Prenatal and early postnatal phthalate exposure and child neurodevelopment at age of 7 years - Polish Mother and Child Cohort.

Phthalates are among the most frequently investigated environmental chemicals influencing children's health and particularly their neuropsychological development. However, the reported effects of these compounds on child behavior, cognitive and psychomotor outcomes are not fully consistent. The aim of this study is to evaluate the associations between prenatal and early postnatal phthalate exposures and child neurodevelopment at age of 7 years. A total of 134 mother-child pairs from Polish Mother and Child Cohort (REPRO_PL) constitute the basis for current analysis. Eleven phthalate metabolites were measured in urine samples collected from mothers in the 3rd trimester of pregnancy and from children at the age of 2 years. Child neuropsychological development at early school age (7 years) was assessed by both the Strengths and Difficulties Questionnaire (SDQ) filled by mothers and the Polish adaptation of the Intelligence and Development Scales (IDS) performed by psychologists. Mono-ethyl phthalate (MEP) concentration during pregnancy was significantly associated with increased risk of peer relationship problems in SDQ (OR = 2.7, p = 0.03). The results of the IDS analyses focused on child's cognitive and psychomotor development are not fully conclusive. Negative associations were evident between some phthalates in early childhood period and fluid intelligence and cognition (MEP: ß = -5.2; p = 0.006; ß = -4.2; p = 0.006; mono-n-butyl phthalate (MnBP): ß = -4.9; p = 0.03; ß = -4.0; p = 0.03; respectively), while positive associations have been found in the prenatal period (mono-2-ethyl-5-oxo-hexyl phthalate (oxo-MEHP): ß = 3.6; p = 0.03 for fluid intelligence; ß = 2.9; p = 0.03 for cognition). Further studies are required in order to elucidate which are the most critical periods of phthalate exposure on children's neurodevelopmental outcomes.

Phthalate exposure and neurodevelopmental outcomes in early school age children from Poland.

Some phthalates are known endocrine disrupting chemicals (EDC). They are widely present in the environment thus their impact on children's health is of particular scientific interest. The aim of the study was to evaluate the association between phthalate exposure and neurodevelopmental outcomes, in particular behavioral, cognitive and psychomotor development, in 250 early school age children from the Polish Mother and Child Cohort (REPRO_PL). Urine samples were collected at the time of children's neurodevelopmental assessment and were analysed for 21 metabolites of 11 parent phthalates. Behavioral and emotional problems were assessed by the Strengths and Difficulties Questionnaire (SDQ) filled in by the mothers. To assess children's cognitive and psychomotor development, Polish adaptation of the Intelligence and Development Scales (IDS) was administered. The examination was performed by trained psychologists. Dimethyl phthalate (DMP) and di-n-butyl phthalate (DnBP) were the two phthalates showing the highest statistically significant associations, with higher total difficulties scores (ß = 1.5, 95% CI 0.17; 2.7; ß = 1.5, 95% CI 0.25; 2.8, respectively) as well as emotional symptoms and hyperactivity/inattention problems for DnBP (ß = 0.46, 95% CI -0.024; 0.94; ß = 0.72, 95% CI 0.065; 1.4, respectively), and peer relationships problems for DMP (ß = 0.37, 95% CI -0.013; 0.76). In addition, DnBP and DMP have been found to be negatively associated with fluid IQ (ß = -0.14, 95% CI -0.29; 0.0041) and crystallized IQ (ß = -0.16, 95% CI -0.29; -0.025), respectively. In the case of mathematical skills, three phthalates, namely DMP (ß = -0.17, 95% CI -0.31; -0.033), DEP (ß = -0.16, 95% CI -0.29; -0.018) and DnBP (ß = -0.14, 95% CI -0.28; 0.0012), have also shown statistically significant associations. This study indicates that exposure to some phthalates seems to be associated with adverse effects on behavioral and cognitive development of early school age children. Further action including legislation, educational and interventional activities to protect this vulnerable population is still needed.

Determinants of the Essential Elements and Vitamins Intake and Status during Pregnancy: A Descriptive Study in Polish Mother and Child Cohort.

