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Background/objectivesA higher adherence to a Mediterranean diet has been shown to be protective against obesity in adults, but the evidence is still inconclusive in children at early ages. Our objective was to explore the association between adherence to Mediterranean Diet at the age of 4 and the prevalence of overweight, obesity, and abdominal obesity at 4 years of age, and incidence at the age of 8.Subjects/methodsWe analyzed data from children of the INMA cohort study who attended follow-up visits at age 4 and 8 years (n = 1801 and n = 1527, respectively). Diet was assessed at the age of 4 using a validated food frequency questionnaire. The adherence to MD was evaluated by the relative Mediterranean diet (rMED) score, and categorized as low (0–6), medium (7–10), and high (11–16). Overweight and obesity were defined according to the age-sex specific BMI cutoffs proposed by the International Obesity Task Force, and abdominal obesity as waist circumference >90th percentile. We used Poisson regression models to estimate prevalence ratios at 4 years of age, and Cox regression analysis to estimate hazard ratios (HR) from 4–8 years of age.ResultsIn cross-sectional analyses at the age of 4 no association was observed between adherence to MD and overweight, obesity, or abdominal obesity. In longitudinal analyses, a high adherence to MD at age 4 was associated with lower incidence of overweight (HR = 0.38; 95% CI: 0.21–0.67; p = 0.001), obesity (HR = 0.16; 95% CI: 0.05–0.53; p = 0.002), and abdominal obesity (HR = 0.30; 95% CI: 0.12–0.73; p = 0.008) at the age of 8.ConclusionThis study shows that a high adherence to MD at the age of 4 is associated with a lower risk of developing overweight, obesity, and abdominal obesity at age 8. If these results are confirmed by other studies, MD may be recommended to reduce the incidence of obesity at early ages.

The potential etiological role of early acetaminophen exposure on Autism Spectrum Conditions (ASC) and Attention-Deficit/Hyperactivity Disorder (ADHD) is inconclusive. We aimed to study this association in a collaborative study of six European population-based birth/child cohorts. A total of 73,881 mother–child pairs were included in the study. Prenatal and postnatal (up to 18 months) acetaminophen exposure was assessed through maternal questionnaires or interviews. ASC and ADHD symptoms were assessed at 4–12 years of age using validated instruments. Children were classified as having borderline/clinical symptoms using recommended cutoffs for each instrument. Hospital diagnoses were also available in one cohort. Analyses were adjusted for child and maternal characteristics along with indications for acetaminophen use. Adjusted cohortspecific effect estimates were combined using random-effects meta-analysis. The proportion of children having borderline/clinical symptoms ranged between 0.9 and 12.9% for ASC and between 1.2 and 12.2% for ADHD. Results indicated that children prenatally exposed to acetaminophen were 19% and 21% more likely to subsequently have borderline or clinical ASC (OR = 1.19, 95% CI 1.07–1.33) and ADHD symptoms (OR = 1.21, 95% CI 1.07–1.36) compared to non-exposed children. Boys and girls showed higher odds for ASC and ADHD symptoms after prenatal exposure, though these associations were slightly stronger among boys. Postnatal exposure to acetaminophen was not associated with ASC or ADHD symptoms. These results replicate previous work and support providing clear information to pregnant women and their partners about potential long-term risks of acetaminophen use.

