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Early life is a crucial window of opportunity to improve health across the life course. The prospective cohort study design is the most adequate to evaluate the longitudinal effects of exposure, the notification of changes in the exposure level and evaluation of the simultaneous impact of various exposures, as well as the assessment of several health effects and trajectories throughout childhood and adolescence. This paper provides an overview of the Polish Mother and Child cohort (REPRO_PL), with particular emphasis on Phase IV of this study. REPRO_PL is conducted in central Europe, where such longitudinal studies are less frequently implemented. In this population-based prospective cohort, which was established in 2007, three phases covering pregnancy (I), early childhood (II), and early school age (III) periods have already been completed. Phase IV gives a uniform opportunity to follow-up children during adolescence in order to evaluate if the consequences of prenatal and early postnatal exposures still persist at the age of 14. Moreover, we will be able to investigate the associations between simultaneous exposures to a broad spectrum of environmental factors, adolescents' health and neurobehavioral outcomes, and their trajectories within life, which is a novel framework of high scientific, public health and clinical priority., This study was supported by the grants from the National Science Centre (Nos. 2014/15/B/NZ7/00998, 2017/25/B/NZ5/02338, and 2021/41/B/NZ7/04341). MG acknowledges the support from the IDAEA-CSIC Severo Ochoa Excellence Programme through the Grant CEX 2018-000894-S funded by MCIN/AEI/10.039/501100011033.

Objective: Birth cohorts collect valuable and under-utilized information on employment and health of parents before and during pregnancy, at birth, and sometimes after birth. In this discussion paper, we examine how these data could be exploited to study the complex relationships and interactions between parenthood, work, and health among parents themselves. Methods: Using a web-based database of birth cohorts, we summarize information on maternal employment and health conditions and other potentially related variables in cohorts spread throughout Europe. This provided information on what data are available and could be used in future studies, and what was missing if specific questions are to be addressed, exploiting the opportunity to explore work-health associations across heterogenous geographical and social contexts. Results: We highlight the many potentialities provided by birth cohorts and identify gaps that need to be addressed to adopt a life-course approach and investigate topics specific to the peri-pregnancy period, such as psychosocial aspects. We address the technical difficulties implied by data harmonization and the ethical challenges related to the repurposing of data, and provide scientific, ecological and economic arguments in favor of improving the value of data already available as a result of a serious investment in human and material resources. Conclusions: There is a hidden treasure in birth cohorts that deserves to be brought out to study the relationships between employment and health among working parents in a time when the boundaries between work and life are being stretched more than ever before. This paper was written within the scope of OMEGANET, supported by COST (European Cooperation in Science and Technology), project CA16216: Network on the Coordination and Harmonisation of European Occupational Cohorts. Maribel Casas holds a Miguel Servet fellowship (CP16/00128) funded by Instituto de Salud Carlos III and co-funded by European Social Fund “Investing in your future”. We acknowledge support from the Spanish Ministry of Science and Innovation through the “Centro de Excelencia Severo Ochoa 2019-2023” Program (2018-000806-S), and support from the Generalitat de Catalunya through the CERCA Program. Milena Maule’s work was supported by the Compagnia di San Paolo “Bando per il finanziamento ex-post di Progetti di Ricerca di Ateneo – Anno 2018”. Ghislaine Scelo’s work was supported by a LifeCycle fellowship (Grant Agreement No. 733206 LifeCycle). Working life, health and well-being of parents: a joint effort to uncover hidden treasures in European birth cohorts.

Introduction The relationship between allergen exposure to animals in pregnancy and the development of allergic symptoms is not clear. Aim To evaluate the association between prenatal and postnatal exposure to pet ownership and development of atopic dermatitis, food allergy and wheezing in children at the age of 1 and 2. Material and methods The mother-child pairs included in this study were part of the Polish Mother and Child Cohort. Mothers in each trimester of pregnancy and 1 year after childbirth have completed a questionnaire on animal exposure. Children's health status was assessed at around one year and two years of age. Results Keeping a dog at home before and during pregnancy (every trimester) decreased the risk of food allergy in the first year of life. On the other hand, keeping any animal other than a dog (cat, hamster, guinea pig, rabbit) before pregnancy and during each trimester separately increased the risk of food allergy in the first year of life of children. Keeping a guinea pig in the first trimester of pregnancy increased the risk of wheezing in the first year of life. The analysis did not show any significant associations between keeping animals at home before and during pregnancy and the occurrence of atopic dermatitis in the second year of life. Conclusions Keeping a dog at home before and during pregnancy decreased the risk of food allergy in 1-year-old children. This effect was eliminated in case of having a cat, hamster, guinea pig, or rabbit.

RationaleSevere fetal malnutrition has been related to an increased risk of respiratory diseases later in life, but evidence for the association of a suboptimal diet during pregnancy with respiratory outcomes in childhood is conflicting. We aimed to examine whether a pro-inflammatory or low-quality maternal diet during pregnancy was associated with child's respiratory health.MethodsWe performed an individual participant meta-analysis among 18 326 mother–child pairs from seven European birth cohorts. Maternal pro-inflammatory and low-quality diets were estimated by energy-adjusted Dietary Inflammatory Index (E-DII) and Dietary Approaches to Stop Hypertension (DASH) scores. Preschool wheezing and school-age asthma were measured using questionnaires and lung function by spirometry.ResultsAfter adjustment for lifestyle and sociodemographic factors, we observed that a higher maternal E-DII score (a more pro-inflammatory diet) during pregnancy was associated only with a lower forced vital capacity (FVC) in children (z-score difference −0.05, 95% CI −0.08– −0.02, per interquartile range increase). No linear associations of the maternal E-DII or DASH score with child's wheezing or asthma were observed. In an exploratory examination of the extremes, a very low DASH score (ConclusionThe main results from this individual participant data meta-analysis do not support the hypothesis that maternal pro-inflammatory or low-quality diet in pregnancy are related to respiratory diseases in childhood.

Background Bisphenol A (BPA) is an industrial chemical mostly used in the manufacture of plastics, resins and thermal paper. Several studies have reported adverse health effects with BPA exposures, namely metabolic disorders and altered neurodevelopment in children, among others. The aim of this study was to explore BPA exposure, its socio-demographic and life-style related determinants, and its association with neurodevelopmental outcomes in early school age children from Poland. Methods A total of 250 urine samples of 7 year-old children from the Polish Mother and Child Cohort Study (REPRO_PL) were analyzed for BPA concentrations using high performance liquid chromatography with online sample clean-up coupled to tandem mass spectrometry (online-SPE-LC-MS/MS). Socio-demographic and lifestyle-related data was collected by questionnaires or additional biomarker measurements. Emotional and behavioral symptoms in children were assessed using mother-reported Strengths and Difficulties Questionnaire (SDQ). Cognitive and psychomotor development was evaluated by Polish adaptation of the Intelligence and Development Scales (IDS) performed by trained psychologists. Results Urinary BPA concentrations and back-calculated daily intakes (medians of 1.8 μg/l and 46.3 ng/kg bw/day, respectively) were similar to other European studies. Urinary cotinine levels and body mass index, together with maternal educational level and socio-economic status, were the main determinants of BPA levels in Polish children. After adjusting for confounding factors, BPA has been found to be positively associated with emotional symptoms (β: 0.14, 95% CI: 0.022; 0.27). Cognitive and psychomotor development were not found to be related to BPA levels. Conclusions This study represents the first report of BPA levels and their determinants in school age children in Poland. The exposure level was found to be related to child emotional condition, which can have long-term consequences including social functioning and scholastic achievements. Further monitoring of this population in terms of overall chemical exposure is required.

Objectives The objective of this study was to evaluate the association between breastfeeding duration and child neurodevelopment based on the Polish Mother and Child Cohort Study. Material and Methods The current analysis included 501 mother–child pairs. The analysis evaluating the association between the length of breastfeeding and child neurodevelopment considered the following variables: maternal age and body mass index, weight gain during pregnancy, parental level of education, marital status, socioeconomic status, child gender, birthweight, type of delivery, preterm delivery, pre- and postnatal exposure to tobacco constituents and child day care attendance. Psychomotor development was assessed in 1-year-olds on the Bayley Scales of Infant and Toddler Development . Results The length of breastfeeding correlated positively with maternal age at delivery (ρ = 0.13), maternal and paternal level of education (ρ = 0.2 and ρ = 0.14 respectively), birthweight (ρ = 0.1) and marital status (ρ = 0.16) (p < 0.05). A negative correlation between the length of breastfeeding and maternal smoking status during the first year after delivery (ρ = –0.19) and weight gain during pregnancy (r = –0.1) was observed (p < 0.05). The association between the duration of breastfeeding and child development was not statistically significant in the model with the inclusion of confounding variables. A significant association between language development and maternal level of education (p = 0.004), gender of the child (p = 0.0007) and maternal weight gain during pregnancy (p = 0.01) was found. A negative association between cognitive development and maternal salivary cotinine during pregnancy (p = 0.03) and a negative association between motor development and maternal smoking status during the first year after delivery (p = 0.007) were also found. Conclusions This study found no significant association between the duration of breastfeeding and child development after adjustment for confounders. Int J Occup Med Environ Health. 2019;32(2):175–84

Objective: Evidence on the impact of leisure time physical activity (LTPA) in pregnancy on birth size is inconsistent. We aimed to examine the association between LTPA during early and late pregnancy and newborn anthropometric outcomes.Design: Individual level meta‐analysis, which reduces heterogeneity across studies.Setting: A consortium of eight population‐based studies (seven European and one US) comprising 72 694 participants.Methods: Generalised linear models with consistent inclusion of confounders (gestational age, sex, parity, maternal age, education, ethnicity, BMI, smoking, and alcohol intake) were used to test associations between self‐reported LTPA at either early (8–18 weeks gestation) or late pregnancy (30+ weeks) and the outcomes. Results were pooled using random effects meta‐analyses.Main outcome measures: Birth weight, large‐for‐gestational age (LGA), macrosomia, small‐for‐gestational age (SGA), % body fat, and ponderal index at birth.Results: Late, but not early, gestation maternal moderate to vigorous physical activity (MVPA), vigorous activity, and LTPA energy expenditure were modestly inversely associated with BW, LGA, macrosomia, and ponderal index, without heterogeneity (all: I2 = 0%). For each extra hour/week of MVPA, RR for LGA and macrosomia were 0.97 (95% CI: 0.96, 0.98) and 0.96 (95% CI: 0.94, 0.98), respectively. Associations were only modestly reduced after additional adjustments for maternal BMI and gestational diabetes. No measure of LTPA was associated with risk for SGA.Conclusions: Physical activity in late, but not early, pregnancy is consistently associated with modestly lower risk of LGA and macrosomia, but not SGA.Tweetable abstract: In an individual participant meta‐analysis, late pregnancy moderate to vigorous physical activity modestly reduced birth size outcomes.

