Spanish Birth Cohort Research Articles

Modelling the potential clinical and economic impact of universal immunisation with nirsevimab versus standard of practice for protecting all neonates and infants in their first respiratory syncytial virus season in Spain

BackgroundRespiratory syncytial virus (RSV) is associated with substantial morbidity among infants. This study modelled the potential public health and economic impact of nirsevimab, a long-acting monoclonal antibody, as an immunoprophylactic strategy for all infants in Spain in their first RSV season.MethodsA static decision-analytic model of the Spanish birth cohort during its first RSV season was developed to estimate the impact of nirsevimab on RSV-related health events and costs versus the standard of practice (SoP). Spain-specific costs and epidemiological data were used as model inputs. Modelled outcomes included RSV-related outpatient visits, emerging room (ER) visits, hospitalisations – including pediatric intensive care unit (PICU) admission, mechanical ventilation, and inpatient mortality.ResultsUnder the current SoP, RSV caused 151,741 primary care visits, 38,798 ER visits, 12,889 hospitalisations, 1,412 PICU admissions, and 16 deaths over a single season, representing a cost of €71.8 million from a healthcare payer perspective. Universal immunisation of all infants with nirsevimab was expected to prevent 97,157 primary care visits (64.0% reduction), 24,789 ER visits (63.9%), 8,185 hospitalisations (63.5%), 869 PICU admissions (61.5%), and 9 inpatient deaths (52.6%), saving €47.8 million (62.4%) in healthcare costs.ConclusionsThese results suggest that immunisation with nirsevimab of all infants experiencing their first RSV season in Spain is likely to prevent thousands of RSV-related health events and save considerable costs versus the current SoP.

The impact of prenatal mercury on neurobehavioral functioning longitudinally assessed from a young age to pre-adolescence in a Spanish birth cohort

The objective is to investigate the relation between cord blood mercury concentrations and child neurobehavioural functioning assessed longitudinally during childhood until pre-adolescence. MethodsThe study involves mothers and their offspring engaged in the Spanish INMA birth cohort (n = 1147). Total mercury (THg) was determined in cord blood. Behavioural problems were assessed several times during childhood using the ADHD-DSM-IV at age 4, SDQ at ages 7 and 11, CPRS-R:S and the CBCL at ages 7, 9 and 11. Covariates were obtained through questionnaires during the whole period. Multivariate generalised negative binomial (MGNB) models or mixed-effects MGNB (for those tests with information at one or more time points, respectively) were used to investigate the relation between cord blood THg and the children's punctuations. Models were adjusted for prenatal fish intake. Effect modification by sex, prenatal and postnatal fish intake, prenatal fruit and vegetable intake, and maternal polychlorinated biphenyl concentrations (PCBs) was assessed by interaction terms. ResultsThe geometric mean ± standard deviation of cord blood THg was 8.22 ± 2.19 μg/L. Despite adjusting for fish consumption, our results did not show any statistically significant relationship between prenatal Hg and the children's performance on behavioural tests conducted between the ages of 4 and 11. Upon assessing the impact of various factors, we observed no statistically significant interaction. ConclusionDespite elevated prenatal THg exposure, no association was found with children's behavioural functioning assessed from early childhood to pre-adolescence. The nutrients in fish could offset the potential neurotoxic impact of Hg. Further birth cohort studies with longitudinal data are warranted.

Prenatal Exposure to Multiple Endocrine-Disrupting Chemicals and Childhood BMI Trajectories in the INMA Cohort Study.

