ALAD and APOE polymorphisms are associated with lead and mercury levels in Italian pregnant women and their newborns with adequate nutritional status of zinc and selenium.

The impacts of single-nucleotide polymorphisms (SNPs) in ALAD and VDR genes on Pb health effects and/or kinetics are inconclusive at low exposure levels, while studies including APOE SNPs are rare. In this study, we examined the associations of ALAD, VDR and APOE SNPs with exposure biomarkers of Pb and other trace elements (TEs) in Italian pregnant women (N = 873, aged 18-44 years) and their newborns (N = 619) with low-level mixed-element exposure through diet, the environment or endogenously. DNA from maternal peripheral venous blood (mB), sampled during the second and third trimesters, was genotyped for ALAD (rs1800435, rs1805313, rs1139488, rs818708), VDR (rs2228570, rs1544410, rs7975232, rs731236) and APOE (rs429358, rs7421) using TaqMan SNP assays. Personal and lifestyle data and TE levels (mB, maternal plasma, hair and mixed umbilical cord blood [CB]) from the PHIME project were used. Multiple linear regression models, controlling for confounding variables, were performed to test the associations between SNPs and TEs. The geometric means of mB-Pb, mB-Hg, mB-As and mB-Cd (11.0 ng/g, 2.16 ng/g, 1.38 ng/g and 0.31 ng/g, respectively) indicated low exposure levels, whereas maternal plasma Zn and Se (0.72 µg/mL and 78.6 ng/g, respectively) indicated adequate micronutritional status. Variant alleles of ALAD rs1800435 and rs1805313 were negatively associated with mB-Pb levels, whereas a positive association was observed for rs1139488. None of the VDR SNPs or their haplotypes had any association with Pb levels. Regarding APOE, the ϵ4 allele was associated with lower mB-Hg and CB-Hg, while a positive association was found with the ϵ2 allele and CB-Pb when the model included only newborn girls. The observed associations indicate possible modification effects of ALAD and APOE SNPs on Pb or Hg kinetics in women and their newborns with low exposure to non-essential TEs, as well as an adequate nutritional status of Zn and Se.

Dietary Intake of the Italian PHIME Infant Cohort: How We Are Getting Diet Wrong from as Early as Infancy.

Unhealthy dietary habits established in early infancy may lead to under or over nutrition later in life. This paper describes the energy, nutrients and food-type intake of 18-month-old infants belonging to the Italian PHIME cohort (n = 389) and evaluates adherence to the Italian dietary reference values (DRVs). Infant dietary data were collected using 7-day dietary records. Mean energy, macro and micronutrient intakes were estimated and compared with the DRVs. The percentage contribution of 19 selected food groups to total energy and macro- and micronutrient intake was determined with the aim of establishing the main food sources. Most infants' diet shared common characteristics: poor variety, excessive intake of proteins (16.5 E% vs. 8-12 E% DRV) and saturated fatty acids (SFAs) (13.8 E% vs. <10 E% DRV), mainly derived from milk and dairy products, and low intake of total fats (33.2 E% vs. 35-40 E% DRV), polyunsaturated fatty acids (PUFAs) (3.1 E% vs. 5-10 E% DRV), vitamin D (1.1 vs. 15 µg/day DRV) and iron (4.5 vs. 8 mg/day DRV). The unbalanced distribution of macronutrients was reflected in energy intakes outside DRV ranges for more than half the infants. Public health interventions promoting healthy eating habits from early on, even from pregnancy, could yield significant short- and long-term health benefits.

Quality of maternal and newborn hospital care in Brazil: a quality improvement cycle using the WHO assessment and quality tool.