Exposure to environmental factors, such as neurotoxic metals and micronutrients, during critical periods of development can contribute to long-term consequences in offspring's health, including neurodevelopmental outcomes. The aim of this study was to evaluate the association between simultaneous prenatal exposure to metals [lead (Pb), cadmium (Cd), mercury (Hg)] and micronutrients [selenium (Se), zinc (Zn), copper (Cu)] and neurodevelopmental outcomes in school-age children from the Polish Mother and Child Cohort (REPRO_PL). Metals and micronutrients concentrations were measured in cord blood (Pb, Cd, Se, Zn, Cu) and in maternal hair (Hg) collected during the 3rd trimester of pregnancy. Behavioral and emotional problems, as well as children's cognitive and psychomotor development, were assessed in 436 school-age children using the Strengths and Difficulties Questionnaire (SDQ, filled in by the mothers) and the Polish adaptation of the Intelligence and Development Scales (IDS, administered by trained psychologists). Multivariate regression models were applied after imputation of missing values, using two approaches: (i) a joint analysis taking into account all metals and micronutrients simultaneously, and (ii) an ExWAS study (single-exposure model). In the SDQ, Hyperactivity/Inattention problems and Total difficulties were associated with higher Hg concentrations in maternal hair (0.18, 95% CI: 0.05; 0.3; and 0.14, 95% CI: 0.01; 0.3, respectively), whereas Emotional symptoms were inversely associated with Se and Zn levels in cord blood (−0.13, 95% CI: −0.3; 0.004; and −0.10, 95% CI: −0.2; 0.02, respectively). In the IDS, cord blood Pb levels were found to be negatively associated with Fluid and Crystallized IQ (−0.12, 95% CI: −0.3; 0.02; and −0.14, 95% CI: −0.3; 0.007, respectively) as well as Mathematical skills (−0.15, 95% CI: −0.3; 0.01). The current research has been able to simultaneously assess the exposure to various interacting chemicals during the prenatal period. We demonstrate that prenatal co-exposures to Pb, Hg, Zn and Se have long-term influences on the neuropsychological outcome of school-age children.

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 &lt, 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 (β = 3.1, 95%CI: 0.2–5.9), whereas BMI ≥ 25 kg/m2, and multiparity of a higher copper concentration in plasma (β = 0.2, 95%CI: 0.03-0.4, β = 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 (β = 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.

Background Mounting evidence suggests that maternal diet influences pregnancy and birth outcomes, but its contribution to the global epidemic of childhood obesity has not as yet been definitively characterized. We investigated whether maternal whole diet quality and inflammatory potential influence childhood adiposity. Methods We harmonized and pooled individual participant data from 16,295 mother-child pairs in seven European birth cohorts. Maternal pre-, early-, late-, and whole-pregnancy (any time during pregnancy) dietary quality and inflammatory potential assessed with the Dietary Approaches to Stop Hypertension (DASH) score and the energy-adjusted Dietary Inflammatory Index (E-DII™) score, respectively. Primary outcome was childhood overweight and obesity (OWOB) (age-and-sex-specific BMI z-score > 85th percentile). Secondary outcomes were sum of skinfold thickness (SST), fat mass index (FMI) and fat-free mass index (FFMI). We used multivariable regression analyses (adjusting for maternal lifestyle and sociodemographic factors) to assess the associations of maternal DASH and E-DII scores with offspring adiposity outcomes in cohort-specific analyses, with subsequent random-effect meta-analyses. Results The study mothers had a mean (SD) age of 30.2 (4.6) years and a mean BMI of 23.4 (4.2) kg/m2. Higher early-pregnancy E-DII scores (more pro-inflammatory diet) tended to be associated with a higher odds of late-childhood [10.6 (1.2) years] OWOB [OR (95% CI) 1.09 (1.00, 1.19) per 1-SD E-DII score increase], whereas an inverse association was observed for late-pregnancy E-DII score and early-childhood [2.8 (0.3) years] OWOB [0.91 (0.83, 1.00)]. Higher maternal whole pregnancy DASH score (higher dietary quality) was associated with a lower odds of late-childhood OWOB [OR (95% CI) 0.92 (0.87, 0.98) per 1-SD DASH score increase]; associations were of similar magnitude for early and late-pregnancy [0.86 (0.72, 1.04) and 0.91 (0.85, 0.98), respectively]. These associations were robust in several sensitivity analyses and further adjustment for birth weight and childhood diet did not meaningfully alter the associations and conclusions. In two cohorts with available data, a higher whole pregnancy E-DII and lower DASH scores were associated with a lower late-childhood FFMI in males and a higher mid-childhood FMI in females (P interactions Conclusions A pro-inflammatory, low-quality maternal antenatal diet may adversely influence offspring body composition and OWOB risk, especially during late-childhood. Promoting an overall healthy and anti-inflammatory maternal dietary pattern may contribute to the prevention of childhood obesity, a complex health issue requiring multifaceted strategy.

Background Adverse birth outcomes are major causes of morbidity and mortality during childhood and associate with a higher risk of noncommunicable diseases in adult life. Maternal periconception and antenatal nutrition, mostly focusing on single nutrients or foods, has been shown to influence infant birth outcomes. However, evidence on whole diet that considers complex nutrient and food interaction is rare and conflicting. We aim to elucidate the influence of whole-diet maternal dietary inflammatory potential and quality during periconceptional and antenatal periods on birth outcomes. Methods and findings We harmonized and pooled individual participant data (IPD) from up to 24,861 mother–child pairs in 7 European mother–offspring cohorts [cohort name, country (recruitment dates): ALSPAC, UK (1 April 1991 to 31 December 1992); EDEN, France (27 January 2003 to 6 March 2006); Generation R, the Netherlands (1 April 2002 to 31 January 2006); Lifeways, Ireland (2 October 2001 to 4 April 2003); REPRO_PL, Poland (18 September 2007 to 16 December 2011); ROLO, Ireland (1 January 2007 to 1 January 2011); SWS, United Kingdom (6 April 1998 to 17 December 2002)]. Maternal diets were assessed preconceptionally (n = 2 cohorts) and antenatally (n = 7 cohorts). Maternal dietary inflammatory potential and quality were ranked using the energy-adjusted Dietary Inflammatory Index (E-DII) and Dietary Approaches to Stop Hypertension (DASH) index, respectively. Primary outcomes were birth weight and gestational age at birth. Adverse birth outcomes, i.e., low birth weight (LBW), macrosomia, small-for-gestational-age (SGA), large-for-gestational-age (LGA), preterm and postterm births were defined according to standard clinical cutoffs. Associations of maternal E-DII and DASH scores with infant birth outcomes were assessed using cohort-specific multivariable regression analyses (adjusted for confounders including maternal education, ethnicity, prepregnancy body mass index (BMI), maternal height, parity, cigarettes smoking, and alcohol consumption), with subsequent random-effects meta-analyses. Overall, the study mothers had a mean ± SD age of 29.5 ± 4.9 y at delivery and a mean BMI of 23.3 ± 4.2 kg/m2. Higher pregnancy DASH score (higher dietary quality) was associated with higher birth weight [β(95% CI) = 18.5(5.7, 31.3) g per 1-SD higher DASH score; P value = 0.005] and head circumference [0.03(0.01, 0.06) cm; P value = 0.004], longer birth length [0.05(0.01, 0.10) cm; P value = 0.010], and lower risk of delivering LBW [odds ratio (OR) (95% CI) = 0.89(0.82, 0.95); P value = 0.001] and SGA [0.87(0.82, 0.94); P value < 0.001] infants. Higher maternal prepregnancy E-DII score (more pro-inflammatory diet) was associated with lower birth weight [β(95% CI) = −18.7(−34.8, −2.6) g per 1-SD higher E-DII score; P value = 0.023] and shorter birth length [−0.07(−0.14, −0.01) cm; P value = 0.031], whereas higher pregnancy E-DII score was associated with a shorter birth length [−0.06(−0.10, −0.01) cm; P value = 0.026] and higher risk of SGA [OR(95% CI) = 1.18(1.11, 1.26); P value < 0.001]. In male, but not female, infants higher maternal prepregnancy E-DII was associated with lower birth weight and head circumference, shorter birth length, and higher risk of SGA (P-for-sex-interaction = 0.029, 0.059, 0.104, and 0.075, respectively). No consistent associations were observed for maternal E-DII and DASH scores with gestational age, preterm and postterm birth, or macrosomia and LGA. Limitations of this study were that self-reported dietary data might have increased nondifferential measurement error and that causality cannot be claimed definitely with observational design. Conclusions In this cohort study, we observed that maternal diet that is of low quality and high inflammatory potential is associated with lower offspring birth size and higher risk of offspring being born SGA in this multicenter meta-analysis using harmonized IPD. Improving overall maternal dietary pattern based on predefined criteria may optimize fetal growth and avert substantial healthcare burden associated with adverse birth outcomes., In this cohort analysis, Ling-Wei Chen and colleagues explore associations of maternal dietary patterns with offspring birth outcomes., Author summary Why was this study done? Adverse birth outcomes are associated with higher morbidity and mortality during childhood and a higher risk of noncommunicable diseases in adult life. The Developmental Origins of Health and Diseases (DOHaD) theory posits that maternal periconceptional and intrauterine nutrition can alter the health trajectory of the offspring. Although individual maternal dietary factors have been studied widely, evidence on the impact of whole-diet maternal dietary inflammatory potential and quality on birth outcomes is scarce and conflicting. What did the researchers do and find? We investigated whether maternal prepregnancy and antenatal dietary quality and inflammatory potential are associated with birth outcomes in a consortium of 7 European cohorts in 5 countries using harmonized individual participant data from up to 24,861 mother–child pairs. After adjusting for confounders, we found that a low-quality and pro-inflammatory maternal diet during pregnancy is significantly associated with lower offspring birth weight and higher risk of offspring being born small-for-gestational-age (SGA). In male, but not female, infants higher maternal prepregnancy energy-adjusted Dietary Inflammatory Index (E-DII) score was associated with lower birth weight and head circumference, shorter birth length, and higher risk of SGA. What do these findings mean? Improving overall maternal dietary quality and reducing dietary inflammatory potential may optimize fetal growth and avert substantial healthcare burden associated with adverse birth outcomes. Policies to ensure availability of affordable healthy foods and programmatic efforts to inform and support women of reproductive age, such as raising awareness of the importance of maternal diet and prenatal and antenatal counseling would help women achieve a healthier diet.

