Neurodevelopmental effects of low-level prenatal mercury exposure from maternal fish consumption in a Mediterranean cohort: study rationale and design.

BACKGROUND: Mercury is a neurotoxic environmental pollutant. However, the literature on the neurodevelopmental effect of low-level prenatal mercury exposure from maternal fish intake is inconsistent. We assessed the association between prenatal mercury exposure and infant neurodevelopment in coastal areas of 4 Mediterranean countries. METHODS: This was a prospective cohort study that planned to enroll approximately 1700 mother-infant pairs. Pregnant women and their newborn children were recruited in selected hospitals of the study areas. Biological samples, including maternal hair and cord blood, were collected from mothers and children, and the concentrations of mercury and other elements were measured. Exposures to lifestyle, environmental, and social factors were assessed through questionnaires. The main outcome was child neurodevelopment at 18 months, as measured by the Bayley Scales of Infant and Toddler Development, Third Edition. CONCLUSIONS: This cohort has a number of strengths. First, mercury concentration was measured in several biological samples, which allows for a better understanding of mercury kinetics and is useful for sensitivity analyses. Therefore, we expect to be able to adjust for the potential confounding effects of lifestyle and social factors and for the effects of other elements that were measured in the biological samples. Finally, this is a multinational study and thus permits assessment of the relation between mercury and child neurodevelopment in different populations.

Nutrient Intake during Pregnancy and Adherence to Dietary Recommendations: The Mediterranean PHIME Cohort.

Few studies provide a detailed description of dietary habits during pregnancy, despite the central role of nutrition for the health of the mother and offspring. This paper describes the dietary habits, energy and nutrient intake in pregnant women from four countries belonging to the Mediterranean PHIME cohort (Croatia, Greece, Italy and Slovenia) and evaluates their adherence to the European Food Safety Authority (EFSA) recommendations. A total of 1436 women were included in the present analysis. Maternal diet was assessed using a food frequency questionnaire (FFQ). The mean macro and micronutrient intakes were estimated and compared with the dietary reference values (DRVs). The percentage distribution of the 16 food groups in the total intake of each macronutrient was estimated. All women shared a similar diet during pregnancy; almost all the women in the four countries exceeded the DRV for sugars, and the total fat intake was above the DRV in most women in all the countries, as was the contribution of saturated fatty acids (SFAs) to the total energy intake. In all four countries, we observed an increased risk of micronutrient deficiency for iron, folate and vitamin D. Shared guidelines, implemented at both the national and European level, are essential to improve the maternal nutritional status during pregnancy.

Clinical features and natural history of physical urticaria in children.

Physical triggers are the most common precipitating factors for chronic urticaria in childhood. We investigate the natural history of physical urticaria (PU) and attempt to identify prognostic features. A retrospective study covering a 3 yr period (1999-2002) identified 82 children with PU seen in a tertiary referral centre. Parents of 53 children with PU responded to follow up by questionnaire and were included in the data analysis. The questionnaire ascertained symptom severity, remission status, effects of treatment and prognostic factors in determining resolution of the urticaria. Not all parents answered every question. Fisher's exact test was used to compare the remission and non-remission groups and Kaplan-Meir survival analysis was used to derive estimates of time to achieve remission. All 53 children with PU had chronic urticaria, with dermatographic, cholinergic and mixed subtypes of PU forming over 70% of the subtypes. Overall, 13% (6/45) of the children reported respiratory symptoms with the episodes of urticaria, and 67% (35/52) reported associated angioedema. In univariate analysis, a history of other allergic conditions in the child was associated with a greater chance of non-remission (p = 0.007). No significant difference in the age of onset of urticaria and duration of individual bouts was noted between the remission and non-remission groups. Episodes of urticaria were significantly less frequent (p = 0.02) in the remission group (monthly/weekly/daily - 70%/30%/0%) than the non-remission group (38%/34%/28%). Among the 20 children achieving remission, on average this occurred 30 months after onset of symptoms. In the survival analysis, the number of children becoming urticaria free was 11.6% (95% CI: 5.4%-23.9%) at 1 yr post-onset and 38.4% (95% CI: 25.9%-54.3%) 5 yr post-onset. In conclusion, based on this selected tertiary population, the prognosis for PU may not be as benign as has previously been reported. A history of allergic conditions and more frequent episodes of urticaria were associated with a poorer prognosis.