Prenatal exposure to endocrine-disrupting chemicals (EDCs) may disrupt normal fetal and postnatal growth. Studies have mainly focused on individual aspects of growth at specific time points using single chemical exposure models. However, humans are exposed to multiple EDCs simultaneously, and growth is a dynamic process. The objective of this study was to evaluate the associations between prenatal exposure to EDCs and children's body mass index (BMI) growth trajectories using single exposure and mixture modeling approaches. Using data from the INfancia y Medio Ambiente (INMA) Spanish birth cohort (), prenatal exposure to persistent chemicals [hexachlorobenzene (HCB), 4-4'-dichlorodiphenyldichloroethylene (DDE), polychlorinated biphenyls (PCB-138, -150, and -180), 4 perfluoroalkyl substances (PFAS)] and nonpersistent chemicals (8 phthalate metabolites, 7 phenols) was assessed using blood and spot urine concentrations. BMI growth trajectories were calculated from birth to 9 years of age using latent class growth analysis. Multinomial regression was used to assess associations for single exposures, and Bayesian weighted quantile sum (BWQS) regression was used to evaluate the EDC mixture's association with child growth trajectories. In single exposure models exposure to HCB, DDE, PCBs, and perfluorononanoic acid (PFNA) were associated with increased risk of belonging to a trajectory of lower birth size followed by accelerated BMI gain by 19%-32%, compared with a trajectory of average birth size and subsequent slower BMI gain [e.g., relative risk ratio (RRR) per doubling in DDE (95% CI: 1.05, 1.35); RRR for (95% CI: 1.05, 1.66)]. HCB and DDE exposure were also associated with higher probability of belonging to a trajectory of higher birth size and accelerated BMI gain. Results from the BWQS regression showed the mixture was positively associated with increased odds of belonging to a BMI trajectory of lower birth size and accelerated BMI gain (odds ratio per 1-quantile increase of the ; credible interval: 1.03, 2.61), with HCB, DDE, and PCBs contributing the most. This study provides evidence that prenatal EDC exposure, particularly persistent EDCs, may lead to BMI trajectories in childhood characterized by accelerated BMI gain. Given that accelerated growth is linked to a higher disease risk in later life, continued research is important. https://doi.org/10.1289/EHP11103.

Influence of genetic polymorphisms on arsenic methylation efficiency during pregnancy: Evidence from a Spanish birth cohort

BackgroundInorganic arsenic (iAs) is a widespread toxic metalloid. It is well-known that iAs metabolism and its toxicity are mediated by polymorphisms in AS3MT and other genes. However, studies during pregnancy are scarce. We aimed to examine the role of genetic polymorphisms in AS3MT, GSTO2, N6AMT1, MTHFR, MTR, FTCD, CBS, and FOLH1 in iAs methylation efficiency during pregnancy. MethodsThe study included 541 pregnant participants from the INMA (Environment and Childhood) Spanish cohort. Using high-performance liquid chromatography coupled to inductively coupled plasma-tandem mass, we measured arsenic (iAs and the metabolites monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA)) in urine samples collected during the first trimester. iAs methylation efficiency was determined based on relative concentrations of the As metabolites in urine (%MMA, %DMA, and %iAs). Thirty-two single nucleotide polymorphisms (SNPs) in nine genes were determined in maternal DNA; AS3MT haplotypes were inferred. We assessed the association between genotypes/haplotypes and maternal As methylation efficiency using multivariate linear regression models. ResultsThe median %MMA and %DMA were 5.3 %, and 89 %, respectively. Ancestral alleles of AS3MT SNPs (rs3740393, rs3740390, rs11191453, and rs11191454) were significantly associated with higher %MMA, %iAs, and lower %DMA. Pregnant participants with zero copies of the GGCTTCAC AS3MT haplotype presented a higher %MMA. Statistically significant associations were also found for the FOLH1 SNP rs202676 (β 0.89 95%CI: 0.24, 1.55 for carriers of the G allele vs. the A allele). ConclusionsOur study shows that ancestral alleles in AS3MT polymorphisms were associated with lower As methylation efficiency in early pregnancy and suggests that FOLH1 also plays a role in As methylation efficiency. These results support the hypothesis that As metabolism is multigenic, being a key element for identifying susceptible populations.

Associations of residential greenspace exposure and fetal growth across four areas in Spain.

