Fish and seafood are regarded healthy components of a varied diet, particularly important for pregnant women so that they can pass on essential nutrients needed for fetal development of the brain and other organs1. On the other hand, fish may contain environmental pollutants, such as methylmercury, that can put fetal brain development at risk2. A balance has been sought by state and federal agencies in advising the public 3, but certain subpopulations (i.e. pregnant women or women of childbearing age) generally eat less fish than desirable in order to obtain the beneficial effects of fish 1. At the same time, U.S.EPA reports that over 300,000 children born every year exceed the Reference Dose (RfD) for methylmercury and may therefore be at risk at developing adverse effects4.

Tragic pollution episodes have clearly documented that the fetal brain is particularly susceptible to methylmercury toxicity; the adverse effects on the nervous system appear to be irreversible and are much more widespread and serious in children than in adults, especially when exposures have occurred prenatally5,6. While the existence of adverse effects at low exposure levels has been affirmed by national and international regulatory agencies,7-10 certain scientific questions remain unanswered. They relate to the possible occurrence of neurotoxic effects close to the U.S.EPA Reference Dose, the persistence of the cognitive deficits through adolescence, and the possible compensation of adverse effects by essential nutrients present in fish and seafood. The proposed research aims at developing new and more definite information on the benefits and risks associated with seafood intakes at levels relevant to the US general population.

This proposal builds upon the extensive data already collected on a cohort of 14,138 children born between April 1st 1991 and December 31st 1992 in Avon, England, as part of the Avon Longitudinal Study of Parents and Children (ALSPAC) study11. The focus was to identify features of the environment that affect the health and development of children. Detailed information and biological samples were collected at the time of birth and continue to be collected during the course of follow-up11. A10% sample randomly selected was seen at 4, 8 and every 6 months until age 5 years with data including motor and intellectual development. From age 7 years, all children were invited annually for neurobehavioral assessment (including IQ). A pilot project was carried out to measure cord-mercury wet-weight concentrations12, and frozen cords are available from 7,500 subjects to link to the outcome parameters already available.

Because cord tissue has been collected from over half of the children, and because the mercury concentration in the umbilical cord is an excellent biomarker of prenatal exposure levels13, the opportunity exists to assess the developmental mercury exposure level to determine its possible impact on highly relevant neurodevelopmental functions, and the possible interaction with beneficial effects of maternal fish intake.

The specific aims of this project are therefore: to determine if methylmercury-associated cognitive deficits are present at low-level prenatal methylmercury exposures and remain detectable through to adolescence;

• to examine whether intake of fish containing beneficial nutrients affect the same outcomes and counterbalance the methylmercury-associated deficits; and
• to identify other behavioral outcomes that are linked to prenatal methylmercury exposure for possible consideration in future research.