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.

Effect of levetiracetam monotherapy on lipid profiles and thyroid hormones in children with epilepsy: A prospective study.

Long-term treatment with some older antiepileptic drugs may lead to dyslipidemia or thyroid disturbances. The effect of levetiracetam (LEV), a newer broad spectrum antiepileptic agent, on cardiovascular risk factors is not yet sufficiently investigated. The purpose of this study was to investigate prospectively the effect of LEV monotherapy on serum lipid profile and thyroid hormones levels in children with epilepsy. The study population consisted of 39 children (21 females, 18 males, mean age 6.8 ± 4,1 years, range 2-15 years) that were treated for new-onset epilepsy with LEV monotherapy. Serum total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TGs), apolipoprotein A-I (apo A-I), apolipoprotein B (apo B), lipoprotein (a) [Lp(a)], thyroxine (T4), free thyroxine (FT4) and thyrotropin (TSH), were evaluated before and at 6 and 12 (n = 28) months of LEV monotherapy. TGs were significantly decreased at 6 and 12 months of LEV treatment (p = 0.026 and p = 0.001, respectively). TGs/HDL-C ratio was significantly decreased at 6 and 12 months of LEV treatment (p = 0.024 and p = 0.003, respectively), while LDL-C/HDL-C ratio was significantly decreased at 12 months of LEV treatment (p = 0.025). There were no significant alterations in the other parameters during the study. In conclusion, long-term LEV monotherapy does not cause adverse alterations on thyroid hormones and serum lipids in children with epilepsy. More studies are needed to clarify whether LEV monotherapy have a favourable effect on serum lipids and whether LEV may be considered as a safer alternative drug for the prevention of antiepileptic drug-induced cardiovascular complications in adult life.

Long-term effect of levetiracetam monotherapy on haematological parameters in children with epilepsy: A prospective study.

Studies evaluating the effect of Levetiracetam (LEV) on haematological parameters in patients with epilepsy are very limited. Short-term effects on haematological parameters in children with epilepsy, at 2 and 6 months of LEV treatment, have been previously reported in the literature. Purpose of the current study was to further investigate the long-term changes on haematological parameters in children with epilepsy during LEV monotherapy. White blood cell, neutrophils, lymphocytes, monocytes, haemoglobin, haematocrit, mean corpuscular volume, mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration and platelets were measured in 20 children (11 females, mean age 6,5 ±â€¯4,4 years, range 2-15 years) with epilepsy, before and after 12 months of LEV monotherapy. Lymphocyte count was significantly decreased at 12 months (p = 0.003) of LEV treatment. Three children (15%) at 12 months of treatment had lymphocyte count below 10th percentile for age. Neutrophils counts were significantly increased and platelets counts were significantly decreased at 12 months of treatment (p = 0.046 and p = 0.006, respectively). In addition, haematocrit and mean corpuscular volume were significantly increased at 12 months of treatment (p = 0.036 and p = 0.031, respectively). There were no significant alterations in the other parameters evaluated during the study. No association was found between all parameters and LEV dosage (mg/kg) at 12 months of treatment. Large, prospective studies are needed to investigate the clinical significance of the above haematological changes and whether these parameters should be monitored periodically in children taking LEV.

Polymorphisms in ABC transporter genes and concentrations of mercury in newborns--evidence from two Mediterranean birth cohorts.

BACKGROUND: The genetic background may influence methylmercury (MeHg) metabolism and neurotoxicity. ATP binding cassette (ABC) transporters actively transport various xenobiotics across biological membranes. OBJECTIVE: To investigate the role of ABC polymorphisms as modifiers of prenatal exposure to MeHg. METHODS: The 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 (ß = -0.29, 95%CI -0.47, -0.12) and TT (ß = -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 (ß = -0.12, 95%CI -0.33, 0.09), and TT (ß = -0.28, 95%CI -0.51, -0.06) versus CC. For rs2273697, the interaction coefficient was positive when combining GA+AA (ß = 0.16, 95%CI 0.01, 0.32) versus GG. CONCLUSION: The ABC transporters appear to play a role in accumulation of MeHg during early development.