BACKGROUND: Increasing efforts toward quality improvement (QI) are necessary in low- and middle-income countries (LMICs) to reduce maternal and perinatal mortality and morbidity and to promote respectful care. In Brazil, perinatal health indicators are below targets in several states despite universal access to perinatal services and very high rates of institutional births, indicating poor quality of care (QoC) as a key issue to be addressed. However, research efforts to develop and test QoC improvement interventions are scarce. OBJECTIVES: We assessed the effects of a 1-year comprehensive QI cycle using a World Health Organization (WHO) assessment and quality tool on maternal and newborn care at hospital level and documented QIs obtained after a 1-year comprehensive QI cycle. METHODS: Uncontrolled, unblinded, pre-post study carried out in six maternity hospitals in Pernambuco, Brazil, accounting for 29 128 live births in 2014. A standards-based and participatory approach based on a WHO quality assessment and improvement tool for maternal and neonatal care at hospital level was used. A national team of assessors supervised by international experts carried out baseline and final assessments. An action plan was developed and implemented to address key quality gaps emerging from the baseline assessment and from two supportive supervision visits. RESULTS: At baseline, hospitals presented a variety of quality gaps, the majority common to all participating centers. Gaps in case management of normal and complicated deliveries and in respectful and holistic care were predominant, in both teaching/tertiary and secondary care hospitals. After one year, several improvements were observed, particularly in respectful care during labor and at delivery, in case management of normal labor and delivery and in neonatal care. CONCLUSIONS: A systematic participatory approach based on a WHO tool produced important QIs in a relatively short time and should be considered for use for large-scale QI programs in Brazil and other LMICs. Its comprehensive, peer-to-peer and action-oriented nature and its capability to document QI over time and to build a QI culture represent important comparative advantages over other QI interventions.

The role of mercury, selenium and the Se-Hg antagonism on cognitive neurodevelopment: A 40-month follow-up of the Italian mother-child PHIME cohort.

Despite a 15-year long effort to define the "safety" of fish intake during pregnancy, there remains still uncertainty on this important public health issue. The evaluation of the toxic effects of contaminants, particularly mercury (Hg) in fish-eating populations is complicated by the fact that sea-food is also rich in beneficial nutrients, such as selenium (Se). There is toxicological plausibility of an antagonistic effects between Se and Hg, and some theoretical support for the inclusion of the Se-Hg interaction to better assess the risk linked with fish intake. To assess the effects of exposure to low-level Hg through fish consumption on the developing brain and the interaction between Hg and Se, we conducted an analysis at age 40 months in Italian children, enrolled in a prospective mother-child cohort, comparing additive and multiplicative models. Participant subjects were the 470 children born within the Northern Adriatic Cohort II (NAC-II) cohort who were tested by using the Bayley Scales of Infant and Toddler Development third edition (Bayley-III) (BSID-III) at age 40. Family demographic and socioeconomic information, pregnancy and delivery history, parental and child medical history and food consumption were assessed through questionnaires. Maternal blood samples were collected during pregnancy, cord blood at birth and maternal milk 1 month after delivery. As other exposures of interest, we considered the level of Se in maternal and cord blood and in breast milk and the potential Se-Hg antagonism. Se and inverse of THg (1:THg) concentrations were categorized according to the tertiles of their distributions, in low, medium and high levels of exposure. The lower end of the composite cognitive score distribution closest to 20% was defined as suboptimal development. Multiple logistic regression were applied to assess the association between the dichotomized composite cognitive score and the categorized exposure to Se and 1:THg, and the antagonism between Se and 1:THg. In the recruiting period, 900 pregnant women were enrolled in the cohort; 767 of these remained in the study at delivery and 470 children at 40 months. After excluding preterm births, 456 children were used in the final analyses. The larger difference in risk for suboptimal neurodevelopment was observed for the category with High THg and Low Se with OR = 2.55 (90% CI 1.02; 6.41) under the multiplicative and OR = 1.33 (90% CI 0.80; 1.87) under the additive model. The category High THg and High Se showed a very slightly better fit of the additive model (OR = 1.07, 90% CI 0.65; 1.50) versus the multiplicative (OR = 1.66, 90% CI 0.73; 1.77). A negative - antagonistic - interaction term for this category was estimated under the multiplicative model giving an OR = 1.17 (90% CI 0.42; 3.28). Although this evidence of the effects of the Se-Hg antagonism on the children neuro-development needs to be confirmed, if Se can counterbalance Hg toxicity, the evaluation of the effect on human health of fish consumption, should also consider the diverse ratios between Se and Hg concentration in different fish species.