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. This work was supported by an award from the European Union’s Horizon 2020 research and innovation programme under the ERA-Net Cofund of the Joint Programming Initiative Healthy Diet for Healthy Life (JPI-HDHL) (http://www.healthydietforhealthylife.eu) action number 696295 (Biomarkers for Nutrition and Health). Cofunding was provided by Science Foundation Ireland, Ireland (Grant No. SFI/16/ERA-HDHL/3360 [to CMP]), the UK Biotechnology and Biological Sciences Research Council (ERA-HDHL Biomarkers: BBSRC BB/P028187/1 [to CR]), the Polish National Centre for Research and Development (ERA-HDHL/01/ALPHABET/1/2017 [to KP]), the ZonMw The Netherlands (Grant No. 529051014; 2017) ALPHABET project (Grant No. 696295; 2017 [to LD]) and the French National Agency of Research (reference AnrR16227KK [to BH]). ALSPAC: This work was supported by the UK Medical Research Council and Wellcome (Grant No. 102215/2/13/2) and the University of Bristol. This publication is the work of the authors and Matthew Suderman will serve as guarantors for the contents of this paper. EDEN: This work was supported by the Foundation for Medical Research (FRM), National Agency for Research (ANR), National Institute for Research in Public health (IRESP: TGIR Cohorte Santé 2008 program), French Ministry of Health (DGS), French Ministry of Research, INSERM Bone and Joint Diseases National Research (PRO-A), and Human Nutrition National Research Programs, Paris-Sud University, Nestlé, French National Institute for Population Health Surveillance (InVS), French National Institute for Health Education (INPES), the European Union FP7 programmes (FP7/2007-2013, HELIX, ESCAPE, ENRIECO, Medall projects), Diabetes National Research Program (through a collaboration with the French Association of Diabetic Patients), French Agency for Environmental Health Safety (now ANSES), Mutuelle Générale de l’Education Nationale, a complementary health insurance (MGEN), French National Agency for Food Security, French-speaking Association for the Study of Diabetes and Metabolism (ALFEDIAM). Generation R: This work was supported by the Erasmus Medical Centre, Rotterdam, the Erasmus University Rotterdam and the Netherlands Organization for Health Research and Development. Dr Liesbeth Duijts received funding from the European Union's Horizon 2020 cofunded programme ERA-Net on Biomarkers for Nutrition and Health (ERA HDHL) (ALPHABET project (Grant No. 696295; 2017), ZonMW The Netherlands (Grant No. 529051014; 2017). Dr. Hanan El Marroun was supported by Stichting Volksbond Rotterdam, the Dutch Brain Foundation (De Hersenstichting, project number GH2016.2.01), and NARSAD Young Investigator Grant No. 27853 from the Brain & Behavior Research Foundation. The project received funding from the European Union’s Horizon 2020 Research and Innovation Programme (LIFECYCLE project, Grant No. 733206; 2016). REPRO_PL: This work was supported by the Ministry of Science and Higher Education, Poland (PBZ-MEiN-/8/2//2006; Contract No. K140/P01/2007/1.3.1.1); by the grant PNRF-218-AI-1/07 from Norway through the Norwegian Financial Mechanism within the Polish-Norwegian Research Fund, National Science Centre under the call of JPI HDHL Nutrition and Cognitive Function (2015/17/Z/NZ7/04273), and the National Science Centre, Poland (DEC-2014/15/B/NZ7/00998). Mònica Guxens (CPII18/00018) and Maribel Casas (CP16/00128) are funded by a Miguel Servet fellowship (from the Spanish Institute of Health Carlos III). We acknowledge support from the Spanish Ministry of Science and Innovation through the “Centro de Excelencia Severo Ochoa 2019–2023” Program (CEX2018-000806-S), and support from the Generalitat de Catalunya through the CERCA Programme.

In this study, the exposome paradigm has been applied on a mother-child cohort adopting an optimised untargeted metabolomics approach for human urine followed by advanced bioinformatics analysis. Exposome-wide association algorithms were used to draw links between in utero co-exposure to metals and phthalates, metabolic pathways deregulation, and clinically observed phenotypes of neurodevelopmental disorders such as problems in linguistic, motor development and cognitive capacity. Children (n = 148) were tested at the first and second year of their life using the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III). Their mothers had been exposed to metals and phthalates during the pregnancy, according to human biomonitoring results from previously performed studies. Untargeted metabolomics analysis of biobanked urine samples from the mothers was performed using a combination of the high throughput analytical methods liquid chromatography-high resolution mass spectrometry (LC-HRMS) and nuclear magnetic resonance (NMR). Most perturbed metabolic pathways from co-exposure heavy metals and phthalates were pathways related to the tricarboxylic acid cycle (TCA cycle) and oxidative phosphorylation, indicating the possibility of disruption of mitochondrial respiration. Overproduction of reactive oxygen species (ROS); the presence of glutathione peroxidase 3 (GPx3) during pregnancy and presence of glutathione peroxidase 1 (GPx1) in the umbilical cord were linked to verbal development problems. Another finding of the study is that in real life, adverse outcomes occur as a combination of environmental and social factors, all of them acting synergistically towards the deployment of an observed phenotype. Finally, the two-steps association process (exposure to pathways and pathways to adverse outcomes) was able to (a) provide associations that are not evident by directly associating exposure to outcomes and (b) provides additional insides on the mechanisms of environmental disease.

The impact of maternal diet during pregnancy on the risk of allergic diseases in childhood is an increasing scientific and public health concern. We evaluated the associations of maternal type of diet and essential elements and vitamins intake during pregnancy with offspring allergic and respiratory outcomes.The study population included 557 mother-child pairs from Polish Mother and Child Cohort (REPRO_PL). Based on the Food Frequency Questionnaire filled in between the 20th-24th week of pregnancy, overall maternal diet was evaluated as the difference between the Prudent Dietary Pattern (PDP) score and Western Dietary Pattern (WDP) score ((PDP-WDP) score) and maternal achievement of dietary recommendations (estimated average requirement, EAR) for essential elements and vitamins was assessed. Children's health examination at age of 1, 2, and 7-9 years covered the following symptoms: infections, wheezing/asthma, food allergy, allergic rhinitis, and atopic dermatitis. At age of 7-9 years, children underwent spirometry and skin-prick tests.Children of the mothers who were not achieving adequate intake of vitamin C during pregnancy had a higher risk of wheezing and having more than two infections within the first two years of life comparing to those who met EAR (OR = 2.6, p = 0.05, and OR = 2.3, p = 0.04, respectively). Inadequate intake of vitamin E during pregnancy was related to a higher risk of atopic dermatitis (OR = 2.7, p = 0.04), whereas inadequate intake of magnesium during pregnancy was associated with the risk of wheezing in the offspring at age of two years (OR = 3.7, p = 0.03). A lower (PDP-WDP) score during pregnancy (indicating unhealthier diet) was associated with a higher risk of infections (OR = 1.5, p = 0.007) but a lower risk of atopic dermatitis (OR = 0.7, p = 0.02) at age of 7-9 years.These results may contribute to the body of evidence for the impact of maternal diet during pregnancy for children's optimal health, however further studies are needed before drawing conclusions and recommendations for clinical practice.

Background: Fetal exposure to a suboptimal maternal diet might affect respiratory health later in life. We tested the hypothesis that a pro-inflammatory or low-quality maternal diet in pregnancy was associated with child’s respiratory health. Methods: We performed an individual participant meta-analysis among 18,326 children and their mothers, participating in seven European birth cohorts. Maternal pro-inflammatory diet during pregnancy was estimated by the energy-adjusted Dietary Inflammatory Index score (E-DIITM), and low quality diet by the Dietary Approaches to Stop Hypertension (DASH) score. Child’s preschool wheezing and school-age asthma and lung function were measured by questionnaires and spirometry. We used multilevel regression models with a random intercept at cohort level to study the associations. Results: After adjustment for lifestyle and sociodemographic factors, we observed no consistent associations of a high E-DII score (>90th percentile) with respiratory outcomes, but a low DASH score ( Conclusion: A low quality maternal diet in pregnancy might have a modest adverse effect on respiratory health in childhood.

Background Fetal smoke exposure is a common and key avoidable risk factor for birth complications and seems to influence later risk of overweight. It is unclear whether this increased risk is also present if mothers smoke during the first trimester only or reduce the number of cigarettes during pregnancy, or when only fathers smoke. We aimed to assess the associations of parental smoking during pregnancy, specifically of quitting or reducing smoking and maternal and paternal smoking combined, with preterm birth, small size for gestational age, and childhood overweight. Methods and findings We performed an individual participant data meta-analysis among 229,158 families from 28 pregnancy/birth cohorts from Europe and North America. All 28 cohorts had information on maternal smoking, and 16 also had information on paternal smoking. In total, 22 cohorts were population-based, with birth years ranging from 1991 to 2015. The mothers’ median age was 30.0 years, and most mothers were medium or highly educated. We used multilevel binary logistic regression models adjusted for maternal and paternal sociodemographic and lifestyle-related characteristics. Compared with nonsmoking mothers, maternal first trimester smoking only was not associated with adverse birth outcomes but was associated with a higher risk of childhood overweight (odds ratio [OR] 1.17 [95% CI 1.02–1.35], P value = 0.030). Children from mothers who continued smoking during pregnancy had higher risks of preterm birth (OR 1.08 [95% CI 1.02–1.15], P value = 0.012), small size for gestational age (OR 2.15 [95% CI 2.07–2.23], P value < 0.001), and childhood overweight (OR 1.42 [95% CI 1.35–1.48], P value < 0.001). Mothers who reduced the number of cigarettes between the first and third trimester, without quitting, still had a higher risk of small size for gestational age. However, the corresponding risk estimates were smaller than for women who continued the same amount of cigarettes throughout pregnancy (OR 1.89 [95% CI 1.52–2.34] instead of OR 2.20 [95% CI 2.02–2.42] when reducing from 5–9 to ≤4 cigarettes/day; OR 2.79 [95% CI 2.39–3.25] and OR 1.93 [95% CI 1.46–2.57] instead of OR 2.95 [95% CI 2.75–3.15] when reducing from ≥10 to 5–9 and ≤4 cigarettes/day, respectively [P values < 0.001]). Reducing the number of cigarettes during pregnancy did not affect the risks of preterm birth and childhood overweight. Among nonsmoking mothers, paternal smoking was associated with childhood overweight (OR 1.21 [95% CI 1.16–1.27], P value < 0.001) but not with adverse birth outcomes. Limitations of this study include the self-report of parental smoking information and the possibility of residual confounding. As this study only included participants from Europe and North America, results need to be carefully interpreted regarding other populations. Conclusions We observed that as compared to nonsmoking during pregnancy, quitting smoking in the first trimester is associated with the same risk of preterm birth and small size for gestational age, but with a higher risk of childhood overweight. Reducing the number of cigarettes, without quitting, has limited beneficial effects. Paternal smoking seems to be associated, independently of maternal smoking, with the risk of childhood overweight. Population strategies should focus on parental smoking prevention before or at the start, rather than during, pregnancy., Elise Philips and co-workers investigate parental smoking and associated birth and child outcomes., Author summary Why was this study done? Maternal smoking during pregnancy is an important risk factor for various birth complications and childhood overweight. It is not clear whether this increased risk is also present if mothers smoke during the first trimester only or reduce the number of cigarettes during pregnancy. The associations of paternal smoking with birth and childhood outcomes also remain unknown. What did the researchers do and find? We conducted an individual participant data meta-analysis using data from 229,158 families from 28 pregnancy and birth cohorts from Europe and North America to assess the associations of parental smoking during pregnancy, specifically of quitting or reducing smoking and maternal and paternal smoking combined, with preterm birth, small size for gestational age, and childhood overweight. We observed that smoking in the first trimester only did not increase the risk of preterm birth and small size for gestational age but was associated with a higher risk of childhood overweight, as compared to nonsmoking. Reducing the number of cigarettes during pregnancy, without quitting, was still associated with higher risks of these adverse outcomes. Paternal smoking seems to be associated, independently of maternal smoking, with the risks of childhood overweight. What do these findings mean? Population strategies should focus on parental smoking prevention before or at the start of, rather than during, pregnancy. Future studies are needed to assess the specific associations of smoking in the preconception and childhood periods with offspring outcomes.