An accumulating body of evidence has associated exposure to greenspace with improved birth outcomes, including higher birth weight and lower risk of low birth weight; however, evidence on such association with in-utero fetal growth is scarce. We explored the influence of maternal exposure to residential greenspace and fetal growth in four INMA (Infancia y Medio Ambiente) Spanish birth cohorts (2003-2008), with 2,465 participants. Residential greenspace was characterised by the Normalised Difference Vegetation Index (NDVI) average across 100m, 300m, and 500m buffers around the residence. Repeated ultrasound measurements of the abdominal circumference (AC), biparietal diameter (BPD), femur length (FL), and estimated fetal weight (EFW) were used. We created customised-generalised least squares models to evaluate associations of residential greenspace exposure on each fetal growth parameter, controlled for the relevant confounders. There were associations between the 500m buffer and BPD, FL, and AC. We also found associations in the 300m buffer and FL and AC. The associations in the 100m buffer were null. Estimates were higher among participants with lower socioeconomic status. Mediation analyses found that air pollution might explain 15-37% of our associations. Mediation by physical activity was not observed. Greenspace exposure may be beneficial for fetal growth.

Prenatal and child vitamin D levels and allergy and asthma in childhood.

Early-life vitamin D deficiency may impair immune system development contributing to allergy and asthma onset. Findings from prospective studies are inconsistent. To examine whether maternal and child vitamin D levels are associated with allergic and asthma-related symptoms throughout childhood in a Spanish birth cohort. 25-Hydroxyvitamin D3 (25(OH)D3) levels were measured in the serum of pregnant women (N = 2525) and children (N = 803). Information on allergic and asthma-related symptoms was obtained from repeated questionnaires from 1 to 9 years. A total of 19% of mothers and 24% of children had deficient 25(OH)D3 levels (<20 ng/ml). Higher child 25(OH)D3 levels at 4 years were associated with lower odds of atopic eczema from 4 to 9 years (adjusted odds ratio = 0.90; 95% CI = 0.84-0.97 per 5 ng/ml). Higher maternal and child 25(OH)D3 levels were associated with a lower prevalence of late-onset wheezing at the limit of statistical significance (adjusted relative risk ratio (RRRadj) = 0.86; 95% CI = 0.74-1.00 and RRRadj = 0.76; 95% CI = 0.58-1.02 per 5 ng/ml, respectively). All the remaining associations were null. Child 25(OH)D3 levels at pre-school age are associated with a reduced odds of atopic eczema in later childhood and both maternal and child levels may reduce the prevalence of late-onset wheezing. In this Spanish birth cohort, with a total of 19% of mothers and 24% of children with deficient levels of vitamin D, higher child vitamin D at 4 years of age was associated with reduced odds of atopic eczema up to 9 years. There was also some evidence that higher maternal and child vitamin D levels reduced the prevalence of late-onset wheezing. Although these findings need replication, they may imply optimal vitamin D levels at pre-school age to prevent atopic eczema.

The association between maternal ultra-processed food consumption during pregnancy and child neuropsychological development: A population-based birth cohort study

Maternal ultra-processed food (UPF) consumption during pregnancy may adversely affect child development. Pregnancy sugar-sweetened beverage consumption (as a part of UPF) has been associated with child cognitive dysfunction in the general population, but the role of total UPF consumption during pregnancy in later child neuropsychological development has not been studied. We aimed to analyse the association between maternal pregnancy UPF consumption and child neurodevelopment. This study involved 2377 pairs of pregnant women and their offspring from a Spanish birth cohort (recruitment period: 2004-2008, INMA project). Dietary intake was estimated using a 101-item food frequency questionnaire in the third trimester of pregnancy. The NOVA classification was used to identify UPFs, and their consumption was calculated as the daily percentage of total food consumption and categorized into tertiles. Child neuropsychological development was assessed with the Bayley Scales of Infant and Toddler Development (1-year-old, n=1929) and the McCarthy Scales of Children's Abilities (4-5 years-old, n=1679). Potential associations were analysed using multivariate linear regression models adjusted for a range of family and child characteristics. UPF consumption among pregnant women represented an average of 17% of the total diet, with sugar-sweetened beverages being the most commonly consumed type of UPF (40%). Children born to mothers in the highest tertile of UPF consumption (28.9% or more of the total diet) vs the lowest tertile (7.2% or less), showed a lower score (B=-2.29 [95% Confidence Interval (CI),-4.13;-0.46]) in the Verbal Scale of the McCarthy Scales (p-for-trend=0.02). No associations were observed with the McCarthy Scales assessing other cognitive domains or with the Bayley Scales. Of the seven cognitive domains studied, we observed an adverse association between maternal consumption of UPF during pregnancy and verbal functioning in early childhood, which is an important cognitive domain of neurodevelopment.