The study objective was to identify determinants of essential elements and vitamins intake, and microelements and vitamins concentration in blood among pregnant women from Poland. Based on the data from food frequency questionnaires and information about supplements taken (n = 1252), daily supply of six elements (calcium, magnesium, iron, zinc, copper, selenium) and nine vitamins (folate, vitamins A, E, C, B1, B2, B3, B6, B12) was calculated. Zinc, copper, selenium (n = 340), vitamin A and E (n = 358) concentration was determined in blood collected during pregnancy. Most of the women did not meet the demand for essential elements and vitamins with a diet. About 94% of the respondents declared supplements use. The women with higher education, indicating leisure-time, physical activity and multiparity had a higher chance of meeting the average demand for the majority of the analyzed nutrients. On the other hand, factors such as BMI < 18.5kg/m2, a higher level of stress, and late first medical-care visit were associated with a lower chance of meeting the recommendations. Higher socio-economic status was a determinant of a higher selenium concentration in plasma (ß = 3.1; 95%CI: 0.2-5.9), whereas BMI ≥ 25 kg/m2, and multiparity of a higher copper concentration in plasma (ß = 0.2; 95%CI: 0.03-0.4; ß = 0.2; 95%CI: 0.1-0.4). Higher plasma concentration of vitamin E was noted among women older than 30 years of age comparing to those who were 30 or younger (ß = 1.5; 95%CI: 0.6-2.4). Although more studies are required, especially such based on laboratory measures, our results indicate target groups for dietary interventions during pregnancy for children's optimal health and development.

Dietary Quality and Dietary Inflammatory Potential During Pregnancy and Offspring Emotional and Behavioral Symptoms in Childhood: An Individual Participant Data Meta-analysis of Four European Cohorts.

BACKGROUND: The impact of maternal diet during pregnancy on child neurodevelopment is of public health and clinical relevance. We evaluated the associations of dietary quality based on the Dietary Approaches to Stop Hypertension (DASH) score and dietary inflammatory potential based on the energy-adjusted Dietary Inflammatory Index (E-DII) score during pregnancy with emotional and behavioral symptoms of offspring at 7 to 10 years of age. METHODS: Individual participant data for 11,870 mother-child pairs from four European cohorts participating in the ALPHABET project were analyzed. Maternal antenatal DASH and E-DII scores were generated from self-completed food frequency questionnaires. Symptoms of depression and anxiety, aggressive behavior, and attention-deficit/hyperactivity disorder in children were assessed using mother-reported tests and classified within the normal or borderline/clinical ranges using validated cutoffs. Adjusted odds ratios were determined by multivariable logistic regression models and aggregated by the two-level individual participant data meta-analysis method. RESULTS: Higher maternal DASH scores (indicating better dietary quality) were associated with lower risk of depressive and anxiety symptoms, aggressive behavior symptoms, and attention-deficit/hyperactivity disorder symptoms within the borderline/clinical ranges: odds ratio [OR] 0.97, 95% confidence interval [CI], 0.95-0.99; OR 0.97, 95% CI, 0.94-0.99; OR 0.97, 95% CI, 0.95-0.98, per one-unit DASH score increase, respectively. For depression and anxiety, aggressive behavior, and attention-deficit/hyperactivity disorder symptoms, a one-unit increase in E-DII scores (a more proinflammatory diet) was associated with a 7% increased risk of all three analyzed emotional and behavioral symptoms: OR 1.07, 95% CI, 1.03-1.11; OR 1.07, 95% CI, 1.02-1.13; OR 1.07, 95% CI, 1.01-1.13, respectively. CONCLUSIONS: Our findings suggest that a maternal low-quality and proinflammatory diet may increase the risk of emotional and behavioral symptoms in children.

Sociodemographic, Lifestyle, Environmental and Pregnancy-Related Determinants of Dietary Patterns during Pregnancy.

Background: Characterization of dietary patterns represents a valid and meaningful measure of overall diet quality and nutrient intake. The study aims at evaluating the sociodemographic, lifestyle, environmental, and pregnancy-related determinants of maternal dietary patterns during pregnancy. Methods: The analysis was conducted on a group of pregnant women from the Polish Mother and Child Cohort (REPRO_PL). During the second trimester of pregnancy, 1306 women filled in a modified version of the validated food frequency questionnaire (FFQ). Dietary patterns were estimated using an exploratory factor analysis. Potential dietary determinants were assessed via a questionnaire or biomarker measurements (saliva cotinine level). Results: Two dietary patterns were identified. The Prudent dietary pattern was characterized by high consumption of fruit, vegetables, legumes, whole grains, poultry, and low-fat dairy products, while the Western dietary pattern included high intake of refined grains, processed meat, potatoes, and very low intake of whole grains. Clear sociodemographic, environmental, lifestyle, and pregnancy-related determinants of diet quality were established. Older age (ß = 0.2; p < 0.01), higher educational level (ß = 0.3; p < 0.01), and socioeconomic status (SES) (ß = 0.2; p < 0.01), overweight/obesity before (ß = 0.3; p < 0.01), as well as physical activity during pregnancy (ß = 0.2; p = 0.01) were positive determinants of a healthier diet (increasing Prudent⁻Western difference in dietary pattern scores). On the other hand, parity (ß = -0.2; p = 0.04) and living in small cities (ß = -0.3; p = 0.02) were significantly related to a rather Western dietary pattern. Conclusions: The current study presents evidence on specific factors influencing dietary patterns. They need to be accounted for in educational programs and interventions focused on healthy diet recommendations during pregnancy.