Purpose: Based on the available data, alterations of the antioxidant defense as well as the vitamin status in mothers may affect the prenatal process of lung and immune system development as a pathophysiological background of increased prevalence of allergic diseases. The primary aim of the current study was to assess the associations among cord blood concentrations of zinc (Zn); copper (Cu); selenium (Se); β-carotene; and vitamin A, E, and D, and the occurrence of atopic dermatitis, food allergy, allergic rhinitis, and asthma in early school-age children. Methods: We evaluated 211 children, 7‐9 years old, from the Polish Mother and Child Cohort Study. the women were interviewed during pregnancy to collect demographic and socioeconomic data, and the medical and reproductive history. At delivery, umbilical cord blood plasma was sampled. Seven to nine years after the birth, the child's exposure and health status (including skin-prick test and spirometry for allergy assessment and urine sample for cotinine level) were examined. In the analyses, a multivariable model was applied. Results: Statistically significant relationships were found among Zn; Cu; Se; and vitamin A, E, and D concentrations in cord blood; and the prevalence of food allergy, allergic rhinitis, atopic dermatitis, and asthma in children ages 7‐9 years after adjustment for several confounders. Conclusion: We showed an imbalance in the antioxidant defense system in cord blood, which may lead to the occurrence of allergic diseases later in life. The maternal diet may have substantial potential to modify immune tolerance and, consequently, the development of allergic disease in the offspring.Clinical trial NCT01861548, www.clinicaltrials.gov

Aim A growing body of literature documents associations between maternal stress in pregnancy and child development, but findings across studies are often inconsistent. The aim of this study was to estimate the association between exposure to different kinds of prenatal stress and child psychomotor development. Methods The study population consisted of 372 mother-child pairs from Polish Mother and Child Cohort. The analysis was restricted to the women who worked at least 1 month during pregnancy period. Maternal psychological stress during pregnancy was assessed based on: the Subjective Work Characteristics Questionnaire, Perceived Stress Scale and Social Readjustment Rating Scale. The level of satisfaction with family functioning and support was evaluated by APGAR Family Scale. Child psychomotor development was assessed at the 12th and 24th months of age by Bayley Scales of Infant and Toddler Development. Results Negative impact on child cognitive development at the age of two was observed for the Perceived Stress Scale (β = −0.8; P = 0.01) and the Social Readjustment Rating Scale (β = −0.4; P = 0.03) after adjusting for the variety of confounders. Occupational stress, as well as satisfaction with family functioning, was not significantly associated with child psychomotor development (P > 0.05). Conclusions The study supports the findings that prenatal exposure to maternal stress is significantly associated with decreased child cognitive functions. In order to further understand and quantify the effects of prenatal stress on child neurodevelopment further studies are needed. This will be important for developing interventions that provide more assistance to pregnant women, including emotional support or help to manage psychological stress.

Micronutrients status during pregnancy is recognized as one of the environmental factors that can have an impact on maternal and children’s health. The study aims at evaluating sociodemographic, lifestyle, environmental, and pregnancy-related determinants of maternal micronutrients status during pregnancy. The analysis was based on data 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) based on which the intake of the following micronutrients was estimated: calcium, magnesium, zinc, copper, selenium, folate, vitamin D, vitamin A and vitamin E. In addition, copper, zinc and selenium levels were measured in the blood collected during the second trimester of pregnancy. About 95% of the women took dietary supplements during pregnancy. Despite such supplementation in the case of a high proportion of the women the intake of majority of the analyzed micronutrients was below recommendations for the pregnancy period (based on the Estimated Average Requirement). The mean plasma zinc, copper and selenium concentrations were 0.9±0.3 mg/l, 2.0±0.6 mg/l and 48.4±10.5 ug/l, respectively. The chance to reach the recommended intake for vitamin A, vitamin D and selenium was higher among the multiparous women (OR = 1.53 p = 0.007; OR = 1.44 p = 0.02; OR = 1.48 p = 0.009) and for zinc among the women with a higher socio-economic status (SES) (OR = 1.43 p = 0.04). For other variables the results were not statistically significant. A higher selenium level in the plasma was observed among the older women (p = 0.01) and those with a higher SES (p = 0.03). The current study presents evidence on specific factors influencing the micronutrients intake. They need to be accounted for in educational programs and interventions that focus on healthy diet recommendations during pregnancy. Key messages In the case of a high proportion of the women the intake of majority of the analyzed micronutrients was below recommendations for the pregnancy period. More effort should be taken to educational programs and interventions that focus on healthy diet recommendations during pregnancy.

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: β = −5.2; p = 0.006; β = −4.2; p = 0.006; mono-n-butyl phthalate (MnBP): β = −4.9; p = 0.03; β = −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): β = 3.6; p = 0.03 for fluid intelligence; β = 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.

Characterization of the exposome, the totality of all environmental factors that one is exposed to from conception onwards, has been recommended to better evaluate the role of environmental influences on developmental programming and life- course vulnerability to major chronic diseases. In the framework of the Health and Environment- wide Associations based on Large population Surveys (HEALS) project we considered the pregnancy exposome exploiting two databases (PRIME and REPRO PL) that include birth cohorts from three EU countries (Croatia, Slovenia and Poland). The databases contained information on several chemical exposures, socio-demographic, lifestyle and health related factors from conception to child birth, and neuropsychological scores assessed by the Bayley Scales of Infant and Toddler Development in the first two years of life. Our main goal was to assess consistency of environmental influences on neurodevelopment, if any, across European countries differing for geographical, socio-demographic characteristics and levels of chemical exposures to metals such as lead (Pb), mercury (Hg), cadmium (Cd) and trace elements, including micronutrients such as zinc (Zn) and selenium (Se). To this aim, we first selected variables common to the different databases, then applied univariate and multivariate regression analyses to identify factors linked to neurodevelopment, and finally performed meta-analysis to detect potential heterogeneity among cohorts and pooled estimates. Significant differences in exposure levels among the three sub-cohorts were observed as for Hg and Se ; exposure levels under study were relatively low and within the range described in existing EU biomonitoring studies. The univariate analyses did not show any common pattern of association as only in the Polish cohort chemical exposure had an impact on neuropsychological outcome. In the meta-analysis, some consistent trends were evident, relative to the adverse influence of Pb on children's language and cognition and the positive influence of Se on language abilities. The effects of the neurotoxic metal Hg positively influenced the motor scores in the Polish cohorts, while it decreased the motor scores in the Slovenia and Croatian sub-cohorts. The only socio-demographic factor consistently associated to the outcome among cohorts was child's sex, with females performing better than males on cognitive and language scores. These findings point to the need of harmonizing existing cohorts or creating prospective study designs that facilitate comparisons in the exposome over time, places and kind of environmental exposures.

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. Keywords: Birth cohort, Children, Daily intake, Hazard risk, Phthalate metabolites, Poland

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 (&beta, = 0.2, p &lt, 0.01), higher educational level (&beta, = 0.3, 0.01), and socioeconomic status (SES) (&beta, 0.01), overweight/obesity before (&beta, 0.01), as well as physical activity during pregnancy (&beta, p = 0.01) were positive determinants of a healthier diet (increasing Prudent&ndash, Western difference in dietary pattern scores). On the other hand, parity (&beta, = &minus, 0.2, p = 0.04) and living in small cities (&beta, 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.

Importance: Both low and high gestational weight gain have been associated with adverse maternal and infant outcomes, but optimal gestational weight gain remains uncertain and not well defined for all prepregnancy weight ranges. Objectives: To examine the association of ranges of gestational weight gain with risk of adverse maternal and infant outcomes and estimate optimal gestational weight gain ranges across prepregnancy body mass index categories. Design, setting, and participants: Individual participant-level meta-analysis using data from 196 670 participants within 25 cohort studies from Europe and North America (main study sample). Optimal gestational weight gain ranges were estimated for each prepregnancy body mass index (BMI) category by selecting the range of gestational weight gain that was associated with lower risk for any adverse outcome. Individual participant-level data from 3505 participants within 4 separate hospital-based cohorts were used as a validation sample. Data were collected between 1989 and 2015. The final date of follow-up was December 2015. Exposures: Gestational weight gain. Main outcomes and measures: The main outcome termed any adverse outcome was defined as the presence of 1 or more of the following outcomes: preeclampsia, gestational hypertension, gestational diabetes, cesarean delivery, preterm birth, and small or large size for gestational age at birth. Results: Of the 196 670 women (median age, 30.0 years [quartile 1 and 3, 27.0 and 33.0 years] and 40 937 were white) included in the main sample, 7809 (4.0%) were categorized at baseline as underweight (BMI

Background: The association between air pollution exposure and emotional and behavioural problems in children is unclear. We aimed to assess prenatal and postnatal exposure to several air pollutants and child's depressive and anxiety symptoms, and aggressive symptoms in children of 7-11 years. Methods: We analysed data of 13182 children from 8 European population-based birth cohorts. Concentrations of nitrogen dioxide (NO2), nitrogen oxides (NOx), particulate matter (PM) with diameters of