Maternal occupational exposures and fetal growth in a Spanish birth cohort.

While the epidemiologic literature suggests certain maternal occupational exposures may be associated with reduced measures of size at birth, the occupational literature employing fetal biometry data to assess fetal growth is sparse. The present study examines associations between maternal occupational exposures and ultrasound-measured fetal growth. We included 1,739 singleton pregnancies from the INfancia y Medio Ambiente (INMA) project (2003-2008). At 32 weeks of pregnancy, interviewers ascertained mothers’ employment status and assessed job-related physical loads, work schedules, and job strain during pregnancy. Job titles were linked to a job-exposure matrix to estimate exposure to 10 endocrine disrupting chemical (EDC) groups. We calculated z-scores from longitudinal growth curves representing trajectories from 0-12, 12-20 and 20-34 gestational weeks for abdominal circumference (AC), biparietal diameter (BPD), femur length (FL), and estimated fetal weight (EFW). Linear mixed models clustered by IMNA region (i.e., Gipuzkoa, Sabadell, Valencia) were used to examine associations between occupational exposures and fetal growth. Effect estimates are presented as percentage change in fetal growth. There was limited evidence of associations between work-related non-chemical stressors and fetal growth. We observed associations of similar magnitude between multiple EDC groups and decreased EFW trajectories during 20-34 gestational weeks (phthalates: -1.4% [-3.5, 0.6%]; alkylphenolic compounds (APCs): -1.1% [-2.3, 0.1%]; miscellaneous chemicals: -1.5% [-3.7, 0.8%]), while miscellaneous chemicals were associated with increased BPD from 12-20 weeks (2.1% [0.8, 3.5%]). Notably, 67% of women exposed to phthalates were hairdressers; 68% of women exposed to APCs worked as domestic cleaners. In conclusion, we found limited evidence that maternal occupational exposures impact fetal growth. Further research should consider the combined impact of multiple workplace exposures.

Prenatal exposure to phthalates and phenols and preclinical vascular health during early adolescence.

Exposure to endocrine-disrupting chemicals may increase cardiovascular risk from early life, but studies in children have shown inconsistent results, most focused on analysis of single chemicals, and none included measures of micro-vascularization as early preclinical markers. This study aimed to evaluate the association between prenatal exposure to phthalates and phenols and macro- and microvascular health during early adolescence. Using data from a Spanish birth cohort (n=416), prenatal exposure to eight phthalate metabolites and seven phenols (bisphenol A, four parabens, benzophenone-3, triclosan) were assessed using first and/or third trimester spot-urine concentrations. Macrovascular health (systolic and diastolic blood pressure (SBP and DBP, mmHg), pulse wave velocity (PWV, m/s)) and microvascular health (central retinal artery/vein equivalent (CRAE/CRVE, μm)), were measured at 11 years old. Linear regression models assessed associations for individual chemicals and Bayesian weighted quantile sum regression (BWQS) evaluated the overall association of the phthalate and phenol mixture with cardiovascular health. In single exposure models, bisphenol-A was associated with decreased PWV (β per doubling of exposure=-0.06; 95% CI: -0.10, -0.01). Mono-iso-butyl phthalate was associated with an increase in CRAE (β=1.89; 95% CI: 0.34, 3.44). Methyl- and butyl-parabens were associated with a decrease in CRVE (β=-0.71; 95% CI: -1.41, -0.01) and (β=-0.96; 95% CI: -1.57, -0.35), respectively. No statistically significant associations were observed between any of the exposures and SBP or DBP. BWQS models showed no evidence of associations between the phthalate and phenol mixture and any of the outcomes. Our results provide little evidence to suggest that prenatal exposure to phthalates and phenols is associated with macro- or microvascular health during early adolescence, except a few associations with certain compounds. Errors in exposure measurement and reduced variability in cardiovascular measures at this early age limit our ability to draw strong conclusions.

Identifying Sensitive Windows of Exposure to NO2 and Fetal Growth Trajectories in a Spanish Birth Cohort.