Mercury, arsenic and selenium exposure levels in relation to fish consumption in the Mediterranean area.

In order to assess mercury (Hg), selenium (Se) and arsenic (As) exposure in the Mediterranean area, total mercury (THg), monomethylmercury (MeHg), Se and As levels were measured in umbilical cord blood and breast milk from Italian (n=900), Slovenian (n=584), Croatian (n=234) and Greek (n=484) women. THg, MeHg, As, and Se levels were also determined in blood samples of the same mothers from Italy and Croatia. In addition, THg and MeHg were determined in the same women's hair from all the countries involved in this study and As and Se levels were determined in the mother's urine samples from Italy, Croatia and Greece. Besides recording the consumption of other food items, the frequencies of fish consumption were assessed by detailed food frequency questionnaires, since fish represents an important source of Hg, Se and As in humans. The highest levels of THg and As were found in cord blood (Med((THg))=5.8 ng/g; Med((As))=3.3 ng/g) and breast milk (Med((THg))=0.6 ng/g; Med((As))=0.8 ng/g) from Greek women, while the highest Se levels were found in cord blood (Med=113 ng/g) from Italy. Significant linear correlations were found between Hg, Se and As in blood, cord blood and breast milk. In addition, significant relations were found between the frequencies of total fish consumption and biomarkers of As, MeHg and Se exposure, with the strongest Spearman rank coefficients between frequencies of total fish consumption and THg levels in cord blood (r(s)=0.442, p<0.001) or THg levels in hair (r(s)=0.421, p<0.001), and between frequencies of total fish consumption and As levels in cord blood (r(s)=0.350, p<0.001). The differences in Hg and As exposure between countries were probably due to different amounts of fish consumption and the consumption of different species of fish of different origin, while the highest Se levels in women from Italy were probably the consequence of the more frequent consumption of different non specific food items. Moreover, fish consumption, the possible common source of As, Hg and Se intake, could explain the correlations between the elements determined in cord blood, mother's blood or breast milk.

Maternal diet and selenium concentration in human milk from an Italian population.

BACKGROUND: Low selenium (Se) status is associated with several diseases. International organizations have proposed intakes of Se for general populations, including infants. Studies of the association of Se concentration in breast milk and maternal diet have yielded inconsistent results. We evaluated the relation between the intake of food items during pregnancy and Se concentration in human milk after delivery and compared infant intake of Se from breast milk with the recommended intakes. METHODS: This cross-sectional study was part of the baseline assessment of a prospective cohort of Italian mother-child pairs enrolled in 1999-2001. Se concentration was measured in the milk of 100 women included in the cohort and correlated with the intake of food items during pregnancy and lactation as reported in a food frequency questionnaire. RESULTS: Among foods consumed in pregnancy, only eggs had a positive, but weak, correlation with Se concentration in milk (r = 0.20, P = 0.04). Fish intake during lactation was also weakly correlated with Se in milk (r = 0.21, P = 0.04). Se content of breast milk in our population was lower than that noted in other international studies; however, very few children who were exclusively breastfed were estimated not to have met the recommended Se intake. CONCLUSIONS: Future research should aim to verify whether infants in this part of Italy still meet the recommended nutrient intake of Se and to assess the influence of the concurrent diet of lactating mothers on the Se content of their milk.

[Fetal and perinatal exposure to mercury and selenium: baseline evaluation of a cohort of children in Friuli Venezia Giulia, Italy]. / Esposizione fetale e perinatale a mercurio e selenio: valutazione alla baseline di una coorte di bambini del Friuli Venezia Giulia.

