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.

BackgroundMercury 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.MethodsThis 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.ConclusionsThis 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.

BackgroundThe genetic background may influence methylmercury (MeHg) metabolism and neurotoxicity. ATP binding cassette (ABC) transporters actively transport various xenobiotics across biological membranes.ObjectiveTo investigate the role of ABC polymorphisms as modifiers of prenatal exposure to MeHg.MethodsThe study population consisted of participants (n = 1651) in two birth cohorts, one in Italy and Greece (PHIME) and the other in Spain (INMA). Women were recruited during pregnancy in Italy and Spain, and during the perinatal period in Greece. Total mercury concentrations were measured in cord blood samples by atomic absorption spectrometry. Maternal fish intake during pregnancy was determined from questionnaires. Polymorphisms (n = 5) in the ABC genes ABCA1, ABCB1, ABCC1 and ABCC2 were analysed in both cohorts.Results ABCB1 rs2032582, ABCC1 rs11075290, and ABCC2 rs2273697 modified the associations between maternal fish intake and cord blood mercury concentrations. The overall interaction coefficient between rs2032582 and log2-transformed fish intake was negative for carriers of GT (β = −0.29, 95%CI −0.47, −0.12) and TT (β = −0.49, 95%CI −0.71, −0.26) versus GG, meaning that for a doubling in fish intake of the mothers, children with the rs2032582 GG genotype accumulated 35% more mercury than children with TT. For rs11075290, the interaction coefficient was negative for carriers of TC (β = −0.12, 95%CI −0.33, 0.09), and TT (β = −0.28, 95%CI −0.51, −0.06) versus CC. For rs2273697, the interaction coefficient was positive when combining GA+AA (β = 0.16, 95%CI 0.01, 0.32) versus GG.ConclusionThe ABC transporters appear to play a role in accumulation of MeHg during early development.

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 30 months of age, studied during the years 2001–2012), two subcohorts from Spain (INMA) (n=625, 14 months of age, 2003–2009), and two subcohorts from Italy and Greece (PHIME) (n=854, 18 months of age, 2006–2011). Total mercury, as a surrogate of MeHg, was analysed 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 analysed: 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 (β[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.