Long-term exposure to methylmercury and psychiatric symptoms in residents of Minamata, Japan

Introduction: It is well-known that prenatal or postnatal exposure to methylmercury can produce neurological signs in adults and children, exemplified by a case of large-scale poisoning in Minamata, Japan, in the 1950s. However, evidence regarding whether pre- or postnatal exposure to methylmercury causes psychiatric symptoms (e.g., impairment of intelligence and mood and behavioral dysfunction) is still limited-excluding cases of fetal Minamata disease patients. Methods: We evaluated the effects of pre- or postnatal exposure to methylmercury on psychiatric symptoms using data derived from a 1971 population-based survey in Minamata and neighboring communities. We adopted residential areas as an exposure indicator and psychiatric symptoms as the outcome. Then, we estimated the adjusted prevalence odds ratio (POR) and confidence interval (Cl) of psychiatric symptoms in relation to residential area. Results: There were 904 participants in Minamata (high exposure area), 1700 in Goshonoura (middle exposure area), and 913 in Ariake (low exposure area). Compared to the Ariake area, participants in the Minamata area manifested psychiatric symptoms more frequently: PORs for impairment of intelligence and mood and behavioral dysfunction were 5.2 (95% Cl: 3.7-7.3) and 4.4 (95% Cl: 2.9-6.7), respectively. Furthermore, participants with psychiatric symptoms in the Minamata area more frequently had neurological signs. Peaks in prevalence of psychiatric symptoms occurred around age 20 and in older age adults in the area. These findings did not change when we excluded those who had been officially certified as Minamata disease patients by that time. Conclusions: The present study suggests a relationship between pre- or postnatal exposure to methylmercury and psychiatric symptoms among the general population in Minamata even after excluding officially certified patients

Prenatal exposure to maternal infections or immune response and the offspring's risk for mental disorders : a review

The objective of this review is to summarize the current scientific evidence on the effect of prenatal exposure to maternal infection and immune response on the offspring's risk for mental disorders. Studies were searched from PubMed database with the following keywords: Mental Disorders AND Prenatal Exposure Delayed Effects AND Infection AND Inflammation. Prenatal exposure to maternal influenza appears to increase the offspring's risk for schizophrenia spectrum disorders, although the studies are not fully consistent. Prenatal exposure to maternal fever seems to be related with elevated autism risk in the offspring. No replicated findings of an association between prenatal infectious exposure and other mental disorders exist. Evidence for the effect of prenatal exposure to maternal infection on risk for mental disorders exists for several different infections, and it is likely that the genetic liability to these disorders operate in conjunction with the exposure. Therefore, genetically sensitive study designs are needed

Maternal pre-pregnancy obesity and timing of puberty in sons and daughters: a population-based cohort study.

BackgroundIn many countries, an increased prevalence of obesity in pregnancy has coincided with a declining pubertal age. We aimed to explore the potential effect of maternal pre-pregnancy overweight and obesity on timing of puberty in sons and daughters.MethodsBetween 2012 and 2018, 15 819 of 22 439 invited children from the Danish National Birth Cohort, born 2000-03, provided half-yearly information from the age of 11 years on the pubertal milestones: Tanner stages, voice break, first ejaculation, menarche, acne and axillary hair. We estimated adjusted mean monthly differences (with 95% confidence intervals) in age at attaining the pubertal milestones for children exposed to maternal pre-pregnancy obesity [body mass index (BMI) ≥30.0 kg/m2] or overweight (BMI 25.0 to 29.9 kg/m2) with normal weight (BMI 18.5 to 24.9 kg/m2) as reference. In mediation analysis, we explored whether childhood BMI at age 7 years mediated the associations.ResultsMaternal pre-pregnancy obesity was associated with earlier age at attaining most pubertal milestones in sons, and pre-pregnancy overweight and obesity were associated with earlier age at attaining all pubertal milestones in daughters. When combining all pubertal milestones, pre-pregnancy obesity [sons: -1.5 (-2.5, -0.4) months; daughters: -3.2 (-4.2, -2.1) months] and overweight [daughters only: -2.6 (-3.3, -1.8) months] were associated with earlier timing of puberty. The associations in sons were completely mediated by higher childhood BMI and partly so in daughters.ConclusionsMaternal pre-pregnancy obesity appears to lower timing of puberty through childhood obesity in sons and mainly through other mechanisms in daughters