Background:We previously identified associations between trimester-specific NO2 exposures and reduced fetal growth in the Spanish INfancia y Medio Ambiente (INMA) project. Here, we use temporally refined exposure estimates to explore the impact of narrow (weekly) windows of exposure on fetal growth.Methods:We included 1,685 women from INMA with serial ultrasounds at 12, 20, and 34 gestational weeks. We measured biparietal diameter (BPD), femur length, and abdominal circumference (AC) and from them calculated estimated fetal weight (EFW). We calculated z-scores describing trajectories of each parameter during early (0–12 weeks), mid (12–20 weeks), and late (20–34 weeks) pregnancy, based on longitudinal growth curves from mixed-effects models. We estimated weekly NO2 exposures at each woman’s residence using land-use regression models. We applied distributed lag nonlinear models to identify sensitive windows of exposure. We present effect estimates as the percentage change in fetal growth per 10 μg/m3 increase in NO2 exposure, and we calculated cumulative effect estimates by aggregating estimates across adjacent lags.Results:We identified weeks 5–12 as a sensitive window for NO2 exposure on late EFW (cumulative β = −3.0%; 95% CI = −4.1%, −1.9%). We identified weeks 6–19 as a sensitive window for late growth in BPD (cumulative β = −2.0%; 95% CI = −2.7%, −1.4%) and weeks 8–13 for AC (cumulative β = −0.68%; 95% CI = −0.97%, −0.40%). We found suggestive evidence that third trimester NO2 exposure is associated with increased AC, BPD, and EFW growth in late pregnancy.Conclusions:Our findings are consistent with the hypothesis that NO2 exposure is associated with alterations in growth of EFW, BPD, and AC dependent on the specific timing of exposure during gestation.

Prenatal arsenic exposure, arsenic methylation efficiency, and neuropsychological development among preschool children in a Spanish birth cohort

BackgroundPrenatal arsenic (As) exposure could negatively affect child neuropsychological development, but the current evidence is inconclusive. ObjectivesTo explore the relationship between prenatal urinary total As (TAs) concentrations, the As species and the methylation efficiency, and child neuropsychological development in a Spanish birth cohort. We also studied the effect modification produced by sex and several nutrients and elements. Materials and methodsStudy subjects were 807 mother–child pairs participating in the INMA (Childhood and Environment) Project. Urinary TAs and its metabolites, monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), inorganic As (iAs) and arsenobetaine were measured in the first trimester of pregnancy. Methylation efficiency was determined through the percentages of the metabolites and using principal component analysis. Children's neuropsychological development was assessed at the age of 4–5 years using the McCarthy Scales of Children's Abilities (MSCA). Multivariable linear regression models were built to assess the association between TAs, the As species and the maternal methylation efficiency, and the neuropsychological scores. We explored effect modification by sex, iron status, maternal nutrients status (serum manganese and selenium, and urinary zinc), and maternal vitamins intake (folate, and vitamins B12 and B6). ResultsThe geometric mean (95%CI) of ∑As (sum of DMA, MMA and iAs) was 7.78 (7.41, 8.17) μg/g creatinine. MMA concentrations were inversely associated with the scores for the general, verbal, quantitative, memory, executive function and working memory scales (i.e. β [CI95%] = −1.37 [-2.33, −0.41] for the general scale). An inverse association between %MMA and the memory scores was found. Children whose mothers had lower manganese, zinc and ferritin concentrations obtained lower scores on several MSCA scales with decreasing As methylation efficiency. DiscussionAn inverse association was observed between MMA concentrations and children's neuropsychological development. Maternal levels of manganese, zinc and ferritin affected the association between As methylation efficiency and MSCA scores.

