Week 36 and HBcrAg decline value (ΔHBcrAg) at Week 12 (AUC = 0.871, p = 0.003 and AUC = 0.810, p = 0.003, respectively) could effectively predict HBeAg seroconversion. Furthermore, the optimal critical values were determined and the children with ΔHBV RNA > 3.759 log10 copies/mL at Week 36 or ΔHBcrAg >0.350 log10 U/mL at Week 12 more likely to achieve HBeAg seroconversion. The serum HBV RNA and HBcrAg provide new insights into the treatment of CHB in children. Early assessment of serum HBV RNA and HBcrAg during treatment can assist clinical decision-making and optimize individualized therapeutic approaches.

Characteristics and clinical treatment outcomes of chronic hepatitis B children with coexistence of hepatitis B surface antigen (HBsAg) and antibodies to HBsAg.

BACKGROUND: The coexistence of hepatitis B surface antigen (HBsAg) and hepatitis B surface antibody (HBsAb) represents an uncommon serological pattern observed in patients with hepatitis B virus (HBV) infection, and its underlying mechanism and clinical significance have not been well established. The aim of this study was to investigate the association between this serological profile and clinical treatment outcomes in children with chronic hepatitis B (CHB). METHODS: This retrospective cohort study included 372 treatment-naïve CHB children from the Hunan Children's Hospital. The participants were categorized into HBsAb-positive group and HBsAb-negative group. The associations between HBsAb positive status to clinical outcomes were assessed using Cox proportional hazard regression. Receiver operating characteristic curve was conducted to evaluate the prediction ability in HBsAg loss. RESULTS: The coexistence of HBsAg and HBsAb accounted for 23.39% (87/372) of the participants. The crude incidence rates of HBsAg loss, hepatitis B e antigen (HBeAg) clearance, and HBV-DNA undetectability were higher in the HBsAb-positive group compared with the HBsAb-negative group (37.46 vs. 17.37, 49.51 vs. 28.66, 92.11 vs. 66.54 per 100 person-years, respectively, all P < 0.05). The Cox regression analysis revealed a significant association between this serological profile and an increased likelihood of HBsAg loss (HR = 1.78, P = 0.001), and HBeAg clearance (HR = 1.78, P = 0.001). In addition, a combination of HBsAb ≥ 0.84 log10 IU/L and age ≤ 5 years can help identify patients likely to achieve HBsAg loss after antiviral therapy, with an AUC of 0.71. CONCLUSIONS: Children who are positive for both HBsAg and HBsAb demonstrate a higher probability of favorable outcomes after antiviral treatment. Thus, children with HBsAb-positive CHB should be actively treated to achieve functional cure.

Investigating the relationship between hepatitis B virus infection and postpartum depression in Chinese women: a retrospective cohort study.

Background: Postpartum depression (PPD) is associated with several psychological and obstetric factors. Hepatitis B virus (HBV) infection has been linked with a high risk of depression, but little is known about the relationship between maternal HBV infection and PPD. We aimed to investigate the association between HBV infection and PPD. Methods: This retrospective cohort study included 3,808 mothers who gave birth in a hospital in southern China. Self-reported Edinburgh Postnatal Depression Scale (EPDS) was used to assess PPD. Multivariate logistic regression was used to determine whether maternal HBV infection was associated with PPD risk. Results: Of the 3,808 participants, 11.9% of mothers had PPD at 6 weeks postpartum. Two hundred and seventy-eight (7.3%) and 3,530 (92.7%) were in the HBV and control groups, respectively. Women with HBV infection were more likely to test positive for PPD (14.7 vs.11.7%). The multivariate logistic regression analysis showed that HBV-infected women did not have a significantly higher incidence of PPD (OR = 1.23; 95% CI, 0.82-1.84) than those without HBV infection in the study cohort. Parity and postpartum hemorrhage were found to be associated with PPD. In addition, our study showed that e antigen positivity was not associated with PPD risk (OR = 0.56, 95% CI 0.19-1.63). Conclusions: To our knowledge, this is the first investigation of the relationship between maternal HBV infection and PPD. In a cohort of women without prior history or family history of mental illness, having HBV infection was not significantly associated with self-reporting of PPD compared to not having HBV infection.