Background Maternal obesity and excessive gestational weight gain may have persistent effects on offspring fat development. However, it remains unclear whether these effects differ by severity of obesity, and whether these effects are restricted to the extremes of maternal body mass index (BMI) and gestational weight gain. We aimed to assess the separate and combined associations of maternal BMI and gestational weight gain with the risk of overweight/obesity throughout childhood, and their population impact. Methods and findings We conducted an individual participant data meta-analysis of data from 162,129 mothers and their children from 37 pregnancy and birth cohort studies from Europe, North America, and Australia. We assessed the individual and combined associations of maternal pre-pregnancy BMI and gestational weight gain, both in clinical categories and across their full ranges, with the risks of overweight/obesity in early (2.0–5.0 years), mid (5.0–10.0 years) and late childhood (10.0–18.0 years), using multilevel binary logistic regression models with a random intercept at cohort level adjusted for maternal sociodemographic and lifestyle-related characteristics. We observed that higher maternal pre-pregnancy BMI and gestational weight gain both in clinical categories and across their full ranges were associated with higher risks of childhood overweight/obesity, with the strongest effects in late childhood (odds ratios [ORs] for overweight/obesity in early, mid, and late childhood, respectively: OR 1.66 [95% CI: 1.56, 1.78], OR 1.91 [95% CI: 1.85, 1.98], and OR 2.28 [95% CI: 2.08, 2.50] for maternal overweight; OR 2.43 [95% CI: 2.24, 2.64], OR 3.12 [95% CI: 2.98, 3.27], and OR 4.47 [95% CI: 3.99, 5.23] for maternal obesity; and OR 1.39 [95% CI: 1.30, 1.49], OR 1.55 [95% CI: 1.49, 1.60], and OR 1.72 [95% CI: 1.56, 1.91] for excessive gestational weight gain). The proportions of childhood overweight/obesity prevalence attributable to maternal overweight, maternal obesity, and excessive gestational weight gain ranged from 10.2% to 21.6%. Relative to the effect of maternal BMI, excessive gestational weight gain only slightly increased the risk of childhood overweight/obesity within each clinical BMI category (p-values for interactions of maternal BMI with gestational weight gain: p = 0.038, p < 0.001, and p = 0.637 in early, mid, and late childhood, respectively). Limitations of this study include the self-report of maternal BMI and gestational weight gain for some of the cohorts, and the potential of residual confounding. Also, as this study only included participants from Europe, North America, and Australia, results need to be interpreted with caution with respect to other populations. Conclusions In this study, higher maternal pre-pregnancy BMI and gestational weight gain were associated with an increased risk of childhood overweight/obesity, with the strongest effects at later ages. The additional effect of gestational weight gain in women who are overweight or obese before pregnancy is small. Given the large population impact, future intervention trials aiming to reduce the prevalence of childhood overweight and obesity should focus on maternal weight status before pregnancy, in addition to weight gain during pregnancy., Vincent Jaddoe and colleagues report that a high BMI before pregnancy, rather than excessive gestational weight gain, is more likely to contribute to childhood obesity., Author summary Why was this study done? Maternal pre-pregnancy obesity and excessive gestational weight gain are important risk factors of various pregnancy and birth complications. An accumulating body of evidence suggests that maternal obesity and excessive gestational weight gain also have persistent effects on offspring fat development. It is not clear whether these effects exist across the full ranges of maternal pre-pregnancy body mass index and gestational weight gain, what their combined effects are, and what the population impact of these effects is. What did the researchers do and find? We conducted an individual participant data meta-analysis using data from 162,129 mothers and their children from 37 pregnancy and birth cohorts from Europe, North America, and Australia to assess the separate and combined associations of maternal pre-pregnancy body mass index and gestational weight gain with the risk of overweight/obesity throughout childhood, and their population impact. We observed not only that maternal pre-pregnancy overweight and obesity were associated with an increased risk of childhood overweight/obesity, but that this risk increased gradually over the full range of maternal BMI. Similarly, the risk of childhood overweight/obesity increased across the full range of gestational weight gain. We estimated that 21.7% to 41.7% of childhood overweight/obesity prevalence could be attributed to maternal overweight and obesity together, whereas 11.4% to 19.2% could be attributed to excessive gestational weight gain. The additional effect of excessive gestational weight gain on the risk of childhood overweight/obesity was small among women who are already overweight or obese before pregnancy. What do these findings mean? Maternal pre-pregnancy BMI and, to a smaller extent, gestational weight gain are important modifiable risk factors of childhood overweight/obesity with considerable population impact. Future intervention trials aiming to reduce the prevalence of childhood overweight and obesity should focus on maternal weight status before pregnancy, in addition to weight status during pregnancy.

ObjectiveTo assess the separate and combined associations of maternal pre‐pregnancy body mass index (BMI) and gestational weight gain with the risks of pregnancy complications and their population impact.DesignIndividual participant data meta‐analysis of 39 cohorts.SettingEurope, North America, and Oceania.Population265 270 births.MethodsInformation on maternal pre‐pregnancy BMI, gestational weight gain, and pregnancy complications was obtained. Multilevel binary logistic regression models were used.Main outcome measuresGestational hypertension, pre‐eclampsia, gestational diabetes, preterm birth, small and large for gestational age at birth.ResultsHigher maternal pre‐pregnancy BMI and gestational weight gain were, across their full ranges, associated with higher risks of gestational hypertensive disorders, gestational diabetes, and large for gestational age at birth. Preterm birth risk was higher at lower and higher BMI and weight gain. Compared with normal weight mothers with medium gestational weight gain, obese mothers with high gestational weight gain had the highest risk of any pregnancy complication (odds ratio 2.51, 95% CI 2.31– 2.74). We estimated that 23.9% of any pregnancy complication was attributable to maternal overweight/obesity and 31.6% of large for gestational age infants was attributable to excessive gestational weight gain.ConclusionsMaternal pre‐pregnancy BMI and gestational weight gain are, across their full ranges, associated with risks of pregnancy complications. Obese mothers with high gestational weight gain are at the highest risk of pregnancy complications. Promoting a healthy pre‐pregnancy BMI and gestational weight gain may reduce the burden of pregnancy complications and ultimately the risk of maternal and neonatal morbidity.Tweetable abstractPromoting a healthy body mass index and gestational weight gain might reduce the population burden of pregnancy complications.

BACKGROUND: The studies on the impact of selenium (Se) levels in different pregnancy periods on child psychomotor functions are limited. The aim of this study was to evaluate the impact of prenatal Se on child neurodevelopment. METHODS: The study population consisted of 410 mother-child pairs from Polish Mother and Child Cohort. Se levels were measured in each trimester of pregnancy, at delivery, and in cord blood by graphite furnace atomic absorption spectrometry. Psychomotor development was assessed in children at the age of 1 and 2 y using the Bayley Scales of Infant and Toddler Development. RESULTS: Plasma Se levels decreased through pregnancy (from 48.3 ± 10.6 µg/l in the first trimester to 38.4 ± 11.8 µg/l at delivery; P < 0.05). A statistically significant positive association between Se levels in the first trimester of pregnancy and motor development (β = 0.2, P = 0.002) at 1 y of age, and language development (β = 0.2, P = 0.03) at 2 y of age was observed. The positive effect of Se levels on cognitive score at 2 y of age was of borderline significance (β = 0.2, P = 0.05). CONCLUSION: Prenatal selenium status was associated with child psychomotor abilities within the first years of life. Further epidemiological and preclinical studies are needed to confirm the association and elucidate the underlying mechanisms of these effects.

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&rsquo, s neurodevelopment, the Bayley Scales of Infant and Toddler Development was applied. The geometric mean (GM) for blood lead level during 20&ndash, 24 weeks of pregnancy was 0.99 &plusmn, 0.15 &micro, g/dL and, in the cord blood, it was 0.96 &plusmn, 0.16 &micro, g/dL. There was no statistically significant impact of lead exposure during prenatal period on the girls&rsquo, psychomotor abilities. Among the boys, we observed lower scores for cognitive functions, along with increasing cord blood lead levels (&beta, = &minus, 2.07, p = 0.04), whereas the results for the language and motor abilities were not statistically significant (p &gt, 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.

Background: Exposure to air pollution during pregnancy may increase several behavior problems, including depression/anxiety or conduct/aggressive problems in children, but findings have been incons...

Epidemiological studies have suggested an association between maternal antioxidant levels during pregnancy and development of allergic diseases in their offspring. The aim of the study was to determine plasma vitamins A and E concentration in the 1st trimester of pregnancy, at delivery and in cord blood and to search for a relationship with allergy in up to 2-year-old children who were prenatally exposed or not exposed to tobacco smoke. The study participants included 252 mother-child pairs from Polish Mother and Child Cohort. Vitamin concentrations were measured using the HPLC-UV method, smoking status&mdash, as saliva cotinine level using the HPLC-MS/MS technique. Children&rsquo, s health status was assessed using a questionnaire and pediatricians/allergists examination. Cord plasma vitamin concentrations were significantly lower than their levels in maternal plasma in the 1sttrimester and at delivery (p &lt, 0.001). Significantly higher concentrations of vitamin E have been shown to occur during the 1st trimester of pregnancy in plasma of the women who have actively/passively smoked cigarettes compared to the non-smokers (p &lt, 0.02). Multivariate analysis with inclusion of a variety of confounding factors have not indicated any statistically significant associations between &beta, carotene, vitamins A and E and the risk of food allergy, atopic dermatitis and wheezing in their children up to 2 years of age. The interaction between smoking during pregnancy and vitamins levels on the risk of allergy was not statistically significant (p &lt, 0.4). The relationship between plasma concentration of vitamins A and E, and the risk of allergy in their young children has not been demonstrated.