Prenatal exposure to phthalates and phenols and pre-clinical cardiovascular health during early adolescence

BACKGROUND AND AIM: Exposure to endocrine-disrupting chemicals may increase cardiovascular risk from early life, but studies in children have shown inconsistent results, most focused on analysis of single chemicals, and none included measures of micro-vascularization as early pre-clinical markers. This study aimed to evaluate the association between prenatal exposure to phthalates and phenols and macro- and microvascular health during early adolescence. METHODS: Using data from a Spanish birth cohort (n=416), prenatal exposure to phthalate metabolites and phenols (bisphenol A, parabens, benzophenone-3, triclosan) was assessed using first and third trimester spot-urine concentrations. Macrovascular health (systolic and diastolic blood pressure (SBP and DBP, mmHg), pulse wave velocity (PWV, m/s)) and microvascular health (central retinal artery/vein equivalent (CRAE/CRVE, μm)), were measured at 11 years old. Linear regression models assessed associations for individual chemicals and Bayesian weighted quantile sum regression (BWQS) evaluated the overall association of each chemical group with cardiovascular health. RESULTS:In individual exposure models, BPA was associated with decreased PWV (β per doubling of exposure = –0.06; 95% CI: –0.10, -0.01). One phthalate, MiBP was associated with an increase in CRAE (β = 1.89; 95% CI: 0.34, 3.44). Two parabens, MEPA and BUPA were associated with a decrease in CRVE (β = -0.71; 95% CI: -1.41, -0.01) and (β = -0.96; 95% CI: -1.57, -0.35), respectively. No significant associations were observed between any of the exposures and SBP or DBP. In models using BWQS there was no evidence of associations between the phthalates or phenols mixture and any of the outcomes. CONCLUSIONS:Our results provide little evidence to suggest that prenatal exposure to phthalates and phenols is associated with macro or microvascular health during early adolescence, except a few associations with certain compounds. Errors in exposure measurement and reduced variability in cardiovascular measures at this early age limit our ability to draw strong conclusions. KEYWORDS: Phenols, phthalates, cardiovascular diseases, chemical exposures, Endocrine disrupting chemicals, mixtures analysis

Early-childhood BMI trajectories in relation to preclinical cardiovascular measurements in adolescence.

Cardiovascular diseases are the leading causes of morbidity and mortality. Overweight, obesity, and accelerated growth during early childhood have been associated with adverse cardiovascular outcomes in later life. Few studies have assessed whether trajectories of accelerated growth in early childhood are associated with preclinical cardiovascular measurements. We aimed to evaluate the associations between childhood body mass index (BMI) growth trajectories and measures of macro- and microvascular function in early adolescence. Measurements of macrovascular function (systolic and diastolic blood pressure (SBP and DBP), pulse wave velocity (PWV), and microvascular function (central retinal arteriolar/veinular equivalent) were assessed at 11 years old in a Spanish birth cohort study (n = 489). BMI trajectories from birth to 9 years were identified using latent class growth analysis. Multiple linear regression assessed the associations between the BMI trajectories and macro- and microvascular function. Compared to children with average birth size and slower BMI gain (reference), children with a lower birth size and accelerated BMI gain had increased SBP [β = 6.57; (95% CI 4.00, 9.15)], DBP [β = 3.65; (95% CI 1.45, 5.86)], and PWV [β = 0.14; (95% CI 0.01, 0.27)]. Children with higher birth size and accelerated BMI gain had increased SBP [β = 4.75; (95% CI 1.79, 7.71) compared to the reference. No significant associations between BMI trajectories and the microvascular measurements were observed. In conclusion, we found that childhood BMI trajectories characterized by accelerated growth are associated with preclinical macrovascular measurements in young adolescents.

Is Maternal Use of Paracetamol during Pregnancy Associated with Anogenital Distance in Male Newborns? The Results from the NELA Birth Cohort.

Paracetamol is the one of the most commonly used medications during pregnancy. However, its potential antiandrogenic effect has been suggested. The objective of this study was to evaluate associations between maternal paracetamol use during pregnancy and anogenital distance (AGD) in male newborns from a Spanish birth cohort. The study included two hundred and seventy-seven mother-male child pairs with self-reported paracetamol use and frequency during each trimester of pregnancy. AGD measurements were taken employing standardized methods. The associations between maternal paracetamol use and AGD measures were evaluated using linear regression models, adjusting for potential confounders and covariates. Overall, 61.7% of pregnant women consumed paracetamol at any time of pregnancy with an average of 9.43 (SD = 15.33) days throughout pregnancy. No associations between the maternal use of paracetamol or its frequency and AGD measures among different trimesters or during the whole pregnancy were found in the adjusted final models. A non-differential misclassification error may have occurred—the recall of paracetamol intake independent of AGD measurements—introducing bias towards the null hypothesis. Nevertheless, the current evidence suggests that paracetamol might have a potential antiandrogenic effect especially in the early stages of fetal development. Thus, it would be highly recommendable to pursue further studies to elucidate the potential effects of paracetamol in human perinatal health and its use among pregnant women.

