The Seychelles Child Development Study is examining the association between fetal methylmercury exposure from a maternal diet high in fish and subsequent child development. The study is double blind and uses maternal hair mercury as the index of fetal exposure. An initial cross-sectional pilot study of 804 infants aged 1 to 25 months suggested that mercury may affect development. A follow up of 217 pilot children at 66 months of age also suggested that neurodevelopmental effects might be present, but the result was dependent on outcomes in a small number of children. On the basis of initial results in the pilot study a prospective, longitudinal main study with more covariates and expanded endpoints was begun on a new cohort of 779 children. No association with neurodevelopment was seen at 6 1/2, 19, or 29 months of age, but there was an inverse relationship at 29 months in boys only between mercury level and activity as judged by the examiner. Adverse neurodevelopmental effects from fetal mercury exposure in the pilot study are highly dependent on how the data are analyzed and no definite effects have been detected through 29 months of age in the main study. In a related study, 32 brains were obtained at autopsy from Seychellois infants. These were examined histologically and analyzed for mercury. No clear histological abnormalities were found. Mercury levels ranged from a background of about 50 ppb up to 300 ppb, and correlated well between brain regions. For 27 brains maternal hair from delivery was available and hair mercury correlated well with brain mercury.

Methylmercury (MeHg) is a human neurotoxin to which the developing fetal brain is especially sensitive. The lowest dose of MeHg that impairs neurodevelopment in the human fetus is not known. The Seychelles Child Development Study (SCDS) is testing the hypothesis that fetal MeHg exposure from a maternal diet high in oceanic fish is related to child neurodevelopmental outcomes. Fish is the major protein source in the Republic of Seychelles, where a cohort of 779 mother-infant pairs was enrolled in a prospective longitudinal study. Maternal total hair mercury values during pregnancy were determined by cold vapor atomic absorption and ranged from 0.5 ppm to 26.7 ppm with a median of 5.9 ppm. When the children were 6 1/2 months of age, an examiner blinded to the maternal mercury value performed a neurological examination, the Fagan test of visual recognition memory, and the Denver Developmental Screening Test-Revised (DDST-R). On the DDST-R 2% scored other than normal while 3.4% had an overall neurological score other than normal. The Fagan test of visual recognition memory showed a median score of 60.5%, and the Rose attention measure from that test showed a median score of 37.9. The association between fetal mercury exposure and neurodevelopmental endpoints was examined by multiple regression analyses. After adjusting for covariates, no association between the maternal hair mercury level during pregnancy and an adverse neurodevelopmental outcome of the child was identified at 6 1/2 months of age.

Despite the importance of defining developmental consequences for humans of in utero exposure to low levels of methylmercury, it is not yet clear if there are postnatal effects in fish-eating populations. The Seychelles Child Development Study (SCDS) now underway in the Republic of Seychelles, is following children to test the hypothesis that prenatal exposure to low concentrations of MeHg through maternal ingestion of fish is related to child development outcomes.In this study, children were evaluated with the Bayley Scales of Infant Development (BSID) at 19 mos. of age (N = 738). The cohort was evaluated again at 29 mos. (N = 736) with the BSID and the Bayley Infant Behavior Record. Mercury exposure determined by cold vapor atomic absorption analysis of maternal hair segments corresponding to pregnancy revealed a median exposure of 5.9 ppm (Range 0.5 - 26.7 ppm). The association between maternal hair mercury concentrations and neurodevelopmental outcomes at 19 and 29 mo. of age was examined by multiple regression analysis with adjustment for confounding variables. Results: BSID Intertester reliability was ascertained by the Kappa statistic and was high. The mean BSID Mental Sea le Indexes at both 19 and 29 mo. were comparable to the mean performance of US children. The mean BSID Psychomotor Scale Indexes at 19 and 29 mo. were 2 SD units above US norms, but consistent with previous findings of motoric precocity in children reared in African countries. No effect of mercury was detected on BSID scores at either age. On the Bayley Infant Behavior Record, activity level in boys, but not girls, decreased with increasing mercury exposure.Only one subjective endpoint was correlated with prenatal exposure to mercury. This study may have implications for environmental health policies concerning mercury in fish or fish consumption during pregnancy. Follow-up data are needed to determine if adverse effects occur at older ages and if such effects are determined to be related to mercury. (C) 1995 Intox Press, Inc.

