Children's Neurobehavioral Development Research Articles

Association between cord blood BPDE-DNA and neurodevelopment of children aged 0 and 2 years: A birth cohort study

Objective: To explore the effects of mothers' exposure to polycyclic aromatic hydrocarbons during pregnancy on their children's neurobehavioral development. Methods: In November 2009 to April 2010, a total of 221 pairs of mother-newborn pairs were recruited from two cooperative hospitals in Taiyuan, and their children were followed up at age two. High performance liquid chromatography was used to determine the level of BPDE-DNA in cord blood leukocytes. The Neonatal behavioral neurological assessment (NBNA) was used to assess the neurodevelopment of newborns, and the Gesell Development Scale was used to measure neurodevelopmental indexes of 2-year-old children. NBNA includes behavior, active and passive tone, primitive reflexes and general assessment, with a total score of 40 points. The Gesell Developmental Schedules consisted of four sub-scales: motor development, adaptive behavior development, language development and personal-social behavior development. We used mean and standard deviation to describe continuous variables with normal distribution, median (interquartile range) to describe continuous variables with skewed distribution, and frequency and proportion to describe categorical variables. Restricted cubic spline models were applied to assess the dose-response relationships between maternal prenatal polycyclic aromatic hydrocarbons exposure and children's neurobehavioral development at two years old. Generalized linear models were applied to evaluate the effect of exposure to maternal prenatal polycyclic aromatic hydrocarbons exposure on children's neurobehavioral development at 0 and two years old. Results: The NBNA score was 38.0±0.8, and the scores of 2-year-old children's motor, adaptive, language and personal-social were 111.6±15.0, 110.5±14.6, 108.8±17.2 and 111.7±14.5, respectively. After adjusting for confounding factors, there is no dose-response association between the cord blood BPDE of pregnant women and neonatal NBNA scores, but there were dose-response associations between BPDE and scores of 2-year-old children's motor, adaptive, language and personal-social. A unit increase in cord blood ln (BPDE-DNA), the score of motor, adaptive, language and personal-social of 2-year-old children decreased on average by 4.54、6.29、8.41 and 7.02 points. Conclusion: Maternal exposure to polycyclic aromatic hydrocarbons during pregnancy is associated with decreased children's neurobehavioral development at two years old.

Prenatal bisphenol A exposure, fetal thyroid hormones and neurobehavioral development in children at 2 and 4 years: A prospective cohort study

Findings about the association between prenatal Bisphenol A (BPA) exposure and neurobehavioral development in children are still inconsistent. In addition, whether fetal thyroid hormones (THs) mediate the reported association remains unclear. The present study aimed to examine the association between prenatal BPA exposure and risks of child behavioral problems at 2 and 4 years of age and whether the association could be explained by alteration of fetal THs as measured in cord plasma. Using the Shanghai-Minhang Birth Cohort Study (S-MBCS), BPA concentration was measured in maternal urine samples collected at 12–16 weeks of gestation. Children's neurobehavioral development was assessed using the Child Behavior Checklist/1.5–5 (CBCL), at 2 and 4 years of age. Using generalized estimating equation (GEE) models, 745 mother-pairs were included to examine associations of BPA with CBCL scores, Using multiple linear regression models, 348 mother-pairs were included to evaluate the association between maternal BPA and THs in cord plasma. A mediation analysis was conducted to explore the potential mediating role of THs. After adjusting for potential confounders, prenatal BPA level was associated with increased risks of Emotionally Reactive problem, Anxious/Depressed problem, having Somatic Complaints, exhibiting Aggressive Behavior, and Internalizing and Externalizing Problems: compared to the lowest tertile, the risks in the highest tertile and middle tertile, ranged between 1.55-fold (95% CI: 1.09, 2.21) and 2.59-fold (95% CI: 1.52, 4.42). The association was more pronounced among boys. None of the associations reached statistical significance among girls. An inverse association between prenatal BPA and fetal TH level was also observed. However, the observed neurotoxic effects of prenatal BPA exposure did not appear to be mediated by THs levels. The current findings suggest that prenatal exposure to BPA may disrupt fetal THs levels and may induce long-lasting behavioral alterations, especially in boys.