Mitochondria are sensitive to environmental toxicants due to their lack of repair capacity. Changes in mitochondrial DNA (mtDNA) content may represent a biologically relevant intermediate outcome in mechanisms linking air pollution and fetal growth restriction. We investigated whether placental mtDNA content is a possible mediator of the association between prenatal nitrogen dioxide (NO2) exposure and birth weight. We used data from two independent European cohorts: INMA (n = 376; Spain) and ENVIRONAGE (n = 550; Belgium). Relative placental mtDNA content was determined as the ratio of two mitochondrial genes (MT-ND1 and MTF3212/R3319) to two control genes (RPLP0 and ACTB). Effect estimates for individual cohorts and the pooled data set were calculated using multiple linear regression and mixed models. We also performed a mediation analysis. Pooled estimates indicated that a 10-μg/m3 increment in average NO2 exposure during pregnancy was associated with a 4.9% decrease in placental mtDNA content (95% CI: -9.3, -0.3%) and a 48-g decrease (95% CI: -87, -9 g) in birth weight. However, the association with birth weight was significant for INMA (-66 g; 95% CI: -111, -23 g) but not for ENVIRONAGE (-20 g; 95% CI: -101, 62 g). Placental mtDNA content was associated with significantly higher mean birth weight (pooled analysis, interquartile range increase: 140 g; 95% CI: 43, 237 g). Mediation analysis estimates, which were derived for the INMA cohort only, suggested that 10% (95% CI: 6.6, 13.0 g) of the association between prenatal NO2 and birth weight was mediated by changes in placental mtDNA content. Our results suggest that mtDNA content can be one of the potential mediators of the association between prenatal air pollution exposure and birth weight. Clemente DB, Casas M, Vilahur N, Begiristain H, Bustamante M, Carsin AE, Fernández MF, Fierens F, Gyselaers W, Iñiguez C, Janssen BG, Lefebvre W, Llop S, Olea N, Pedersen M, Pieters N, Santa Marina L, Souto A, Tardón A, Vanpoucke C, Vrijheid M, Sunyer J, Nawrot TS. 2016. Prenatal ambient air pollution, placental mitochondrial DNA content, and birth weight in the INMA (Spain) and ENVIRONAGE (Belgium) birth cohorts. Environ Health Perspect 124:659-665; http://dx.doi.org/10.1289/ehp.1408981.

Prenatal and early-life periods may be critical windows for harmful effects of air pollution on infant health. We studied the association of air pollution exposure during pregnancy and the first year of life with respiratory illnesses, ear infections, and eczema during the first 12-18 months of age in a Spanish birth cohort of 2,199 infants. We obtained parentally reported information on doctor-diagnosed lower respiratory tract infections (LRTI) and parental reports of wheezing, eczema, and ear infections. We estimated individual exposures to nitrogen dioxide (NO(2)) and benzene with temporally adjusted land use regression models. We used log-binomial regression models and a combined random-effects meta-analysis to estimate the effects of air pollution exposure on health outcomes across the four study locations. A 10-µg/m(3) increase in average NO(2) during pregnancy was associated with LRTI [relative risk (RR) = 1.05; 95% CI: 0.98, 1.12] and ear infections (RR = 1.18; 95% CI: 0.98, 1.41). The RRs for an interquartile range (IQR) increase in NO(2) were 1.08 (95% CI: 0.97, 1.21) for LRTI and 1.31 (95% CI: 0.97, 1.76) for ear infections. Compared with NO(2), the association for an IQR increase in average benzene exposure was similar for LRTI (RR = 1.06; 95% CI: 0.94, 1.19) and slightly lower for ear infections (RR = 1.17; 95% CI: 0.93, 1.46). Associations were slightly stronger among infants whose mothers spent more time at home during pregnancy. Air pollution exposure during the first year was highly correlated with prenatal exposure, so we were unable to discern the relative importance of each exposure period. Our findings support the hypothesis that early-life exposure to ambient air pollution may increase the risk of upper and lower respiratory tract infections in infants.

BACKGROUND:Vitamin D status during prenatal brain development may influence risk of attention deficit and hyperactivity disorder (ADHD) symptoms in childhood. However, there are no prospective studies addressing this hypothesis. We aimed to examine whether maternal vitamin D status in pregnancy is associated with risk of ADHD-like symptoms in offspring. METHODS:We conducted a prospective study analyzing data from 1,650 mother–child pairs from five birth cohorts embedded in the INMA Project (Spain, 1997–2008). Maternal vitamin D status in pregnancy was estimated by measuring plasma concentration of 25-hydroxyvitamin D3 [25(OH)D3] at 13 weeks of gestation. Children were assessed by teachers for ADHD-like symptoms at ages 4–5 years using the Diagnostic and Statistical Manual of Mental Disorders ADHD form list. RESULTS:After adjustment, the number of total ADHD-like symptoms in children decreased by 11% per 10 ng/ml increment of maternal 25(OH)D3 concentration (incidence rate ratio [IRR] = 0.89; 95% confidence interval [CI] = 0.80, 0.98). Similarly, the number of symptoms in the ADHD subscales decreased in relation to higher maternal 25(OH)D3 concentration (IRR per 10 ng/ml increment = 0.89; 95% CI = 0.79, 0.99 for the inattention scale; and IRR = 0.88; 95% CI = 0.78, 0.99 for the hyperactivity–impulsivity scale). Using diagnostic criteria, we found an association of increasing maternal 25(OH)D3 with a lower risk of ADHD DSM-IV (relative risk ratio per 10 ng/ml increment = 0.87; 95% CI = 0.72, 1.06) and ICD-10 hyperkinetic disorder (relative risk ratio = 0.72; 95% CI = 0.49, 1.04) in children. CONCLUSION:Higher maternal circulating levels of 25(OH)D3 in pregnancy are associated with lower risk of developing ADHD-like symptoms in childhood.