Age at treatment initiation predicts response in children with chronic hepatitis B.

BACKGROUND: Accumulating evidence suggests that age has a significant impact on disease progression and outcome of hepatitis B virus (HBV) infection. However, its effect on treatment response has not yet been fully elucidated. AIM: To investigate the associations of age at treatment initiation with clinical treatment outcomes in children with chronic hepatitis B (CHB). METHODS: This study included 306 treatment-naïve children with CHB. Participants were divided into three groups based on the age at which they started antiviral treatment: 1-3 years, 4-6 years and 7-17 years. The primary outcome of this study was HBsAg loss; secondary outcomes included HBeAg clearance and DNA undetectability. RESULTS: Of the 306 subjects, 200 (65.4%) were male. Median (IQR) duration of follow-up was 26 (17, 42) months. There were 139 (45.4%), 79 (25.8%) and 88 (28.6%) of participants in the 1-3 years, 4-6 years and 7-17 years groups, respectively. After adjusting for other covariates, age at treatment initiation was negatively associated with the occurrence of HBsAg loss (1-3 years: HR = 5.07, 95% CI = 2.91-8.82; 4-6 years: HR = 2.42, 95% CI = 1.31-4.46) and HBeAg clearance (1-3 years: HR = 1.73, 95% CI = 1.18-2.53). In addition, we observed linear dose-responses relationships between age at treatment initiation and the probability of HBsAg loss and HBeAg clearance. CONCLUSIONS: In children with CHB receiving antiviral treatment, HBsAg loss and HBeAg clearance were frequently observed. Age at treatment initiation can predict treatment response, including HBsAg loss and HBeAg clearance.

Corrigendum: Investigating the relationship between hepatitis B virus infection and postpartum depression in Chinese women: a retrospective cohort study.

[This corrects the article DOI: 10.3389/fpubh.2023.1214151.].

Prevalence and Risk Factors for Fall among Rural Elderly: A County-Based Cross-Sectional Survey.

Aim: The aim of the study was to provide evidence for the prevention and reduction of falls in the elderly living in rural areas by analyzing epidemiological data of falls among the rural older people (>65 years old) and identifying the risk and protective factors. Methods: This study analyzed the sociodemographic characteristics, living environment, lifestyle, chronic disease condition, mental health, activities of daily living (ADL), and detailed information of falls of 3752 rural elderly. Rank tests, chi-square tests, and binary logistic regression were used for data analysis. Results: The prevalence of falls was 30.0%, and the 75-84-years age group had the highest fall rate (18.8%). According to the binary logistic regression analysis, six variables, including roughage intake frequency, age, gender, cane use, floor tiles, and IADL, were involved in the fall patterns. Low roughage intake (OR = 2.48, 95% CI 1.24-4.97), female gender (OR = 2.12, 95% CI 1.48-3.05), the use of a cane (OR = 2.11, 95% CI 1.08-4.10), and medium IADL (OR = 2.02, 95% CI 1.89-2.32) were the top four risk factors. Conclusion: The fall in the rural elderly was mainly due to the poor living and working conditions. Routine fall assessment could address several preventable risk factors to reduce the prevalence and mitigate the harm of falls.

Assessment of liver fibrosis by transient elastography and multi-parameters model in young children with chronic hepatitis B virus infection.