Associations of prenatal exposures to low levels of Polybrominated Diphenyl Ether (PBDE) with thyroid hormones in cord plasma and neurobehavioral development in children at 2 and 4 years

BackgroundNeurotoxic effects of Polybrominated Diphenyl Ethers (PBDEs) at low levels have not been well studied in human population, and whether the associations can be explained by thyroid hormones (THs) remains unclear. ObjectivesWe examined the associations of prenatal PBDE exposures with THs in cord plasma and neurobehavior of children at 2 and 4 years among general population in China. MethodsParticipants were mother-child pairs in the Shanghai-Minhang Birth Cohort Study. Nine PBDE congeners and THs (thyroid stimulating hormone, total thyroxine, free thyroxine, total triiodothyronine, and free triiodothyronine) were determined in cord plasma. Child Behavior Checklist (CBCL/1.5-5) were completed by caregivers to assess children's neurobehavioral development at 2 and 4 years. In the final analyses, 199 and 307 mother-child pairs at 2 and 4 years were included to examine associations of PBDEs with CBCL scores using Pearson-scale-adjusted Poisson regressions, and 339 subjects were included in linear regression models to investigate the associations between PBDEs and THs. ResultsBDE-47 had the highest detection rate of 83.82% with the median concentration of 0.19 ng/g lipid, followed by BDE-28, −99, −100 and −153 with detection rates nearly 50%. We found positive associations between prenatal PBDE concentrations and children's neurobehavior, including Somatic Complaints, Withdrawn, Sleep Problems and Internalizing Problems in girls, and Somatic Complaints and Attention Problems in boys. We also observed inverse associations of the sum of BDE-47, −28, −99, −100 and −153 with THs. However, by adding THs to the models examining associations between PBDEs and CBCL, the main results didn't measurably change. ConclusionsThis study adds new knowledge that prenatal PBDEs at low levels may be related to long-lasting behavioral abnormalities in children and reduced THs in cord plasma. However, the hypothesis that the neurotoxic impact of PBDEs may be explained by alterations in cord THs was not supported.

Relation of prenatal low-level mercury exposure with early child neurobehavioral development and exploration of the effects of sex and DHA on it

BackgroundThe extent to which low-level, in utero mercury exposure affects child neurobehavioral development during early childhood has been inconclusive. In addition, the effects of sex and docosahexaenoic acid (DHA) on these relationships remain unclear and controversial. ObjectivesThis study aimed to explore the associations between prenatal low-level mercury exposure and child neurobehavioral development during the neonatal and toddler periods and to examine the potential confounding or interactive effects of sex and DHA status on these relationships. MethodsThis longitudinal study included 286 mother-child pairs in Shanghai, China, whose cord blood samples were analyzed for total mercury, DHA, other nutrients and coexposure contaminants possibly due to maternal consumption of seafood. Children's neurobehavioral development was assessed with the Neonatal Behavioral Neurological Assessment (NBNA) three days after birth and the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) at 18 months of age. ResultsCord blood mercury concentration, with geometric mean of 2.00 μg/l, was related to poorer NBNA performance but unrelated to BSID-III scores with adjustment for DHA and other covariates. Cord serum DHA was positively associated with motor development assessed by the BSID-III. The interaction was found between mercury and DHA on the NBNA score, and the inverse relation of cord blood mercury with NBNA was significant only among the children with lower DHA levels (<45.54 μg/ml). Additional adjustment for DHA didn't change the associations between cord blood mercury and neurodevelopmental outcomes substantially. The mercury by sex interaction for language of BSID-III was borderline significant. ConclusionsOur research provides initial evidence for the negative effects of prenatal low-level mercury exposure on neonates' neurobehavioral development. Prenatal DHA status may modify the relationship between cord blood mercury level and neonatal neurobehavioral development, but the confounding effects of DHA were not observed. Further studies are warranted before the causality of the observed associations can be determined.

Prevalencia del riesgo de alteraciones en el desarrollo neuroconductual en una población de lactantes de México en 2012

El objetivo de este estudio fue determinar la prevalencia del riesgo para alteraciones del desarrollo de lactantes de una región del sureste de México, utilizando el instrumento de valoración neuroconductual del desarrollo del lactante VANEDELA. Los niños identificados fueron aptos para recibir estimulación temprana o rehabilitación. Se estudiaron 118 lactantes con edades de 1 a 24 meses, con un promedio de 6,4 meses, con riesgo leve para alteración en un 34 %, riesgo alto en un 7 % de los lactantes y el 59 % desarrollo normal. En la valoración de conductas del desarrollo, la mayor prevalencia de afectación se presentó en áreas de los sistemas motor fino (27,3 %) y cognoscitivo, lenguaje en un 25 % en todas las etapas. El 12 % de lactantes de 4 meses presentó reacciones del desarrollo ausentes y un 6 % de la muestra tuvo signos de alarma, razón por la que fueron remitidos para valoración en el laboratorio de rehabilitación. La prueba VANEDELA fue suficientemente precisa para determinar el riesgo de alteraciones del desarrollo neuroconductual, siendo un test tamizaje utilizado en población aparentemente sana y para sugerir programas integrales de atención temprana o fortalecer los existentes.