The concentration of total mercury in maternal hair during pregnancy was used as a measure of fetal exposure to methylmercury in a study of a fish-eating population in the Seychelles islands. A segment of scalp hair approximately 10 centimeters in length, that grew during pregnancy, was selected for measurement. Total and inorganic mercury were measured by cold vapor atomic absorption (CVAA) using the Magos reagents (Magos, 1971). For comparative purposes, total mercury was measured by X-ray Fluorescent Spectrometry (XRF) and methylmercury by gas chromatography/atomic fluorescence detection (GC/AFD) in a subset of hair samples. A limited number of fish samples were also analyzed. Extensive interlaboratory testing was conducted to ensure accuracy of the mercury measurements. Concentrations of organic mercury calculated as the difference between total and inorganic mercury as measured by CVAA agreed with those of methylmercury measured on the same samples of hair by GC/AFD. Methylmercury measured by GC/AFD and organic mercury measured by CVAA accounted for over 80% of the total mercury in hair and over 90% of the total mercury in fish muscle. To test the accuracy of recapitulation by hair sampling, hair samples were collected from mothers at the time of delivery and 6 months later. The segment corresponding to the pregnancy term was selected for measurement assuming a hair growth rate of 1.1 cm/month. Results from both samples were in close agreement. As part of both a pilot investigation followed by the main study, maternal hair samples were collected each year from 1986 to 1989 for a total of 1604 samples. The median and mean values for each year's collection fell in the range of 5.9 to 8.2 ppm and exhibited no statistically significant trend with time. The highest recorded concentration was 36 ppm. In hair samples from 654 mothers, the mean concentration of total mercury was compared with the mean concentrations in segments corresponding to each trimester, approximately 3.3 centimeters in length. A high degree of correlation was found between mean levels in each trimester versus the entire pregnancy segment.

Studies in Japan showed that fetal exposure to methylmercury during pregnancy can lead to severe neurodevelopmental changes in the infant while the mother suffers no or minimal effects. Fish contains methylmercury and there is concern that adverse neurodevelopmental effects may occur secondary to low-dose methylmercury exposure in utero from maternal fish consumption. The Seychelles Child Development Study has been examining the relationship between prenatal exposure to methylmercury during pregnancy in a population with high fish consumption and the neurodevelopmental outcome. Over 80% of Seychellois women eat fish daily, and the median fish meals per week during pregnancy is 12. Following a pilot study of 804 mother-infant pairs, a longitudinal main study of another 779 mother-infant pairs was initiated. The main study design includes collection of educational and socioeconomic information about the family and periodic standardized neurodevelopmental tests at specific ages from 6 1/2 months to 66 months of age. In this paper, we describe the background to the studies and give demographic characteristics of both the pilot and main study cohorts.

Maternal consumption during pregnancy of methylmercury (MeHg)-contaminated fish in Japan and of MeHg-contaminated bread in Iraq caused psychomotor retardation in the offspring. Studies in Iraq suggested adverse fetal effects when maternal hair mercury concentrations were as low as 20 ppm. This prospective study involved 131 infant-mother pairs in Mancora, Peru with peak maternal hair MeHg levels during pregnancy from 1.2 ppm to 30.0 ppm, geometric mean 8.3. The MeHg was believed to be derived from marine fish in the diet. There was no increase in the frequency of neurodevelopmental abnormalities in early childhood. The possible role of selenium or other protective mechanisms in marine fish is discussed. This previously unpublished study was conducted between 1981 and 1984. Our report of August 1985 to the funding agencies has been circulated, and the data were presented at the Twelfth International Neurotoxicology Conference in Hot Spring, Arkansas, October 30 to November 2, 1994. The current account has not been modified or updated since 1985. For reference to interim publications on fetal MeHg studies in Iraq and New Zealand see Marsh et al., 1995.

The Seychelles Child Development Study (SCDS) is testing the hypothesis that prenatal exposure to low concentrations of methylmercury from a maternal diet high in fish is related to the child's developmental outcome. In this report, 217 children from a pilot cohort were reevaluated at 66 months of age. The evaluation included the McCarthy Scales of Children's Abilities, the Preschool Language Scale, and age-appropriate sub-tests from the Woodcock-Johnson Tests of Achievement. Maternal hair total mercury, measured by cold vapor atomic absorption in a maternal hair segment corresponding to pregnancy, revealed a median exposure of 7.1 ppm. The association between maternal hair mercury levels and neurodevelopmental outcomes at 66 months of age was examined by multiple linear regression analysis with adjustment for important confounding variables. The results indicated that mercury exposure was negatively associated with four endpoints (the McCarthy General Cognitive Index and Perceptual Performance subscale and The Preschool Language Scale Total Language and Auditory Comprehension subscale). After normalizing the data by removal of a small number of outliers or highly influential scores, the mercury effects were no longer significant except for auditory comprehension. These results should be viewed as preliminary and interpreted with caution, since the SCDS main study 66-month evaluations, which are better controlled with more detailed endpoints are being analyzed. This study highlights the difficulties in interpreting epidemiologic studies of this type and the degree to which overall results in multivariate analyses can be influenced by a very small number of cases.