OBJECTIVE: This study aimed to compare the diagnostic value of the single or combined applications of transient elastography (TE) and multivariate indicators with biopsy for the detection of liver fibrosis in children caused by chronic hepatitis B (CHB). METHODS: This study included 148 CHB children treated at Hunan Children's Hospital from January 1st 2015 to December 31st 2018, aged from 0.83 to 14.58 years old. All patients underwent liver biopsy (LB), of which 43 patients underwent TE. Multiple clinical data, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), Platelet (PLT), and HBV-deoxyribonucleic acid (HBV DNA) of all patients were collected. The diagnostic values for CHB of TE and its combinations with these indicators were measured. The patients were classified in two ways: no hepatic fibrosis group (F0) versus fibrosis group (F ≥ 1), and no significant hepatic fibrosis group (F < 2) versus significant hepatic fibrosis group (F ≥ 2). The statistical assessment was performed between groups within each classification to compare the diagnostic value of different parameters. RESULTS: The operating characteristic area under curve (AUC) of liver fibrosis diagnosed by liver stiffness measurement (LSM) which obtained by TE, AST-to-PLT ratio index (APRI), and fibrosis-4 index (FIB-4) were 0.740, 0.701, and 0.651, while the corresponding cut-off values were 5.9 kPa, 0.50, and 0.10, respectively. The AUC of significant liver fibrosis diagnosed by LSM, APRI and FIB-4 were 0.849, 0.701, and 0.509, while the corresponding cut-off values were 8.4 kPa, 0.76, and 0.08, respectively. While with the combinations of LSM and APRI, LSM and FIB-4, LSM and APRI and FIB-4, APRI and FIB-4, the AUC of significant liver fibrosis were 0.866, 0.855, 0.869, and 0.684, respectively. The AUC of significant liver fibrosis diagnosed by the LSM was significantly higher than APRI and FIB-4. CONCLUSIONS: The diagnostic value of transient elastography was better than that of APRI and FIB-4 for CHB children with significant liver fibrosis. In addition, TE also has relatively high application values on the diagnosis of patients with different degrees of liver fibrosis caused by CHB.

Postpartum hemorrhage and postpartum depressive symptoms: A retrospective cohort study.

BACKGROUND: Many psychological and obstetrical factors contribute to the development of postpartum depression. However, little is known about how postpartum hemorrhage (PPH) influences postpartum depressive symptoms. This study explored the relationship between PPH and postpartum depressive symptoms in the Chinese population. METHODS: A retrospective cohort study was conducted at the Baoan Maternal and Child Health Hospital in Shenzhen, China, from January 2016 to June 2020. The Edinburgh Postnatal Depression Scale was used to assess postpartum depressive symptoms. A multivariate logistic regression model was used to estimate the odds ratios (ORs) with 95% confidence intervals (95% CIs) between PPH and risk of postpartum depressive symptoms. RESULTS: Of the 7734 respondents, 293 (3.8%) and 7441 were in the PPH and control groups, respectively. Puerperal women with PPH were more likely to screen positive for postpartum depressive symptoms than those without PPH (16.4% vs. 11.7%, p = .016). Adjusting for other covariates, women with PPH still had higher risk of postpartum depressive symptoms (OR = 1.68, 95% CI: 1.16-2.42). Stratification analyses revealed no interaction between PPH and maternal age, prepregnancy body mass index, mode of delivery, and fetal sex in developing depressive symptoms (p for interaction > .05). CONCLUSIONS: PPH may increase the risk of postpartum depressive symptoms. Therefore, women with PPH should be actively screened for depressive symptoms in the immediate postpartum period.

Prevalence and risk factors of postpartum depression in China: A hospital-based cross-sectional study.

BACKGROUND: Postpartum depression (PPD) is a major public health problem worldwide, which adversely affects maternal and infant health. The purpose of this study was to determine the prevalence and related factors of postpartum depression in Chinese puerperium women. METHODS: A cross-sectional study was conducted in Baoan Maternal and Child Health Hospital located in the west of Shenzhen, China. The Chinese version of the Edinburgh Postpartum Depression Scale (EPDS) was used to screen PPD. A score of ≥10 was used as the threshold of postpartum depression. RESULTS: A total of 4813 puerperal women were included in this study, 11.5% of whom were considered to have PPD. Multivariate logistic regression analysis found that family history of mental illness (OR = 1.94; 95% CI, 1.05-3.57; P = 0.033), living with parents-in-law (OR = 1.41; 95% CI, 1.16-1.72; P < 0.001), anxiety during pregnancy (OR = 3.66; 95% CI, 2.97-4. 52; P < 0.001), depression during pregnancy (OR = 4.25; 95% CI, 3.28-5.50; P < 0.001), and stressful life events (OR = 1.50; 95% CI, 1.03-2.20; P = 0.036) were associated with the high prevalence of PPD. LIMITATIONS: The cross-sectional survey cannot assess direct causality. EPDS is just a screening tool and not a diagnostic one. CONCLUSION: Postpartum depression is a common disease in Chinese puerperal population. High-risk pregnant women with postpartum depression need routine screening and targeted intervention for PPD.