BackgroundGestational weight gain differs according to pre-pregnancy body mass index and is related to the risks of adverse maternal and child health outcomes. Gestational weight gain charts for women in different pre-pregnancy body mass index groups enable identification of women and offspring at risk for adverse health outcomes. We aimed to construct gestational weight gain reference charts for underweight, normal weight, overweight, and grades 1, 2 and 3 obese women and to compare these charts with those obtained in women with uncomplicated term pregnancies.MethodsWe used individual participant data from 218,216 pregnant women participating in 33 cohorts from Europe, North America, and Oceania. Of these women, 9065 (4.2%), 148,697 (68.1%), 42,678 (19.6%), 13,084 (6.0%), 3597 (1.6%), and 1095 (0.5%) were underweight, normal weight, overweight, and grades 1, 2, and 3 obese women, respectively. A total of 138, 517 women from 26 cohorts had pregnancies with no hypertensive or diabetic disorders and with term deliveries of appropriate for gestational age at birth infants. Gestational weight gain charts for underweight, normal weight, overweight, and grade 1, 2, and 3 obese women were derived by the Box-Cox t method using the generalized additive model for location, scale, and shape.ResultsWe observed that gestational weight gain strongly differed per maternal pre-pregnancy body mass index group. The median (interquartile range) gestational weight gain at 40weeks was 14.2kg (11.4-17.4) for underweight women, 14.5kg (11.5-17.7) for normal weight women, 13.9kg (10.1-17.9) for overweight women, and 11.2kg (7.0-15.7), 8.7kg (4.3-13.4) and 6.3kg (1.9-11.1) for grades 1, 2, and 3 obese women, respectively. The rate of weight gain was lower in the first half than in the second half of pregnancy. No differences in the patterns of weight gain were observed between cohorts or countries. Similar weight gain patterns were observed in mothers without pregnancy complications.ConclusionsGestational weight gain patterns are strongly related to pre-pregnancy body mass index. The derived charts can be used to assess gestational weight gain in etiological research and as a monitoring tool for weight gain during pregnancy in clinical practice., ABCDr This work was supported by the Netherlands Organization for Health Research and Development (ZonMw) (TOP grant, 40-00812-98-11010).r ALSPACr The UK Medical Research Council and Wellcome (Grant ref.: 102215/2/13/2) and the University of Bristol provide core support fog ALSPAC. This study has received support from the US National Institute of Health (R01 DK10324) and European Research Council under the European Union's Seventh Framework Programme (FP7/2007-2013)/ERC grant agreement no 669545. DA Lawlor works in a unit that receives UK MRC funding (MQ_UU_12013/5) and is an NIHR senior investigator (NF-Sl-0611-10196).r AOB/Fr All Our Families is funded through Alberta Innovates Interdisciplinary Team Grant 4200700595, the Alberta Children's Hospital Foundation, and the Max Bell Foundation.r DNBCr The Danish National Research Foundation has established the Danish Epidemiology Science Centre that initiated and created the Danish National Birth Cohort. The cohort is furthermore a result of a major grant from this foundation. Additional support for the Danish National Birth Cohort is obtained from the Pharmacy Foundation, the Egmont Foundation, the March of Dimes Birth Defects Foundation, the Augustinus Foundation, and the Health Foundation. The DNBC 7-year follow-up is supported by the Lundbeck Foundation (195/04) and the Danish Medical Research Council (SWF 0646).r EDENr The EDEN Study was supported by Foundation for medical research (FRM), National Agency for Research (ANR), National Institute for Research in Public health (IRESP: TGIR cohorte sante 2008 program), French Ministry of Health (DGS), French Ministry of Research, INSERM Bone and Joint Diseases National Research (PRO-A) and Human Nutrition National Research Programs, Paris-Sud LJniversity, Nestle, French National Institute for Population Health Surveil lance (InVS), French National Institute for h-lealth Education (APES), the European Union FP7 programmes (FP7/2007-2013, HELIX, ESCAPE, ENRIECO, Medall projects), Diabetes National Re.search Program (through a collaboration with the French Association of Diabetic Patients (AFD)), French Agency for Environmental Health Safety (now ANSES), Mutuelle Generale de l'Education Nationale a complementary health inswance (MGEN), French national agency for food security, French-speaking association for the study of diabetes and metabolism (ALFEDIAM).r FCOUr FCOU study is supported by the US National Institutes of Health Fogarty International Center, US NIEHS, US CDC, US PA, and National Academy of Medical Sciences of Ukraine.r GASPIIr Ministry of Health.r GECKO Drenther The GECKO Drenthe birth cohort was funded by an unrestricted grant of Hutchison Whampoa Ld, Hong Kong and supported by the University of Groningen, Well Baby Clinic Foundation Icare, Noodlease, Paediatric Association Of The Netherlands and Youth Health Care Drenthe.r Generation Rr The general design of the Generation R Study is made possible by financial support from the Erasmus MC, University Medical Center, Rotterdam, Erasmus University Rotterdam, Netherlands Organization for Health Research and Development (ZonMw), Netherlands Organisation for Scientific Research (NWO), Ministry of Health, Welfare and Sport and Ministry of Youth and Families. Research leading to these results has received funding from the European Union's Seventh Framework Programme (FP7/2007-2013), project ErlyNutrition under grant agreement no. 289346, the European Union's Horizon 2020 research and innovation programme under grant agreement no.; 633595 (DynalHEALTH)and the European Union's Horzon 2020 research and Innovation programme under grant agreement 733206 (LifeCycle Project). Romy Gaillard received funding from the Dutch Heart Foundation (grant number 2017T013) and the Dutch Diabetes Foundation (grant number 2017.81.002). Vincent Jaddoe received grants from the Netherlands Organization for Health Research and Development (VIDI 016.136.361) and the European Research Council (Consolidator Grant, ERC-2014-CoG-648916).r Generation XXIr Generation XX: was funded by Pmgrama Operational de Saude-Saude XXI, Quadro Comunitario de Apoio III and Administracao Regional de Saude Norte (Regional Department of Ministry of Health). This study was funded by FEDER through the Operational Programme Competitiveness and Internationalization and national funding from the Foundation for Science and Technology FCT (Portuguese Minstry of Science, Technology and Higher Education) (POCI-01-0145-FEDER-016837), under the project PathMOB.: Risco cardiomwtabolico na infancia: desde o inicio da vida ao fim da infancia (Ref. FCT PIDc/DTP-EP1/3306/2014) and the Unidade de Investigacao em Epiclemiologia-Instituto de Saude Publica da Universidade do Porte (EPIUnit) (POCI-01-0145-FEDER-006862; Ref. UlD/DTP/04750/2013). AC Santos holds a FG Investigator contract IF/01060/2015.r GENESISr The study was supported by a research grant from Friesland Foods Hellas. Gen3G Gen3G was supported by a Fonds de recherche du Quebec en sante (FRQ-S) operating grant (grant 4206971; a Canadian Institute of Health Reseach (CIHR) Operating grant (grant WOE) 115071); a Diabete Quebec grant and a Canadian Diabetes Association operating grant (grant #OG-3-08-2622-JA).r GINIplusr The GINIplus study was mainly supported for the first 3 years of the Federal Ministry for Education, Science, Research and Technology I:interventional arm) and Helmholtz Zentrum Munich (former GSF) (observational arm). The 4-year, 6-year, 10-year, and 15-year follow-up examinations of the GINIplus Study were covered from the respective budgets of the 5 study centers Helmoltz Zentrum Munich (former GSF), Research Institute at Marien-Hospital Wesel, LMU Munich, TU Munich and from 6 years onwards also from IUF-Leibniz Research-Institute for Environmental Medicine at the University of Dusseldorp and a grant from the Federal Ministry for Environment (IUF Dus seldoit FKZ 20462296). Further, the 15 year follow-up examination of the GINIplus study was supported by the Commission of the European Communities, the 7th Framework Program: MeDALL project, and as well by the companies Mead Johnson and Nestle.r HUMISr European Community's Seventh Framework Programme (P7/2007-2013) under grant agreements Early Nutrition no. 289346 and by funds from the Norwegian Research Council's MILPAAHEL programme, project no. 213148. INMA-Sabadellr This study was funded by grants from the Institute de Salad Carlos III (Red INMA G03/176) and the Genera tat de Catalunya-CIRIT (1999SGR 00241).r INMA-Valenciar This study was funded by Grants from UE (P7-ENV-2011 cod 282957 and HEALTH2010.2.4.5-1), Spain: ISCIII (G03/176; FIS-FEDER: P109/02647, PI11/01007, PI11/02591, PI11/02038, PI1.3/1944-, PI13/2032, P114/00891, PI14/01687, and PI16/1288; Miguel Servet-FEDER CP11/00178, CP15/00025, and CPII16/00051), and Generalitat Valenciana: FISABIO (UGP 15-230, UGP-15-244, and UGP-15-249).r INMA-Gipuzkoar This study was funded by grants from the Institute. de Salad Carlos III (Red INMA G03/176).; r KOALAr Data collection for the KOALA study from pregnancy up to age 1 year was financially supported by grants from Royal Friesland Foods (Leeuwarden); Trio dos Foundation (Zeist); Phoenix Foundation; Raphael Foundation; Iona Foundation, Foundation for the Advancement of Heilpedagogie (all in the Netherlands).r Krakow Cohortr The study received funding from a NIEHS R01 grants entitled: Vulnerability of the Fetus/Infant to PAH, PM2.5 and FTS and Developmental effects of early-life exposure to airborne PAC (R01ES010165 and R01ES015282) and from The Lundin Foundation, The John and Wendy Neu Family Foundation, The Gladys and Roland Harriman Foundation and an Anonymous Foundation.r LISAplusr The LISAplus study was mainly supported by grants from the Federal Ministry for Education Science, Research and Technology and in addition from Helmholtz Zentrum Munich (former GSF), Helmholtz Centre for Environmental Research-UFZ, Leipzig, Research Institute at Marien-Hospital Wesel, Pediatric Practice, Bad Honnef for the first 2 years. The 4-year, 6-year, 10-year, and 15-year follow-up examinations of the LISA-plus Study were covered from the respective budgets of the involved partners (Helmholtz Zentrum Munich (former GSF), Helmholtz Centre for Enironmental Research-UFZ, Leipzig, Research Institute at Marien-Hospital Wesel Pediatric Practice, Bad Honnef, IUr-Leibniz-Research Institute for Environmental Medicine at the University of Dusseldorf) and in addition by a grant from the Federal Ministry for Environment (IUF-Dussedorf, FKZ 204622961. Further, the 15-year follow-up examination of the LISAplus study was supported by the Commission of the FaMpean Communities and the 7th Framework Program: McDALL project.r LUKAS The grants from the Academy of Finland (grants 139021;287675); the Juho Vainio Foundation; the Foundation for Pediatric Research; EVE/VTR-funding; Paivikki and Saran Sohlberg Foundation; The Finnish Cultural Foundation; European Union QLK4-CT-2001-00250; and by the National Institute for Health and Welfare, Finland.r MoBar The Norwegian Mother and Child Cohort Study is supported by the Norwegian [Ministry of Health and Care. Services and the Ministry of Education and Research, NIH/NIEHS (contract no. N01-ES-75558), NIH/NINDS (grant. no. 1 UO1 NS 047537-01 and grant no. 2 UO1 NS 047537-06A1).r NINFEAr The NINFEA cohort was partially funded by the Compagnia San Paolo Fundation and by the Piedmont Region.r PELAGIEr The Pelagic cohort was supported by the French National Research Agency (ANR-2010-PRSP-007) and the French Research Institute for Public Health (AMC11004NSA-DGS).r PIAMAr The PIAMA study was supported by the Netherlands Organization for Health Research and Development; The Netherlands Organization for Scientific Research; The Netherlands Asthma Fund; The Netherlands Ministry of Spatial Planning, Housing, and the Environment; and The Netherlands Ministry of Health, Welfare, and Sport.r Piccolipiur The Piccolipiu project was financially supported by the Italian National Center for Disease Prevention and Control (CCM grants years 2010 and 2014) and by the Italian Ministry of Health (art 12 and 12 bis D.Igs 502/92).r PRIDE Studyr The PRIDE Study is supported by grants from the Netherlands Organization for Health Research and Development, the Radboud Institute for Health Sciences, and the Lung Foundation Netherlands.r Project Vivar National Institutes of Health (R01 HD034568, UGOD023286).; r RAINE Studyr The Western Australian Pregnancy Cohort (Raine Study) has been funded by program and project grants from the Australian National Health and Medical Research Council, the Commonwealth Scientific and Industrial Research Organization, Healthway, and the Lions Eye Institute in Western Australia. The University of Western Australia (UWA), Curtin University, the Raine Medical Research Foundation, the Telethon Kids Institute, the Women's and Infant's Research Foundation (KEMH), Murdoch University, The University of Notre Dame Australia, and Edith Cowan University provide funding for the Core Management of the Raine Study.r REPRO_PLr National Science Centre, Poland, under the grant DEC-2014/15/3/NZ7/00998, FP7 HEALS Grant No. 603946 and the Ministry of Science and Higher Education, under grant agreement no. 3068/7.PR./2014/2.r RHEAr The Rhea project was financially supported by European projects (EU FP6-2003-Food-3-NewGeneris, EU FP&.STREP Hiwate, EU FP7 ENV.2007.1222 Project No. 211250 Escape, EU FP7-2008-ENV-1.2.1.4 Envirogenomarkers, EU FP7-HEALTH-2009-single stage CHICOS, EU FP7 ENV.2008.1.2.1.6. Proposal No. 226285 ENIIIECO, EU-FP/-HEALTH-2012 Proposal No 308333 HELIX) and the Greer: Ministry of Health (Program of Prevention of obesity and ileuMdevelopmental disorders in preschool children, in Heraklion District, Crete, Greece: 2011-2014; Rhea Plus: Primary Prevention Program of Environmental Risk Factors for Reproductive Health, and Child Health 2012-15).r Slovak PCB studyr Support was provided by US National Institutes of Health grants R01 CA096525, R03 TW007152, P30 E5001247, and K12 ES019852.r STEPSr This study was supported by the University of Turku, Abo Akademi University, the Turku University Hospital, and the City of Turku, as well as by the Academy of Finland (grants 121569 and 123571), the Juno Vainio Foundation, the Yrjo Jahnsson Foundation, the TorKu.r SWSr The SWS is supported by grants from the Medical Research Council, National Institute for Health Research Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton National Health Service Foundation Trust, and the European Union's Seventh Framework Programme. (P7/2007-2013), project EarlyNutrifion (grant 289346). Study participants were drawn from a cohort study funded by the Medical Research council and the Dunhill Medical Trust.