Background Vitamin D is traditionally associated with the metabolism of calcium and phosphorus, a process essential for the mineralization of hard tissue such as bone or tooth. Deficiency of this vitamin is a problem worldwide, however. Given the possibly significant role of Vitamin D in odontogenesis in children, the objective of our study was to determine the influence of vitamin D levels in the blood on dental anomalies in children between 6 and 10 years of age, by means of 25-hydroxy vitamin D tests performed during pregnancy and the first years of life. Methods The data analyzed were sourced from data belonging to the INMA-Asturias birth cohort, a prospective cohort study initiated in 2004 as part of the INMA Project. The 25-hydroxy vitamin D (25(OH)D) test was performed with samples from 188 children in the INMA-Asturias birth cohort with a dental examination performed between 6 and 10 years of age. The samples were taken at three stages: in the mother at 12 weeks of gestation, and subsequently in the child at 4 and 8 years of age. Diet, nutritional and oro-dental hygiene habits were also analyzed by means of questionnaires. Results The results indicate a significant association between caries and correct or incorrect brushing technique. With incorrect brushing technique, the prevalence of caries was 48.89%, but this dropped to 22.38% with correct brushing technique. An association was also found between tooth decay and frequency of sugar intake. The prevalence of caries was 24.54% with occasional sugar intake, but this rose to 56% with regular sugar intake. On the other hand, levels < 20 ng/ml in both mother and child at 8 years of age would also be risk factors (OR gest  = 2.51(1.01–6.36) and OR 8years  = 3.45(1.14–11.01)) for the presence of caries in children. The risk of caries practically tripled where 25(OH) D values were < 20 ng/ml. Conclusions Although incorrect brushing technique and regular sugar consumption was found to be the main cause of caries in the children, the low concentrations of vitamin D in the blood of the pregnant mothers may have magnified this correlation, indicating that the monitoring of vitamin D levels during pregnancy should be included in antenatal programmes. It is particularly striking that 50% of the children were deficient in vitamin D at the age of 4, and that dental floss was practically absent from regular cleaning routines.

This study aimed to investigate whether there are subgroups of children with different clusters of cardiovascular disease (CVD) risk factors at 4 and 8 years of age, and their patterns of change between these two time points. The analysis was conducted in 332 children who participated in the INMA-Asturias cohort (Spain) at 4 and at 8 years of age. The CVD risk factors were central obesity, dyslipidaemia, hyperglycaemia, and hypertension. Latent transition analysis was used to identify the different clusters and their probabilities of change. At 4 years, three subgroups were identified: no disorders (prevalence of 55.9%); some disorders (21.2%), and central obesity (22.9%). Three distinct subgroups were identified at 8 years: no disorders (59.8%); hypertension (17.9%), and central obesity (22.3%). Central obesity at 4 years tends to appear simultaneously with dyslipidaemia, while at 8 years it tends to appear simultaneously with dyslipidaemia and/or hypertension. Children aged 4 years with no disorders had a 93.7% probability of remaining in the same status at 8 years of age. Children aged 4 who had some disorders had a 67.7% of probability of having only hypertension and a 32.3% of probability of having central obesity. Children aged 4 in the central obesity subgroup had a 32.4% of probability of having no disorders at 8 years of age, while 67.6% still had central obesity. These exploratory findings suggest that children who do not present any disorder at 4 years of age tend to remain in that state at 8 years of age. And also that central obesity may play a major role in the development of other disorders, as the number of disorders with which it concomitantly occurs increases between the ages of 4 and 8 years.