Separation of Risks and Benefits of Seafood Intake

Background: Fish and seafood provide important nutrients but may also contain toxic contaminants, such as methylmercury. Advisories against pollutants may therefore conflict with dietary recommendations. In resolving this conundrum, most epidemiologic studies provide little guidance because they address either nutrient benefits or mercury toxicity, not both. Objectives: Impact on the same health outcomes by two exposures originating from the same food source provides a classical example of confounding. To explore the extent of this bias, we applied structural equation modeling to data from a prospective study of developmental methylmercury neurotoxicity in the Faroe Islands. Results: Adjustment for the benefits conferred by maternal fish intake during pregnancy resulted in an increased effect of the prenatal methylmercury exposure, as compared with the unadjusted results. The dietary questionnaire response is likely to be an imprecise proxy for the transfer of seafood nutrients to the fetus, and this imprecision may bias the confounder-adjusted mercury effect estimate. We explored the magnitude of this bias in sensitivity analysis assuming a range of error variances. At realistic imprecision levels, mercury-associated deficits increased by up to 2-fold when compared with the unadjusted effects. Conclusions: These results suggest that uncontrolled confounding from a beneficial parameter, and imprecision of this confounder, may cause substantial underestimation of the effects of a toxic exposure. The adverse effects of methylmercury exposure from fish and seafood are therefore likely to be underestimated by unadjusted results from observational studies, and the extent of this bias will be study dependent

Prevalence of Prenatal Brain Abnormalities in Fetuses with Congenital Heart Disease: Systematic Review.

OBJECTIVES: Studies have demonstrated an association between congenital heart defects (CHD) and postnatal brain abnormalities and neurodevelopmental delay. Recent evidence suggests that some of these brain abnormalities are present even before birth. The primary aim of this study was to perform a systematic review to quantify the prevalence of prenatal brain abnormalities in fetuses with CHD. METHODS: MEDLINE, EMBASE and The Cochrane Library were searched. Reference lists within each article were hand-searched for additional reports. The outcomes included structural brain abnormalities (MRI), changes in brain volume (MRI, 3-D volumetric MRI, 3-D ultrasound and Phase Contrast Magnetic Resonance), metabolism or maturation (Magnetic Resonance Spectroscopy and Phase Contrast Magnetic Resonance) and blood flow (Doppler ultrasound, Phase Contrast Magnetic Resonance and 3D Power Doppler ultrasound) in fetuses with CHD. Cohort and case-control studies were included. Cases of chromosomal or genetic abnormalities, case reports and editorials were excluded. Proportion meta-analysis was used for analysis. Between-study heterogeneity was assessed using the I(2) test (Registration number: CRD42015025546). RESULTS: The search yielded 1,943 citations; and 20 studies were included in the review (n = 1175 cases, 221 in the meta-analysis). Three studies reported data on structural brain abnormalities, while data on altered brain volume, metabolism and blood flow were reported in 7, 3 and 14 studies, respectively. The three studies reporting data on structural brain abnormalities were suitable for inclusion in a meta-analysis (221 cases). The prevalence of prenatal structural brain abnormalities in fetuses with CHD was 28% (95% CI 18%-40%), similar prevalence in fetuses with tetralogy of Fallot of 25% (95% CI 14%-39). These abnormalities included ventriculomegaly (commonest), agenesis of the corpus callosum, ventricular bleeding, increased extra-axial space, vermian hypoplasia, white matter abnormalities and delayed brain development. Fetuses with CHD were more likely, than those without CHD, to have reduced brain volume, delay in brain maturation and altered brain circulation, most commonly in the form of reduced middle cerebral artery pulsatility index and cerebroplacental ratio. These changes are usually evident in the third trimester, but some studies have reported them as early as the second trimester. CONCLUSIONS: In the absence of known major aneuploidy or genetic syndromes, fetuses with CHD are at increased risk of brain abnormalities, which are present antenatally

Methylmercury neurotoxicity in Amazonian children downstream from gold mining.