Maternal sleep duration and neonate birth weight: Apopulation-based cohort study.

To investigate the association between maternal sleep duration (an important health indicator) and neonate birth weight. The study included 2536 mother-neonate pairs of a Spanish birth cohort (2004-2006, INMA project). The exposures were questionnaire-based measures of sleep duration before and during pregnancy. The primary outcome was neonate birth weight score (g) standardized to 40weeks of gestation. In women sleeping for <7h/day before pregnancy, each additional hour of sleep increased birth weight score by 44.7g (P=0.049) in the minimally adjusted model, although findings were not statistically significant after considering other potential confounders (P>0.05). However, increasing sleep duration for the group of mothers who slept for more than 9h/day decreased birth weight score by 39.2g per additional hour (P=0.001). Findings were similar after adjusting for several sociodemographic confounders and maternal depression-anxiety clinical history as an intermediate factor. Similar but attenuated associations were observed with sleep duration in the second trimester of pregnancy. The relationship between maternal sleep duration before and during pregnancy and neonate birth weight is an inverse U-shaped curve. Excessive sleep duration may adversely affect neonate health through its impact on birth weight.

Residential Surrounding Greenspace and Mental Health in Three Spanish Areas.

Exposure to greenspace has been related to improved mental health, but the available evidence is limited and findings are heterogeneous across different areas. We aimed to evaluate the associations between residential exposure to greenspace and specific psychopathological and psychosomatic symptoms related to mental health among mothers from a Spanish birth cohort. Our study was based on data from 1171 women participating in two follow-ups of a population-based cohort in Valencia, Sabadell, and Gipuzkoa (2004–2012). For each participant, residential surrounding greenspace was estimated as the average of the satellite-based Normalized Difference Vegetation Index (NDVI) across different buffers around the residential address at the time of delivery and at the 4-year follow-up. The Symptom Checklist 90 Revised (SCL-90-R) was applied to characterize mental health at the 4-year follow-up. We developed mixed-effects logistic regression models controlled for relevant covariates to evaluate the associations. Higher residential surrounding greenspace was associated with a lower risk of somatization and anxiety symptoms. For General Severity Index (GSI), obsessive–compulsive, interpersonal sensitivity, depression, hostility, phobic anxiety, paranoid ideation, and psychoticism symptoms, we generally observed protective associations, but none attained statistical significance. Findings from this study suggested a potential positive impactof greenspace on mental health.

Risk and Protective Factors for Bullying at 11 Years of Age in a Spanish Birth Cohort Study.

(1) Background: Bullying affects a large number of children worldwide. This study has two objectives, to provide data on the prevalence of bullying in Spain, and to identify risk and protective factors associated with bullying. (2) Methods: Participants were 858 eleven-year-old children. Bullying was assessed using a short version of the Olweus Bully Victim Questionnaire, and the following data were gathered to explore potential predictors: individual (inattention, behavior problems, attention deficit hyperactivity disorder symptomatology, traumatic life events), family-related (sociodemographic characteristics, family context, child-parent relations), school-related (school characteristics, peer and social support, school environment) and community-related data. (3) Results: 9.3% of the children were victims, 1.4% bullies and 1.6% bully-victims. Results showed that a higher level of attention deficit hyperactivity disorder symptomatology increased the risk of victimization, whereas having better relationships with parents and stronger social support were associated with a lower risk of victimization. Children having strong peer relationships and social support was also associated with less risk of perpetrating bullying. Finally, having behavior problems at 8 years of age was associated with being a bully-victim. (4) Conclusions: The findings emphasize the importance of studying all bullying predictors together, regarding three of the roles children may take in bullying situations.

Prenatal exposure to perfluoroalkyl substances, immune-related outcomes, and lung function in children from a Spanish birth cohort study.