Determinants of phthalate exposure and risk assessment in children from Poland.

Phthalates are a group of widely used chemicals and humans are exposed to them in their daily life. Some phthalates may affect the hormonal balance in both children and adults. The aim of this study was to assess the phthalate exposure and its determinants among children at age of 7 years from the Polish Mother and Child Cohort Study (REPRO_PL). 250 urine samples collected in 2014-2015 were analysed for 21 metabolites of 11 parent phthalates using on-line high performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS). This represents the most extensive set of phthalate metabolites ever determined for Poland. Ten metabolites were quantifiable in 100% of the samples, another eight in >90%. The highest median concentrations were found for the primary monoester metabolites of di-iso-butyl (MiBP, 72.4 µg/l), di-n-butyl (MnBP, 56.3 µg/l) and diethyl (MEP, 42.0 µg/l) phthalate, followed by the sum of di-2-ethylhexyl (ΣDEHP, 89.3 µg/l) and di-iso-nonyl (ΣDiNP, 21.9 µg/l) phthalate metabolites. Metabolite concentrations were higher in children at 7 years than in the same children at age 2 or in their mothers during pregnancy. Generally, phthalate exposures in this study were much higher than exposures reported in other European populations. Multivariate regression models showed that body mass index, place of residence, breastfeeding duration, socio-economic status and parental education were associated with the metabolite levels in the 7-year old children. Daily intake and hazard index calculations revealed that a small percentage of children (around 3-10%) exceeded the tolerable daily intakes established by international institutions such as EFSA and U.S. EPA indicating that these children might be at risk of anti-androgenic effects from the individual and cumulative exposure to phthalates. Thus, further monitoring of this population, by educational programs and follow-up interventions, is required.

Sex-Dependent Impact of Low-Level Lead Exposure during Prenatal Period on Child Psychomotor Functions.

The impact of exposure to lead on child neurodevelopment has been well established. However, sex differences in vulnerability are still not fully explained. We aimed at evaluating the effect of a low-level lead exposure, as measured between 20 to 24 weeks of pregnancy and in cord blood, on developmental scores up to 24 months of age in 402 children from the Polish Mother and Child Cohort (REPRO_PL). Additionally, sex-dependent susceptibility to lead at this very early stage of psychomotor development was assessed. The blood lead levels were analyzed using inductively coupled plasma mass spectrometry (ICP-MS). In order to estimate the children's neurodevelopment, the Bayley Scales of Infant and Toddler Development was applied. The geometric mean (GM) for blood lead level during 20⁻24 weeks of pregnancy was 0.99 ± 0.15 µg/dL and, in the cord blood, it was 0.96 ± 0.16 µg/dL. There was no statistically significant impact of lead exposure during prenatal period on the girls' psychomotor abilities. Among the boys, we observed lower scores for cognitive functions, along with increasing cord blood lead levels (ß = -2.07; p = 0.04), whereas the results for the language and motor abilities were not statistically significant (p > 0.05). Our findings show that fetal exposure to very low lead levels might affect early cognitive domain, with boys being more susceptible than girls. Education on health, higher public awareness, as well as intervention programs, along with relevant regulations, are still needed to reduce risks for the vulnerable population subgroups.

Current overview of extrinsic and intrinsic factors in etiology and progression of inflammatory bowel diseases.

Inflammatory bowel diseases (IBD) are chronic, relapsing disorders affecting gastrointestinal (GI) tract and associated with intestinal mucosa damage and inflammation. The principal therapeutic goals in IBD include control of the intestinal inflammation and treatment of the major symptoms, mainly abdominal pain and diarrhea. Current therapeutic strategies for IBD rely on the use of non-specific anti-inflammatory agents and immunosuppressive drugs (e.g. aminosalicylates, monoclonal antibodies, and antibiotics), which cause severe side effects, and - in a significant number of patients - do not induce long-term benefits. In this review, we summarize the epidemiology and the most important risk factors of IBD, including genetic, immunological and environmental. Our main focus is to discuss pharmacological targets for current and future treatments of IBD.