In widespread informal gold mining in the Amazon Basin, mercury is used to capture the gold particles as amalgam. Releases of mercury to the environment have resulted in the contamination of freshwater fish with methylmercury. In four comparable Amazonian communities, we examined 351 of 420 eligible children between 7 and 12 years of age. In three Tapajós villages with the highest exposures, more than 80% of 246 children had hair-mercury concentrations above 10 microg/g, a limit above which adverse effects on brain development are likely to occur. Neuropsychological tests of motor function, attention, and visuospatial performance showed decrements associated with the hair-mercury concentrations. Especially on the Santa Ana form board and the Stanford-Binet copying tests, similar associations were also apparent in the 105 children from the village with the lowest exposures, where all but two children had hair-mercury concentrations below 10 microg/g. Although average exposure levels may not have changed during recent years, prenatal exposure levels are unknown, and exact dose relationships cannot be generated from this cross-sectional study. However, the current mercury pollution seems sufficiently severe to cause adverse effects on brain development

Separation of Risks and Benefits of Seafood Intake

BACKGROUND: Fish and seafood provide important nutrients but may also contain toxic contaminants, such as methylmercury. Advisories against pollutants may therefore conflict with dietary recommendations. In resolving this conundrum, most epidemiologic studies provide little guidance because they address either nutrient benefits or mercury toxicity, not both. OBJECTIVES: Impact on the same health outcomes by two exposures originating from the same food source provides a classical example of confounding. To explore the extent of this bias, we applied structural equation modeling to data from a prospective study of developmental methylmercury neurotoxicity in the Faroe Islands. RESULTS: Adjustment for the benefits conferred by maternal fish intake during pregnancy resulted in an increased effect of the prenatal methylmercury exposure, as compared with the unadjusted results. The dietary questionnaire response is likely to be an imprecise proxy for the transfer of seafood nutrients to the fetus, and this imprecision may bias the confounder-adjusted mercury effect estimate. We explored the magnitude of this bias in sensitivity analysis assuming a range of error variances. At realistic imprecision levels, mercury-associated deficits increased by up to 2-fold when compared with the unadjusted effects. CONCLUSIONS: These results suggest that uncontrolled confounding from a beneficial parameter, and imprecision of this confounder, may cause substantial underestimation of the effects of a toxic exposure. The adverse effects of methylmercury exposure from fish and seafood are therefore likely to be underestimated by unadjusted results from observational studies, and the extent of this bias will be study dependent

Prenatal tobacco exposure is related to neurobehavioral modifications in infants of adolescent mothers

INTRODUCTION: Prenatal tobacco exposure interferes with neonatal outcomes. OBJECTIVE: To determine the neonatal neurobehavioral effects of in utero tobacco exposure. METHODS: This prospective cross-sectional study included healthy, term, with birth weight appropriate for gestacional age neonates without exposure to alcohol, drugs, or infections, born to adolescent mothers without psychiatric disorders or post-traumatic stress. Infants were classified according to in utero tobacco exposure, as identified by the Composite International Diagnostic Interview administered to mothers. Neurobehavior was assessed by the Neonatal Intensive Care Unit Network Neurobehavioral Scale. Both tools were administered between 24 and 72 hours after birth. Neurobehavioral outcomes were compared between exposed and nonexposed infants by ANOVA. The associations between neurobehavioral scores and number of cigarettes smoked were studied by linear correlation. RESULTS: During the study, 928 newborns of adolescent mothers were born, and 388 were included in the study. Of these, 23 were exposed to tobacco, and 365 neonates were not exposed. There were no differences between the groups in gestational age, birth weight, post-natal age at the exam, or time between last feeding and exam. Exposed neonates showed higher scores on arousal (p = 0.004), excitability (p = 0.003), and stress/abstinence signals (p = 0.019) and a lower score on regulation (p = 0.025). After adjusting for the type of anesthesia, mode of delivery, gender, age at neurologic exam, exam duration and time between last feeding and exam, differences in arousal and excitability remained significant. The mean number of cigarettes consumed daily was positively correlated with lethargy (p = 0.013) and inversely with attention (p = 0.043). CONCLUSIONS: Neonates exposed in utero to tobacco showed worse neurobehavioral performance between 24 and 48 hours of life