Living With Parents-In-Law Increased the Risk of Postpartum Depression in Chinese Women.

Background: A variety of psychological and socioeconomic factors contribute to the development of postpartum depression (PPD). However, the relationship between maternal living arrangements and PPD is unclear. Objective: To assess the relationship between maternal living arrangements and PPD in Chinese population. Methods: A cross-sectional survey was conducted among puerperal women delivered in Baoan Maternal and Child Health Hospital in Shenzhen, China. The Edinburgh Postnatal Depression Scale (EPDS) was used to assess PPD. A score of ≥10 was used as the threshold for postpartum depression. Results: A total of 4,813 women were recruited, of whom 2,535 (52.7%) lived only with their husbands, 664 (13.8%) lived with their parents, and 1,614 (33.5%) lived with their parents-in-law. Compared with women who lived with husbands, puerperal women who lived with their parents-in-law were more likely to be positive for PPD screening (14.1 vs. 10.5%, P < 0.001). After adjusting for other influencing factors, living with parents-in-law was significantly associated with the risk of PPD (OR = 1.38, 95% CI, 1.12-1.70). Additionally, stratification analyses showed that the association between living with parents-in-law and the presence of PPD was more significant in women with anxiety during pregnancy (P for interaction <0.05). Conclusions and Relevance: Our data confirms that the maternal living arrangements affect the risk of PPD, especially among women with anxiety during pregnancy. Therefore, more targeted preventive measures should be taken for postpartum depression in women who live with their parents-in-law.

The prevalence of psychiatric symptoms of pregnant and non-pregnant women during the COVID-19 epidemic.

Coronavirus disease 2019 (COVID-19) is rapidly spreading worldwide, with a staggering number of cases and deaths. However, available data on the psychological impacts of COVID-19 on pregnant women are limited. The purposes of this study were to assess the prevalence of psychiatric symptoms among pregnant women, and to compare them with non-pregnant women. From February 28 to March 12, 2020, a cross-sectional study of pregnant and non-pregnant women was performed in China. The online questionnaire was used to collect information of participants. The mental health status was assessed by patient health questionnaire, generalized anxiety disorder scale, insomnia severity index, somatization subscale of the symptom checklist 90, and post-traumatic stress disorder (PTSD) checklist-5. Totally, 859 respondents were enrolled, including 544 pregnant women and 315 non-pregnant women. In this study, 5.3%, 6.8%, 2.4%, 2.6%, and 0.9% of pregnant women were identified to have symptoms of depression, anxiety, physical discomfort, insomnia, and PTSD, respectively. However, the corresponding prevalence rates among non-pregnant women were 17.5%, 17.5%, 2.5%, 5.4%, 5.7%, respectively. After adjusting for other covariates, we observed that pregnancy was associated a reduced risk of symptoms of depression (OR = 0.23; 95% CI: 0.12-0.45), anxiety (OR = 0.26; 95% CI: 0.16-0.42), insomnia (OR = 0.19; 95% CI: 0.06-0.58), and PTSD (OR = 0.15; 95% CI: 0.04-0.53) during the COVID-19 epidemic. Our results indicate that during the COVID-19 epidemic in China, pregnant women have an advantage of facing mental problems caused by COVID-19, showing fewer depression, anxiety, insomnia, and PTSD symptoms than non-pregnant women.

The potential role of clock genes in children attention-deficit/hyperactivity disorder.