An association between low socioeconomic status (SES) and lung cancer has been observed in several studies, but often without adequate control for smoking behavior. We studied the association between lung cancer and occupationally derived SES, using data from the international pooled SYNERGY study. Twelve case-control studies from Europe and Canada were included in the analysis. Based on occupational histories of study participants we measured SES using the International Socio-Economic Index of Occupational Status (ISEI) and the European Socio-economic Classification (ESeC). We divided the ISEI range into categories, using various criteria. Stratifying by gender, we calculated odds ratios (OR) and 95% confidence intervals (CI) by unconditional logistic regression, adjusting for age, study, and smoking behavior. We conducted analyses by histological subtypes of lung cancer and subgroup analyses by study region, birth cohort, education and occupational exposure to known lung carcinogens. The analysis dataset included 17,021 cases and 20,885 controls. There was a strong elevated OR between lung cancer and low SES, which was attenuated substantially after adjustment for smoking, however a social gradient persisted. SES differences in lung cancer risk were higher among men (lowest vs. highest SES category: ISEI OR 1.84 (95% CI 1.61-2.09); ESeC OR 1.53 (95% CI 1.44-1.63)), than among women (lowest vs. highest SES category: ISEI OR 1.54 (95% CI 1.20-1.98); ESeC OR 1.34 (95% CI 1.19-1.52)). SES remained a risk factor for lung cancer after adjustment for smoking behavior.

Night shift work, exposure to light at night (ALAN) and circadian disruption may increase the risk of hormone-dependent cancers. We evaluated the association of exposure to ALAN during sleeping time with breast and prostate cancer in a population based multicase-control study (MCC-Spain), among subjects who had never worked at night. We evaluated chronotype, a characteristic that may relate to adaptation to light at night. We enrolled 1,219 breast cancer cases, 1,385 female controls, 623 prostate cancer cases, and 879 male controls from 11 Spanish regions in 2008-2013. Indoor ALAN information was obtained through questionnaires. Outdoor ALAN was analyzed using images from the International Space Station (ISS) available for Barcelona and Madrid for 2012-2013, including data of remotely sensed upward light intensity and blue light spectrum information for each geocoded longest residence of each MCC-Spain subject. Among Barcelona and Madrid participants with information on both indoor and outdoor ALAN, exposure to outdoor ALAN in the blue light spectrum was associated with breast cancer [adjusted odds ratio (OR) for highest vs. lowest tertile, OR=1.47; 95% CI: 1.00, 2.17] and prostate cancer (OR=2.05; 95% CI: 1.38, 3.03). In contrast, those exposed to the highest versus lowest intensity of outdoor ALAN were more likely to be controls than cases, particularly for prostate cancer. Compared with those who reported sleeping in total darkness, men who slept in \"quite illuminated\" bedrooms had a higher risk of prostate cancer (OR=2.79; 95% CI: 1.55, 5.04), whereas women had a slightly lower risk of breast cancer (OR=0.77; 95% CI: 0.39, 1.51). Both prostate and breast cancer were associated with high estimated exposure to outdoor ALAN in the blue-enriched light spectrum. https://doi.org/10.1289/EHP1837.

Epidemiologic and animal data indicate that night shift work might increase the risk for breast cancer. We evaluated the association of night work with different clinical types of breast cancer in a population based case-control study (MCC-Spain study) taking into account chronotype, an individual characteristic that may relate to night shift work adaptation. Lifetime occupational history was assessed by face-to-face interviews and shift work information was available for 1708 breast cancer cases and 1778 population controls from 10 Spanish regions, enrolled from 2008 to 2013. We evaluated three shift work domains, including shift work type (permanent vs rotating), lifetime cumulative duration and frequency. We estimated odds ratios (OR) for night work compared to day work using unconditional logistic regression models adjusting for confounders. Having ever worked permanent or rotating night shift was associated with an increased risk for breast cancer compared to day workers [odds ratio (OR) 1.18; 95 % CI 0.97,1.43]. Chronotype was differentially associated with breast cancer depending on the duration of night shift work. Risk was higher in women with invasive tumors (OR 1.23; 95 % CI 1.00, 1.51) and for estrogen and progestagen positive tumors among premenopausal women (OR 1.44; 95 % CI 1.05, 1.99). Having ever performed night shift was associated with a small increased risk for breast cancer and especially in subgroups of women with particular hormone related characteristics.