Autopsy brains were obtained from infants dying from a variety of causes within a few days of birth in a population exposed to methylmercury in fish. Infant and maternal blood and hair samples were also obtained. The concentration of total mercury in 6 major brain regions were highly correlated with maternal hair levels. This correlation was confirmed by a sequence of comparisons of maternal hair to maternal blood to infant blood and finally to infant brain. The results lend support to the use of maternal hair in assessing fetal exposure to methylmercury in fish-eating populations.

The Seychelles Child Development Study was designed to provide data on normal neurodevelopment of Seychellois children and to examine the relationship of their neurodevelopmental outcomes to in utero fetal exposure to low concentrations of methylmercury from a maternal diet high in fish. This paper outlines the strategies used to select, modify, and field test evaluation tools used in the main longitudinal prospective study of 740 children (95% of the cohort of 779 initially enrolled in 1989). It also gives population statistics and quality assurance data for the tests administered and the evaluation of the home environments.

Mononeuritis multiplex is known to occur in many illnesses including certain types of systemic vasculitis. Anti-neutrophil cytoplasmic autoantibody (ANCA) has been described in association with Wegener's granulomatosis, polyarteritis nodosa, pauci-immune necrotizing crescentic glomerulonephritis, and so-called ANCA-associated vasculitis. We describe three patients who presented with mononeuritis multiplex and positive tests for ANCA. A careful search revealed underlying vasculitis in two of the three patients. Whereas both respiratory and renal involvement are well known in ANCA-associated vasculitis, to our knowledge the relationship of mononeuritis multiplex and ANCA positivity has not previously been described. The three patients were treated with steroids and oral cyclophosphamide. All demonstrated marked clinical improvement, as well as a decrease or disappearance of the ANCA. Since mononeuritis multiplex may be a presenting symptom of many illnesses, a serological marker may be helpful for early diagnosis and prompt treatment.

A new method of estimating fetal exposure is used in a dose-response analysis of data from the 1971 outbreak of methyl mercury poisoning in rural Iraq. An X-ray fluorescence instrument for the measurement of single strands of human hair was employed to obtain longitudinal profiles recapitulating fetal exposure. Logit and hockey-stick models as well as nonparametric smoothing are used to describe data on delayed development and central nervous system abnormality.

Eighty-four Iraqi mothers and their infants had been exposed to methylmercury during pregnancy. The methylmercury had been ingested as a fungicide. Peak maternal hair mercury concentrations were related to the frequency of maternal symptoms during pregnancy and to neurological effects in the infants. These include various degrees of psychomotor retardation. Severe neurological deficits were observed in five children whose maternal peak hair mercury concentrations were 165 to 320 ppm. Minimal symptoms were reported for mothers and children when peak maternal hair levels were below 68 ppm. Minimal clinical neurological signs occurred in children when peak maternal hair mercury concentrations were at an undetermined point between 68 and 180 ppm. Greater fetal risk appears to be associated with exposure during the second trimester. This exposure to methylmercury was acute and the results may not be extrapolated to a constant level of exposure throughout pregnancy. The effects of fetal exposure to methylmercury in marine fish may differ.

This report describes psychomotor retardation in infants caused by prenatal exposure to methylmercury. A study of 29 mother‐infant pairs established a relationship between maximum maternal hair mercury concentration during pregnancy and the frequency of neurological effects in the infants. The latter included delayed achievement of developmental milestones with or without neurological signs. The infants were 4 1/2 to 5 years of age on last examination. Ten infants of mothers who had maximum hair concentrations in the range of 99 to 384 parts per million (ppm) had a significantly higher frequency of abnormal findings than those in two groups having lower maternal hair mercury concentrations (12 to 85 and 0 to 11 ppm). The group sizes were too small to allow identification of a specific ‘threshold’ maternal hair concentration above which such effects can be expected. Transient paresthesias during pregnancy occurred in 80% of the mothers in the higher concentration group (99 to 384 ppm) as compared with 30% and 22% in the lower groups. Neurological abnormalities were found in some children whose mothers had been asymptomatic during pregnancy.

A Peruvian population was identified that was chronically exposed to methylmercury from the long-term consumption of ocean fish. The weekly fish intake averaged 10.1 kg per average family of 6.2 persons. Blood methylmercury concentrations ranged from 11 to 275 ng/ml, with a mean of 82 ng/ml. Paresthesias were reported by 29.5% of the population. In contrast, a nearby control population had a mean weekly fish consumption of 1.9 kg per average family of 6.4 persons. Their blood methylmercury levels were 3.3-25.1 ng/ml, with a mean of 9.9 ng/ml. Paresthesias were reported by 49.5% of this control group. No individual was identified with symptoms or signs that could be attributed to methylmercury intoxication.