CYP3A genes and the association between prenatal methylmercury exposure and neurodevelopment.

BACKGROUND: Results on the association between prenatal exposure to methylmercury (MeHg) and child neuropsychological development are heterogeneous. Underlying genetic differences across study populations could contribute to this varied response to MeHg. Studies in Drosophila have identified the cytochrome p450 3A (CYP3A) family as candidate MeHg susceptibility genes. OBJECTIVES: We evaluated whether genetic variation in CYP3A genes influences the association between prenatal exposure to MeHg and child neuropsychological development. METHODS: The study population included 2639 children from three birth cohort studies: two subcohorts in Seychelles (SCDS) (n=1160, 20 and 30months of age, studied during the years 2001-2012), two subcohorts from Spain (INMA) (n=625, 14months of age, 2003-2009), and two subcohorts from Italy and Greece (PHIME) (n=854, 18months of age, 2006-2011). Total mercury, as a surrogate of MeHg, was analyzed in maternal hair and/or cord blood samples. Neuropsychological development was evaluated using Bayley Scales of Infant Development (BSID). Three functional polymorphisms in the CYP3A family were analyzed: rs2257401 (CYP3A7), rs776746 (CYP3A5), and rs2740574 (CYP3A4). RESULTS: There was no association between CYP3A polymorphisms and cord mercury concentrations. The scores for the BSID mental scale improved with increasing cord blood mercury concentrations for carriers of the most active alleles (ß[95% CI]:=2.9[1.53,4.27] for CYP3A7 rs2257401 GG+GC, 2.51[1.04,3.98] for CYP3A5 rs776746 AA+AG and 2.31[0.12,4.50] for CYP3A4 rs2740574 GG+AG). This association was near the null for CYP3A7 CC, CYP3A5 GG and CYP3A4 AA genotypes. The interaction between the CYP3A genes and total mercury was significant (p<0.05) in European cohorts only. CONCLUSIONS: Our results suggest that the polymorphisms in CYP3A genes may modify the response to dietary MeHg exposure during early life development.

Reduction in bioavailability of 6-mercaptopurine on simultaneous administration with cow's milk.

The authors present a case where the simultaneous administration of 6-mercaptopurine (6-MP) and cow's milk during maintenance treatment for acute lymphoblastic leukemia led to elevated full blood counts resistant to increasing doses of chemotherapy. The blood counts returned to the expected range after milk intake with chemotherapy was discontinued.

Assessing Peanut Consumption in a Population of Mothers and Their Children in the UK.

BACKGROUND: Food frequency questionnaires (FFQs) are essential tools to investigate the relationship between peanut consumption and the development of peanut allergy. The aim was to validate a 50-item FFQ for use in peanut protein sensitization studies. METHODS: There were 38 mother-child pairs visiting a pediatric clinic of a London hospital included. Mothers recorded their own and their child's diet, using a 7 day food diary (7DFDR), completed prospectively over week. Six months later, they tried to recall the consumption of food items for the index week on a FFQ. RESULTS: Of these, 33 out of 38 mothers completed both the 7DFDR and the recall FFQ. Although there was considerable variation at the individual level between the 2 tools, there was extremely close agreement between the mean 7DFDR response and the FFQ when considering groups of fives with similar FFQ levels. Agreement was apparent on both peanut and other control foods consumption patterns. CONCLUSION: The FFQ will reliably divide the population into groups with markedly different peanut consumption levels. It accurately reflects true adults and children peanut consumption, especially at low levels of peanut consumption, as it was validated against the gold standard, the 7DFDR. It also provides a good measure of other foods consumption.