The key activity in good practice of occupational medicine is to control, on a regular basis, the workers' health and how it is affected by the work environment and - consequently - to provide the employers and employees with advice regarding the organization, ergonomics, physiology and psychology of work. Occupational medicine practitioners should remember that certain duties are performed both at work and at home. This issue is particularly important in preventive healthcare of pregnant working women. Taking the above into consideration, we reviewed the literature with respect to nuisance and occupational risk factors, which might be associated with professional and household duties. The research indicates the need to reduce activities that require frequent bending or lifting, put a women at risk of falling or cause excess occupational stress for pregnant women. We would like to draw the doctors' attention to the possibility of exceeding a 4-hour limit of work at video display terminals and negative effects of low physical exercise and sitting for a long time both at work and at home. Since long working hours (over 40 h/week) affect the course of pregnancy negatively, total working time at work (including any additional jobs) and at home must be taken into account in the occupational risk assessment. To sum up, we emphasize that preventive healthcare of pregnant working women should mainly include education programmes. Women need to know how to perform their work safely and pay attention to the scope and frequency of household tasks (duties).Kluczowym działaniem w ramach dobrych praktyk w opiece profilaktycznej jest systematyczna kontrola stanu zdrowia pracujących, ocena jego związku przyczynowego z warunkami pracy oraz w efekcie – udzielanie pracownikom i pracodawcom porad w zakresie organizacji pracy, ergonomii, fizjologii i psychologii pracy. Lekarz medycyny pracy powinien przy tym pamiętać, że niektóre czynności wykonywane przez pracowników nie tylko wchodzą w zakres obowiązków zawodowych, ale są wykonywane przez nich również w domu. Taka świadomość jest szczególnie ważna w opiece profilaktycznej nad pracującą ciężarną. Biorąc powyższe pod uwagę, autorzy niniejszej publikacji dokonali przeglądu piśmiennictwa pod kątem uciążliwości i czynników szkodliwych, na które kobiety w ciąży mogą być narażone w trakcie wykonywania pracy zawodowej i w warunkach domowych. Przedstawione wyniki badań wskazują konieczność minimalizowania u ciężarnych czynności wymuszających częste pochylanie się, grożących upadkiem, wymagających dźwigania oraz związanych z nadmiernym stresem. Zwrócono uwagę na możliwość przekraczania łącznie w pracy i w domu obecnie obowiązującego w polskim prawie limitu 4 godzin pracy przy komputerze – głównie ze względu na wiążący się z tym niekorzystny wpływ niskiej aktywności fizycznej i długotrwale utrzymywanej pozycji siedzącej. Ze względu na niekorzystny wpływ pracy powyżej 40 godz. tygodniowo na przebieg ciąży w ocenie ryzyka zawodowego wskazana jest analiza łącznego czasu pracy ciężarnej z uwzględnieniem dodatkowych prac zarobkowych i zajęć domowych. W podsumowaniu autorzy podkreślają, że opieka profilaktyczna nad pracującą ciężarną wymaga edukowania ciężarnych w zakresie sposobu wykonywania obowiązków służbowych, ze zwróceniem uwagi na zakres i częstość czynności domowych analogicznych do zawodowych. Med. Pr. 2015;66(5):713–724.

BACKGROUND AND OBJECTIVE We hypothesized that maternal prenatal and children urine metabolite concentration of phthalates would be associated with food allergy and early eczema among inner-city children. The study was based on data from the Polish Mother and Child Cohort. METHODS Prenatal and postnatal exposure to the following phthalates: diethyl phthalate, diisobutyl phthalate, di-n-butyl phthalate, butyl-benzyl phthalate, di(2-ethylhexyl) phthalate, diisononyl phthalate, and di-n-octyl phthalate were determined by measuring phthalate metabolites in the urine collected from the mothers during the third trimester of pregnancy and from their children at age 2 years. Pre- and postnatal observations limited the response rate and final sample size; data from 147 participants were included in the analysis. Children's health status was assessed at 24 months of age by using a questionnaire administered to the mothers. We studied associations between the urine level of phthalates and the presence of food allergy and atopic dermatitis in logistic regression analysis. All associations were adjusted for independent risk factors of dependent variables. Associations with atopic dermatitis were adjusted for the effect of atopy in the family, the father's education, frequency of house cleaning, and breastfeeding; associations with food allergy were adjusted for the presence of pets at home during pregnancy and breastfeeding. RESULTS The prevalence of the outcomes were as follows: atopic dermatitis, 12.2%, and food allergy, 48.9%. We showed that higher urine concentrations of monobenzyl phthalate in mothers during pregnancy increased the risk of food allergy in children during the first 2 years of life (odds ratio 4.17 [95% confidence interval, 1.17-17.89]). There were no associations with children's urine and allergic symptoms. CONCLUSIONS Results of our study indicated awareness of environmental factors that may affect children's health because the phthalates were shown to be risk factors for food allergy in children.

Nowadays special attention is paid to prenatal exposures to maternal lifestyle factors and their impact on a child development.The objective of this study was to evaluate the impact of modifiable maternal lifestyle factors on child neurodevelopment based on the Polish Mother and Child Cohort study.The current analysis included 538 mother-child pairs. The following factors related to maternal lifestyle were considered: smoking and environmental tobacco smoke (ETS) exposure (based on the cotinine level in maternal saliva measured using LC-ESI+MS/MS method), alcohol consumption and leisure-time physical activity (LTPA) in pregnancy, pre-pregnancy BMI, and folic acid supplementations before and during pregnancy based on questionnaire data. Psychomotor development was assessed in children at the ages of one and two by the Bayley Scales of Infant and Toddler Development.Significant association was observed between prenatal exposure to tobacco constituents and a decreased child motor development in assessments performed at both ages (β=-0.8, p=0.01; β=-1.4, p0.001). Maternal pre-pregnancy underweight was associated with decreased language abilities at 12 months of age (β=-5.2, p=0.01) and cognitive and motor development at 24 months of age, for which the associations were of borderline significance (p=0.06). The recommended level of LTPA during pregnancy was beneficial for child language development at two years of age (β=4.8, p=0.02). For alcohol and folic acid consumption there were no significant associations with any of the analyzed domains of child neurodevelopment.Children prenatally exposed to tobacco compounds and those of underweight mothers had a decreased psychomotor development. The recommended level of LTPA during pregnancy had positive impact on child development. These results underscore the importance of policies and public health interventions promoting healthy lifestyle among women in reproductive age and during pregnancy.

BACKGROUND: Many recent studies indicate that prenatal maternal distress increases the risk of allergic diseases in children. The mechanisms that favor it are still unclear. OBJECTIVES: We aimed to assess the association between exposure to different kinds of prenatal stress and the occurrence of atopic dermatitis, food allergy, wheezing, and recurrent respiratory tract infections in children. METHODS: The study population consisted of 370 mother–child pairs from a Polish Mother and Child Cohort (REPRO_PL). The analysis was restricted to the women who worked at least one month during the pregnancy period. Maternal psychological stress during pregnancy was assessed based on the Subjective Work Characteristics Questionnaire, the Perceived Stress Scale, and the Social Readjustment Rating Scale. The presence of atopic dermatitis, food allergy, wheezing, and recurrent respiratory tract infections in children was evaluated by doctors at 12 months of age. RESULTS: In a univariate model, we showed significant association between maternal life stress (according to the Perceived Stress Scale) and stressful life events (according to the Social Readjustment Rating Scale) and infant wheezing (at least 1 episode of wheezing during the first year of life). A multivariate model of logistic regression analysis revealed that maternal stress during pregnancy, described by the Social Readjustment Rating Scale, increased the risk of wheezing in children (OR 1.09, 95% CI 1.01–1.02) independently from other predictors of wheezing previously determined in this cohort, such as the number of infections and maternal smoking. We observed also significant positive association between maternal life stress during pregnancy measured by the Perceived Stress Scale and the risk of recurrent respiratory tract infections in the first year of life, however it was not significant after adjustment for confounding variables. CONCLUSIONS: Maternal stress during pregnancy increases the risk of childhood wheezing. The effects of stress during pregnancy on the onset of allergic diseases in children should be developed and translated into early prevention strategies.

Studies on the impact of micronutrient levels during different pregnancy periods on child psychomotor functions are limited. The aim of this study was to evaluate the association between maternal plasma concentrations of selected micronutrients, such as: copper (Cu), zinc (Zn), selenium (Se), and child neuropsychological development. The study population consisted of 539 mother-child pairs from Polish Mother and Child Cohort (REPRO_PL). The micronutrient levels were measured in each trimester of pregnancy, at delivery and in the cord blood. Psychomotor development was assessed in children at the age of 1 and 2 years using the Bayley Scales of Infant and Toddler Development. The mean plasma Zn, Cu and Se concentrations in the 1st trimester of pregnancy were 0.91±0.27mg/l, 1.98±0.57mg/l and 48.35±10.54μg/l, respectively. There were no statistically significant associations between Cu levels and any of the analyzed domains of child development. A positive association was observed between Se level in the 1st trimester of pregnancy and child language and motor skills (β=0.18, p=0.03 and β=0.25, p=0.005, respectively) at one year of age. Motor score among one-year-old children decreased along with increasing Zn levels in the 1st trimester of pregnancy and in the cord blood (β=-12.07, p=0.003 and β=-6.51, p=0.03, respectively). A similar pattern was observed for the association between Zn level in the 1st trimester of pregnancy and language abilities at one year of age (β=-7.37, p=0.05). Prenatal Zn and Se status was associated with lower and higher child psychomotor abilities, respectively, within the first year of life. Further epidemiological and preclinical studies are necessary to confirm the associations between micronutrient levels and child development as well as to elucidate the underlying mechanisms of their effects.