Gender difference in the effects of lead exposure at different time windows on neurobehavioral development in 5-year-old children

BackgroundAlthough the association between lead exposure and children's neurodevelopment has been studied, gender differences remain to be investigated. We examined the effects of lead exposure on the neurobehavioral development of 5-year-old children to identify the vulnerable time window of exposure and potential gender difference. MethodA total of 1751 pregnant women and children participated in the prospective birth cohort study, Mothers and Children's Environmental Health study, since 2006. Lead levels were measured in the maternal blood in early and late pregnancies, in cord blood at birth, and in 2-, 3-, and 5-year-old children's blood. The behavior of 575 children aged 5years were assessed using the Korean Child Behavior Checklist. The association between the blood lead level at each time window and behavior was examined using a generalized linear model adjusted for potential confounders and covariates. ResultsLead levels at late pregnancy were significantly associated with increased risk of behavioral problems in males. Lead levels in 2- and 5-year-old children's blood significantly increased behavioral risks in females: for a 1-μg/dL increase in blood lead levels, the score for total behavioral problems increased by 3.00 (95% confidence interval [CI]: 0.56–5.45) during the late pregnancy in males, whereas it increased by 3.82 (95% CI: 1.25–6.39) at 2years and by 5.72 (95% CI: 0.44–10.99) at 5years in females with a stronger effect in attention and sleep problems. ConclusionEffects of lead toxicity on children's neurobehavioral development showed gender differences. Males were more susceptible to prenatal exposure, while females were more susceptible to postnatal exposure with stronger effects in attention and sleep problems.

Prenatal phenolic compounds exposure and neurobehavioral development at 2 and 7 years of age

BackgroundPhenolic compounds such as bisphenol A (BPA), nonylphenol (NP), and octylphenol (OP) are known as endocrine-disrupting compounds and are commonly used. Their impacts on the neurodevelopment of children are inconclusive. The current study aims to investigate the association between umbilical cord blood levels of BPA, NP, OP and neurodevelopmental outcomes at 2 and 7years of age. MethodsThe study was based on the Taiwan Birth Panel Study, a prospective birth cohort. We collected cord blood plasma to measure phenolic compound levels using ultra-performance liquid chromatography-tandem mass spectrometry. In the follow-up, 208 mother-child pairs with 2-year-old children and 148 mother-child pairs with 7-year-old children were recruited in this study. We used the Comprehensive Developmental Inventory for Infants and Toddlers (CDIIT) and the Wechsler Intelligence Scale for Children (WISC-IV) for neurodevelopmental assessments at 2 and 7years of age, respectively. Multiple linear regressions were used for statistical analysis. ResultsThe detection rates of BPA, NP, and OP were 55.9%, 77.6%, and 68.3%, respectively. In this study, the median BPA, NP, and OP levels in 2-year-olds were 3.3, 72.6, and 3.3 (ng/ml), respectively. However, the median levels of BPA, NP, and OP were 3.2, 49.3, and 6.6 (ng/ml), respectively. The levels of phenolic compounds were log10-transformed for statistical analysis. Gender stratification was performed. In the WISC-IV neurocognitive assessment, we found both a significant negative association and a trend between cord blood plasma BPA levels and full-scale IQ (p for trend<0.01), the verbal comprehension index (p for trend<0.01), and the perceptual reasoning index (p for trend<0.01) in the study population. After stratification by sex, significant associations were found in full-scale IQ (p for trend=0.03) and the verbal comprehension (p for trend<0.01) index in boys. In girls, prenatal BPA exposure had adverse effects on full-scale IQ (p for trend=0.02), perceptual reasoning index (p for trend<0.01), and working memory index (p for trend=0.02). None of the developmental quotients (DQs) of the CDIIT analysis were significantly associated with phenolic compound levels in cord blood based on continuous or categorical measures. ConclusionPrenatal exposure to BPA affects neurocognitive development, and this effect differs between 7-year-old boys and girls. More studies are needed to elucidate the relationship between phenolic compound exposure in utero and children's neurobehavioral development.