BACKGROUND: Attention deficit/ hyperactivity disorder (ADHD) is a chronic neurodevelopmental disorder and is thought to be associated with circadian system. METHODS: We performed a pathway-based study to test individual single nucleotide polymorphisms (SNPs) and the overall evidence of genetic polymorphisms involved in the circadian pathway in association with children ADHD susceptibility among a Chinese population. A community-based case-control study was conducted among Chinese children, and 168 ADHD patients and 233 controls were recruited using a combination diagnosis based on the diagnostic and statistical manual of mental disorders iv (DSM-IV) ADHD rating scale, Swanson, Nolan, and Pelham rating scale (SNAP-IV) rating scale, and semi-structured clinical interview. RESULTS: The results of single-loci analyses identified that PER1 rs2518023 and ARNTL2 rs2306074 were nominally association with ADHD susceptibility (P < 0.05). Next, we applied multifactor dimensionality reduction (MDR), and classification and regression tree (CART) analyses to explore high-order gene-gene interactions among the functional SNPs to ADHD risks. The results indicated that interactions among the PER1 rs2518023, ARNTL2 rs2306074 and NR1D1 rs939347 were associated with the risk of ADHD in children. Individuals carrying the combination genotypes of the PER1 rs2518023 GG or GT, ARNTL2 rs2306074 TC or TT and NR1D1 rs939347 GA or AA displayed a significantly higher risk for ADHD than who carry the PER1 rs2518023 TT and CRY2 rs2292910 CA/CC genotypes (adjusted OR = 4.37, 95% CI = 2.16-8.85, P < 0.001). CONCLUSIONS: These findings revealed the importance of genetic variations related to the circadian clock system to the susceptibility of children ADHD.

Relationship between body composition indicators and risk of type 2 diabetes mellitus in Chinese adults.

BACKGROUND: Body composition is a crucial factor associated with the incidence of type 2 diabetes mellitus. However, no study on this relationship has been performed in the Chinese population. This study aimed to investigate the relationship between body composition indicators and risk of type 2 diabetes mellitus among Chinese adults undergoing medical examination. METHODS: Between January 2018 and July 2018, a retrospective cross-sectional study was performed on 3367 (2307 male and 1060 female) participants aged ≥18 years undergoing medical examination in Zhengzhou. Logistic regression analysis was performed to explore the relationship between body composition indicators and risk of type 2 diabetes mellitus. A receiver operating characteristic curve was used to calculate cutoff points and the predictive power of each indicator. RESULTS: Among the 3367 participants, 12.53% were diagnosed with type 2 diabetes mellitus. Multivariate logistic analysis indicated that male participants (odds ratio [OR] = 1.68, 95% confidence interval [CI]: 1.29-2.19), older participants (OR = 1.05, 95% CI: 1.04-1.06), participants with a waist-to-hip ratio above the reference value (OR = 1.56, 95% CI: 1.18-2.07), participants with body fat percentage above the reference value (OR = 1.62, 95% CI: 1.01-2.68), and participant with a large visceral fat area (OR = 1.01, 95% CI: 1.01-1.02) had a high risk of type 2 diabetes mellitus. Waist-to-hip ratio, body fat percentage, and visceral fat area were the best indicators of type 2 diabetes mellitus (P < 0.001) with cutoff values of 0.90, 25.02%, and 92.00 cm2, respectively. CONCLUSION: This study suggests a predictive relationship between type 2 diabetes mellitus and body composition indicators of waist-to-hip ratio, body fat percentage, and visceral fat area, which are valuable for screening diabetes and providing effective health education and behavioral intervention for high-risk populations.

Sex-specific influence of prenatal air pollutant exposure on neonatal neurobehavioral development and the sensitive window.

Increasing evidence indicates the adverse effect of air pollution exposure during pregnancy on neurologic development among children. However, the impact on neurobehavioral development in fetus remains unknown. In 2017, a total of 1193 mother-newborns pairs were enrolled in a birth cohort study in Changsha, China. Exposures to PM2.5, PM10, SO2, CO and NO2 were determined by using inverse distance weighted method based on local monitoring station data. Neurobehavioral measure was administered at 48-72 h postpartum by utilizing the neonatal behavioral neurological assessment (NBNA). Basic information and covariates were collected by face to face interview. Generalized linear regression and multivariable restricted cubic spline function were performed to explore the trimester-specific association and dose-response relationship of maternal air pollution exposure with NBNA score, respectively. In adjusted three-pollutant model, PM2.5 exposure in trimester 2 was negatively associated with behavior score (ß, -0.003; 95% CI, -0.006, -0.001) and the inverse relation was more pronounced in male infants. In addition, PM2.5 level in the 2nd trimester was negatively related to activetone score (ß, -0.012; 95% CI, -0.021, -0.002) in a dose-dependent manner for both genders. Collectively, our results demonstrated that prenatal exposure to PM2.5 was linked to poor neurobehavioral performance of newborns. The second trimester was the most sensitive time window for the developments of behavior and activetone, and male subject was more vulnerable as compared to females.