The developing fetus is especially vulnerable to environmental toxicants, including tobacco constituents. The aim of this study was to assess the impact of environmental tobacco smoke (ETS) exposure during pregnancy on child neurodevelopment within the first two years of life. The study population consisted of 461 non-smoking pregnant women (saliva cotinine level

A global assessment of allergic diseases and prenatal and postnatal exposure to various environmental risk factors is needed to enable early prevention of allergic diseases. This study was designed to evaluate an inner-city urban birth cohort to identify early environmental factors associated with atopic dermatitis and food allergy, as well as the incidence of wheezing during the 1st year of life. We evaluated 501 children from the Polish Mother and Child Cohort Study (2007-2011). The children's health, socioeconomic status, and housing conditions were assessed using a questionnaire. Exposure to tobacco was assessed based on questionnaire data and cotinine measurements. Multiple regression analysis showed that parental atopy, higher paternal education, and more frequent house cleaning significantly predicted atopic dermatitis in the 1st year of life; odds ratio (OR) for the variables was 2.7 (95% CI, 1.3-1.57), 2.8 (95% CI, 1.5-5.0), and 1.8 (95% CI, 1.1-2.9), respectively. Keeping a pet at home during pregnancy increased the risk of food allergy (OR, 1.48; 95% CI, 1.02-2.16). Longer breast-feeding decreased the risk of both food allergy (OR, 0.88; 95% CI, 0.82-0.95) and atopic dermatitis (OR, 0.9; 95% CI, 0.8-0.95) in the 1st year of life. Positive association between maternal exposure to increased concentrations of particulate matter 10 and atopic dermatitis in univariate analyses was found. Atopic dermatitis/food allergy and wheezing/inhaled corticosteroid use had distinct risk factors. The risk factor profile of atopic dermatitis/food allergy in early childhood that is defined in this study support the following recommendations: (i) longer breast-feeding, (ii) avoid pets during gestation, (iii) avoid too frequent house cleaning, and (iv) living in an area with decreased traffic density. This study was a part of the clinical trial NCT01861548 registered in www.clinicaltrials.gov.

Background Widespread phthalate exposure has prompted investigations concerning their potential adverse health effects. Aim The objective of this study was to evaluate the impact of pre and early postnatal phthalate exposure on child psychomotor development based on the data from the prospective Polish Mother and Child Cohort Study (REPRO PL). Study design, subjects and outcome measures Phthalate exposure was determined by measuring 11 phthalate metabolites (MEP, MiBP, MnBP, 3OH-MnBP, MBzP, MEHP, 5OH-MEHP, 5oxo-MEHP, OH-MiNP, oxo-MiNP, and MnOP) in the urine collected from mothers during the third trimester of pregnancy (prenatal exposure) and from their children at the 24th month of age (postnatal exposure). The analysis was performed by the HPLC–MS/MS method. Psychomotor development was assessed in children at the age of 2 years by the Bayley Scales of Infant and Toddler Development. Results Child motor development was inversely associated with natural log concentrations (μg/g creatinine) of 3OH-MnBP (β = − 2.3; 95% CI − 4.0 to − 0.6), 5OH-MEHP (β = − 1.2; 95% CI − 2.2 to − 0.3), 5oxo-MEHP (β = − 1.8; 95% CI − 3.3 to − 0.2) and sum of DEHP metabolites (β = − 2.2; 95% CI − 3.6 to − 0.8), DnBP metabolites (β = − 1.9; 95% CI − 3.4 to − 0.4), and high molecular weight phthalates (β = − 2.5; 95% CI − 4.1 to − 0.9) in the urine collected from mothers during pregnancy after adjustment for a variety of potential confounders. Additional adjustment for postnatal phthalate exposure did not change the results. Postnatal child exposure to phthalates was not associated with any of the measured scores of child psychomotor development. Conclusions The study findings add further support to the possibility that prenatal phthalate exposure may be detrimental to child neurodevelopment and underscore the importance of policies and public health interventions aiming at reduction of such exposure.

The aim of this study was to characterize the PAH exposure level among the non-smoking Polish pregnant women and to identify the minimal set of PAH metabolites that specifically reflect environmental PAH exposure. The study population consisted of 210 non-smoking pregnant women. The urine sample was used for analysis of the following PAH metabolites: 1-, 2-, 3-, 4-, 9-hydroxyphenanthrene (1-, 2-, 3-, 4-, 9-OH-PHE), 1-hydroxypyrene (1-OH-PYR), 1,6 + 1,8-dihydroxypyrene (DI-OH-PYR), phenanthrene trans-1,2-dihydrodiol (PHE-1,2-diol) and phenanthrene trans-9,10-dihydrodiol (PHE-9,10-diol). The analysis of all the biomarkers was performed by gas chromatography–mass spectrometry after their derivatization. The mean PAH metabolite concentrations were in the range of 0.15 (± 0.2) μg/g creatinine for 9-OH-PHE to 5.9 (± 10.6) μg/g creatinine for PHE-9,10-diol. Women living in the city center had higher concentrations of 1-OH-PHE (β = 0.6; p = 0.04), 3-OH-PHE (β = 0.8; p = 0.02), 9-OH-PHE (β = 0.9; p = 0.02), and DI-OH-PYR (β = 1.0; p = 0.006) than those living outside the city center. The usage of coal for residential heating was a significant predictor of all PAH metabolites except for 9-OH-PHE (p = 0.1) and PHE-9,10-diol (p = 0.08). With the increasing cotinine levels we observed a significant increase in the concentrations of the following PAH metabolites: 3-OH-PHE (β = 0.2; p = 0.007), 4-OH-PHE (β = 0.3; p = 0.002), PHE-1,2-diol (β = 0.3; p

It has been hypothesized that the increase in allergic disorders may, in part, be a consequence of changing diet. The primary aim of this study was to assess the associations between occurrence of atopic dermatitis; food allergy; the incidence of wheeze inhaled glucocorticosteroid use in children during the 1st year of life; and cord blood concentrations of copper, zinc, vitamins (A and E), and glutathione peroxidase activity. We evaluated 240 1-year-old children from the Polish Mother and Child Cohort Study. Women were interviewed during pregnancy to collect demographic and socioeconomic data and medical and reproductive history. Exposure to tobacco constituents was assessed based on questionnaire data. At delivery, umbilical cord blood plasma was sampled. One year after the birth, the child's exposure and health status were examined. In the analyses a multivariable model was used. Higher zinc and copper concentrations in cord blood were associated with increased likelihood of wheezing in 1-year-old children. This effect was seen only among children exposed to tobacco smoke at home. We also showed significantly lower activity of glutathione peroxidase enzyme 3 in umbilical cord blood plasma of children with atopic dermatitis during the 1st year of life. There were no significant associations between vitamin A and E concentrations in plasma and children's health. We showed imbalance in the antioxidant defense system in cord blood, which may lead to development of atopic dermatitis or wheezing in infancy. The association between maternal nutrient status during pregnancy and child's health is complex and interacts with other environmental factors such as tobacco exposure. This study was a part of the clinical trial NCT01861548 registered at ClinicalTrials.gov.

Background: In Poland conditions related to or aggravated by the pregnancy, childbirth or the puerperium are one of the most common causes of sickness absence. The aim of the study was to analyze the occupational activity pattern during pregnancy and to evaluate the determinants of pregnancy-related temporary work disability confirmed by medical certificate. Materials and Methods: The presented analysis is based on data collected under the Polish Mother and Child Cohort Study. The study population consisted of 954 women who reported occupational activity during pregnancy. All women participating in the study were interviewed 3 times during pregnancy. Detail information on occupational activity during pregnancy and occupational stress, based on the Subjective Work Characteristics Questionnaire, was collected from all women. Results: The pregnant women had been issued medical certificate of temporary work disability because of conditions related to or aggravated by the pregnancy, childbirth or by the puerperium at 16 week of gestation on average and did not continue their activities until the end of pregnancy. The statistically significant determinants of receiving such medical certificate in the first trimester of pregnancy (≤ 12 weeks of pregnancy) comprised poor health condition and complications during pregnancy (OR = 1.4; p = 0.01), lower education (OR = 2.4; p < 0.001), socio-economic status (OR = 9.6; p = 0.03), use of public transport to commute to work (OR = 2.7; p < 0.001), a longer work commute (OR = 1.4; p = 0.008) and a higher level of occupational stress (OR = 3.0; p < 0.01). Waitresses, nurses and saleswomen received medical certificate of temporary work disability in the first trimester of pregnancy more frequently than office workers (OR = 4.2; p = 0.005; OR = 3.3; p = 0.02; OR = 2.3; p < 0.001 respectively). Conclusions: It is crucial to develop the model of cooperation between occupational medicine physicians and gynecologists and a greater involvement of the former in the prophylactic care of occupationally active pregnant women. It is also important to increase the employers' awareness of potential risks and arduousness at work to assure working conditions safe for the pregnancy outcome and health of both women and their babies. Med Pr 2014;65(1):65–72

A reliable assessment of smoking status has significant public health implications and is essential for research purposes. The aim of this study was to determine optimal saliva cotinine cut-off values for smoking during pregnancy. The analyses were based on data from 1771 women from the Polish Mother and Child Cohort. Saliva cotinine concentrations were assessed by high performance liquid chromatography coupled with tandem mass spectrometry (HPLC-ESI + MS/MS). The saliva cotinine cut-off value for active smoking was established at 10 ng/mL (sensitivity 96%, specificity 95%) and for passive smoking at 1.5 ng/mL (sensitivity 63%, specificity 71%). About 5% of the self-reported non-smoking women were classified as smokers based on the cotinine cut-off value. Significantly more younger, single, and less educated self-reported non-smokers had a cotinine concentration higher than 10 ng/mL compared to those who were older, married, and who had a university degree. Close to 30% of the non-smokers who indicated that smoking was not allowed in their home could be classified as exposed to passive smoking based on the cut-off value. The study suggests that self-reported smoking status is a valid measure of active smoking, whereas in the case of passive smoking, a combination of questionnaire data and biomarker verification may be required.

BACKGROUND During the past 25 years, many pregnancy and birth cohorts have been established. Each cohort provides unique opportunities for examining associations of early-life exposures with child development and health. However, to fully exploit the large amount of available resources and to facilitate cross-cohort collaboration, it is necessary to have accessible information on each cohort and its individual characteristics. The aim of this work was to provide an overview of European pregnancy and birth cohorts registered in a freely accessible database located at http://www.birthcohorts.net. METHODS European pregnancy and birth cohorts initiated in 1980 or later with at least 300 mother-child pairs enrolled during pregnancy or at birth, and with postnatal data, were eligible for inclusion. Eligible cohorts were invited to provide information on the data and biological samples collected, as well as the timing of data collection. RESULTS In total, 70 cohorts were identified. Of these, 56 fulfilled the inclusion criteria encompassing a total of more than 500,000 live-born European children. The cohorts represented 19 countries with the majority of cohorts located in Northern and Western Europe. Some cohorts were general with multiple aims, whilst others focused on specific health or exposure-related research questions. CONCLUSION This work demonstrates a great potential for cross-cohort collaboration addressing important aspects of child health. The web site, http://www.birthcohorts.net, proved to be a useful tool for accessing information on European pregnancy and birth cohorts and their characteristics.