Employment in the Ecuadorian cut-flower industry and the risk of spontaneous abortion

BackgroundResearch on the potentially adverse effects of occupational pesticide exposure on risk of spontaneous abortion (SAB) is limited, particularly among female agricultural workers residing in developing countries.MethodsReproductive histories were obtained from 217 Ecuadorian mothers participating in a study focusing on occupational pesticide exposure and children's neurobehavioral development. Only women with 2+ pregnancies were included in this study (n = 153). Gravidity, parity and frequency of SAB were compared between women with and without a history of working in the cut-flower industry in the previous 6 years. Logistic regression analysis was conducted to assess the relation between SAB and employment in the flower industry adjusting for maternal age.ResultsIn comparison to women not working in the flower industry, women working in the flower industry were significantly younger (27 versus 32 years) and of lower gravidity (3.3 versus 4.5) and reported more pregnancy losses. A 2.6 (95% CI: 1.03-6.7) fold increase in the odds of pregnancy loss among exposed women was observed after adjusting for age. Odds of reporting an SAB increased with duration of flower employment, increasing to 3.4 (95% CI: 1.3, 8.8) among women working 4 to 6 years in the flower industry compared to women who did not work in the flower industry.ConclusionThis exploratory analysis suggests a potential adverse association between employment in the cut-flower industry and SAB. Study limitations include the absence of a temporal relation between exposure and SAB, no quantification of specific pesticides, and residual confounding such as physical stressors (i.e., standing). Considering that approximately half of the Ecuadorian flower laborers are women, our results emphasize the need for an evaluating the reproductive health effects of employment in the flower industry on reproductive health in this population.

CYP1A1 Ile462Val and GSTT1 modify the effect of cord blood cotinine on neurodevelopment at 2 years of age

Maternal exposure to environmental tobacco smoke (ETS) has been reported to be associated with children's neurobehavioral development but there was no studies investigating the genetic susceptibilities to maternal ETS exposure on children's neurodevelopment. The aim of the study was to explore the modification effect of metabolic gene polymorphisms to cord blood cotinine on children's neurodevelopment at the 2 years of age. This study is one investigation of the Taiwan Birth Panel Study and a total of 145 pregnant women and their neonates were recruited between April 2004 and January 2005. We interviewed them by a structured questionnaire after delivery and collected umbilical cord blood at birth. Cotinine in umbilical cord blood as an indicator of environmental tobacco smoke was analyzed by using HPLC–MS/MS and the detection limited of this method was 0.05 ng/mL. Four metabolic genes, CYP1A1 MspI, CYP1A1 Ile462Val, GSTT1 and GSTM1 were identified. The Comprehensive Developmental Inventory for Infants and Toddlers (CDIIT) was used for assessing children's neurodevelopment at the 2 years of age accompanying with the measurement of Home Observation for Measurement of the Environment scale. We used multiple linear regression models to estimate the effects of cord blood cotinine and gene modification. Cotinine levels were significantly negatively associated with developmental quotients (DQs) of the whole test, and cognitive, language, fine-motor and social subtests of the CDIIT. Lower cognitive and language DQs were found in exposed group with absent type of GSTT1. In addition, the lowest scores in fine-motor and whole test DQs were detected in exposed group with CYP1A1 Ile462Val variant type and GSTT1 absent type. It can be concluded that CYP1A1 Ile462Val and GSTT1 metabolic genes can modify the effect of cord blood cotinine on early child neurodevelopment especially for language and fine motor development.

Exposure to Endocrine Disrupting Chemicals and Children's Health: Problems in Epidemiological Studies

Most endocrine disrupting chemicals are characterized by their properties to induce marked phenotypic changes in offspring such as congenital anomalies and neurodevelopmental dysfunctions. Although an increase in the prevalence of hypospadias or cryptorchidism has been reported in various countries, improvement in diagnostic techniques and more attention to the features of the diseases have also been emphasized. Although there have been a few reports that hypospadias or cryptorchidism had been associated with diethylstilbestrol (DES), pesticides and so on, the associations between these diseases and endocrine disrupting chemicals remain unclear. Recently, the association between maternal metabolic polymorphism or paternal smoking during pregnancy and these diseases has been reported. There are also variable clinical features in children's neurobehavioral development, and thyroid and immune functions in relation to exposure to endocrine disrupting chemicals such as polychlorinated biphenyls (PCBs) and dioxins. Only a few Dutch studies have suggested that perinatal exposure to background level of PCB/dioxin confers immunity to allergy development. Genetic susceptibility to environmental endocrine disrupting chemicals may be related to adverse pregnancy outcomes. It is suggested that well-designed epidemiological studies such as prospective cohort studies should be performed to elucidate this association.

Pesticides and Polychlorinated Biphenyls (PCBs): An Analysis of the Evidence That They Impair Children's Neurobehavioral Development

Pesticides and Polychlorinated Biphenyls (PCBs): An Analysis of the Evidence That They Impair Children's Neurobehavioral Development