OBJECTIVE: neurotoxicity of prenatal exposure to high concentrations of mercury (Hg) is well known; however, the doseresponse relationship at low exposure levels has not been quantified yet. This article illustrates the measurement of prenatal exposure to Hg and the pathway of exposure through the diet in Friuli Venezia Giulia, Italy. DESIGN: description of a prospective cohort at the baseline. SETTING AND PARTICIPANTS: 242 mother- infant pairs living in Friuli Venezia Giulia were enrolled between 1999 and 2001. MAIN OUTCOME MEASURES: We measured the concentrations of Hg in the hair of mothers and children and of Hg and selenium (Se) in breast milk. The diet during pregnancy was estimated through a food frequency questionnaire (FFQ) with a detailed section regarding fish. We calculated the correlations between Hg and Se in the biological samples and estimated the association between Hg concentrations and fish consumption. RESULTS: in general, Hg levels in hair and milk were positively associated with the consumption of fish from the lagoon of Grado and Marano. However, they were low in comparison with those of other fish-eating populations and below theWHO alert limits, likely because of the small consumption of fish among pregnant women, estimated from the FFQ. The concentration of Se in milk was also smaller than that reported in other international studies. CONCLUSION: in Friuli Venezia Giulia, fetal and perinatal Hg exposure is low. The children of the cohort will be followed- up at school age to measure possible neurodevelopmental effects of such low exposures to Hg.

Asthma symptoms, lung function, and markers of oxidative stress and inflammation in children exposed to oil refinery pollution.

OBJECTIVES: Little is known about the effects of exposure to petroleum refinery emissions on respiratory health in children. We evaluated lung function and markers of inflammation and oxidative stress in children and adolescents with and without asthma or wheezing symptoms living in a petrochemical polluted area (Sarroch, Sardinia) versus a reference area (Burcei). METHODS: Parents of 275/300 6- to 14-year-old children living in Sarroch and parents of 214/323 children living in Burcei answered a questionnaire on respiratory symptoms and risk factors. Measurements of forced expiratory volume after 1 second (FEV(1)) and of forced expiratory flow rates at 25-75% of vital capacity (FEF(25-75)) were available in 27 and 23 asthma/wheezing-positive subjects and in 7 and 54 asthma/wheezing-negative subjects in Sarroch and in Burcei, respectively; for fractional exhaled nitric oxide (FE(NO)) corresponding figures were 27 and 24 and 8 and 55 in Sarroch and in Burcei, respectively. Malondialdehyde-deoxyguanosine (MDA-dG) adduct levels in nasal mucosa were measured in 12- to 14-year-old adolescents (8 and 14 asthma/wheezing-positive and 20 and 28 asthma/wheezing-negative subjects in Sarroch and in Burcei, respectively). Air pollutants were assessed during 3 weeks, starting 1 week before lung function, FE(NO), and MDA-dG measurements. Generalized linear models were used to estimate the effect of the area of residence adjusting for confounders. RESULTS: Weekly average concentrations of sulfur dioxide were 6.9-61.6 µg/m(3) in Sarroch versus 0.3-7.6 µg/m(3) in the rural area of Burcei; of nitrogen dioxide, 5.2-28.7 µg/m(3) versus 1.7-5.3 µg/m(3); and of benzene, 1.8-9.0 µg/m(3) versus 1.3-1.5 µg/m(3), respectively. Children living in Sarroch versus children living in the reference area showed an increase in wheezing symptoms {adjusted prevalence ratio=1.70 [90% confidence interval (CI)=1.01; 2.86]}; a decrease in lung function [variation in FEV(1)=-10.3% (90% CI=-15.0; -6.0%) and in FEF(25-75)=-12.9% (90% CI=-20.7; -4.3%)]; an increase in bronchial inflammation [variation in FE(NO)=+35% (90% CI=11.7; 80.1%)]; and an increase in MDA-dG adducts of +83% (90% CI=22.9; 174.1%). CONCLUSIONS: Data from this small study are consistent with the role of environmental pollutants on lung function and inflammation.