Prenatal exposure to perfluoroalkyl substances (PFASs) has been associated with impaired immune and respiratory health during childhood but the evidence is inconsistent and limited for lung function. We studied the association between prenatal PFASs exposure and immune and respiratory health, including lung function, up to age 7 years in the Spanish INMA birth cohort study. We assessed four PFASs in maternal plasma samples collected during the 1st trimester of pregnancy (years: 2003-2008): perfluorohexane sulfonate (PFHxS), perfluorooctane sulfonate (PFOS), perfluorooctanoate (PFOA), and perfluorononanoate (PFNA). Mothers reported the occurrence (yes/no) of lower respiratory tract infections, wheezing, asthma, and eczema in the previous 12 months at 1.5 and 4 years of the child (n = 1188) and at 7 years (n = 1071). At ages 4 (n = 503) and 7 (n = 992) years lung function was assessed using spirometry tests. The most abundant PFASs were PFOS and PFOA (geometric means: 5.80 and 2.31 ng/mL, respectively). The relative risk of asthma during childhood per each doubling in PFNA concentration was 0.74 (95 CI%: 0.57, 0.96). The relative risk of eczema during childhood per every doubling in PFOS concentration was 0.86 (95 CI%: 0.75, 0.98). Higher PFOA concentrations were associated with lower forced vital capacity and lower forced expiratory volume in 1 s z-scores at 4 years [β (95 CI %): -0.17 (-0.34, -0.01) and -0.13 (-0.29, 0.03), respectively], but not at 7 years. This longitudinal study suggests that different PFASs may affect the developing immune and respiratory systems differently. Prenatal exposure to PFNA and PFOS may be associated with reduced risk of respiratory and immune outcomes, particularly asthma and eczema whereas exposure to PFOA may be associated with reduced lung function in young children. These mixed results need to be replicated in follow-up studies at later ages.

Prediction of maternal and foetal exposures to perfluoroalkyl compounds in a Spanish birth cohort using toxicokinetic modelling

Prenatal exposures to perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) have been associated with child health outcomes, but many of these associations remain poorly characterized. The aim of this work was to provide new indicators of foetal exposure for the Spanish INMA birth cohort. First, a pregnancy and lactation physiologically based pharmacokinetic (PBPK) model was calibrated in a population framework to provide quantitative estimates for the PFOA and PFOS placental transfers in humans. The estimated distributions indicated that PFOA crosses the placental barrier at a rate three times higher than PFOS and shows a higher variability between mothers. The PBPK model was then used to back-calculate the time-varying daily intakes of the INMA mothers corrected for their individual history from a spot maternal concentration. We showed the importance of accounting for the mothers' history as different dietary intakes can result in similar measured concentrations at one time point. Finally, the foetal exposure was simulated in target organs over pregnancy using the PBPK model and the estimated maternal intakes. We showed that the pattern of PFOA and PFOS exposures varies greatly among the foetuses. About a third has levels of either one compound always higher than the levels of the other compound. The other two thirds showed different ranking of PFOA and PFOS in terms of concentrations in the target organs. Our simulated foetal exposures bring additional information to the measured maternal spot concentrations and can help to better characterize the prenatal exposure in target organs during windows of susceptibility.

Preventing Criminal Minds: Early Education Access and Adult Offending Behavior

In this paper we estimate the impact of a nationwide public preschool expansion that took place in Spain over the 1990s on criminal behavior later in time. We exploit variation in enrollment rates across Spanish regions and birth-cohorts, and we link education data to a unique administrative crime dataset recording offenses committed in the region of Catalonia over the period 2009-2014. We find that for the average birth cohort, Catalan municipality and year, a 1 percentage point increase in preschool exposure at age 3 yields 1.6% fewer crime actions during youth and young adulthood. We are able to account for region of origin, birth cohort, time and local fixed effects, as well as several region and time-specific controls. Leveraging detailed information on types of crime committed, we propose a categorization of offenses into those likely to have been rationally planned and driven by economic motives, and those in which emotional factors and lack of self-control play a significant role. On average, we find the benefits of preschool to be larger and more robust on crimes belonging to the latter category, suggesting that non-cognitive skills play an important role in explaining the overall effect.