A Quantitative Analysis of Prenatal Intake of n-3 Polyunsaturated Fatty Acids and Cognitive Development

Abstract

Although a rich source of n-3 polyunsaturated fatty acids (PUFAs) that may confer multiple health benefits, some fish also contain methyl mercury (MeHg), which may harm the developing fetus. U.S. government recommendations for women of childbearing age are to modify consumption of high-MeHg fish to reduce MeHg exposure, while recommendations encourage fish consumption among the general population because of the nutritional benefits. The Harvard Center for Risk Analysis convened an expert panel (see acknowledgments) to quantify the net impact of resulting hypothetical changes in fish consumption across the population. This paper estimates the impact of prenatal n-3 intake on cognitive development. Other papers quantify the negative impact of prenatal exposure to MeHg on cognitive development, and the extent to which fish consumption protects against coronary heart disease mortality and stroke in adults.

This paper aggregates eight randomized controlled trials (RCTs) comparing cognitive development in controls and in children who had received n-3 PUFA supplementation (seven studies of formula supplementation and one study of maternal dietary supplementation). Our analysis assigns study weights accounting for statistical precision, relevance of three endpoint domains (general intelligence, verbal ability, and motor skills) to prediction of IQ, and age at evaluation. The study estimates that increasing maternal docosahexaenoic acid (DHA) intake by 100 mg/day increases child IQ by 0.13 points. The paper notes that findings were inconsistent across the RCTs evaluated (although our findings were relatively robust to changes in the weighting scheme used). Also, for seven of the eight studies reviewed, effects are extrapolated from formula supplementation to maternal dietary intake.

Introduction

Because of evidence that prenatal exposure to methyl mercury (MeHg) in fish may adversely affect cognitive development, the U.S. Food and Drug Administration (FDA) and the U.S. Environmental Protection Agency issued a joint advisory in March 2004 recommending that pregnant women modify their fish consumption.¹ However, fish is a rich source of n-3 polyunsaturated fatty acids (PUFAs). The n-3 PUFAs may confer protection against coronary heart disease (CHD) and stroke in adults, and may benefit cognitive development of the fetus during pregnancy.

Depending on how they are implemented, interventions to decrease exposure to MeHg may decrease overall fish consumption. For example, Oken et al.² reported a 17% decrease in fish consumption among pregnant women following the release of the FDA’s 2001 MeHg advisory. Moreover, other members of the population could decrease their fish consumption as an unintended consequence of risk management actions targeting MeHg exposure among women of childbearing age.

In order to understand the possible public health ramifications of alternative risk management actions, it is necessary to quantify potential health benefits and risks associated with plausible changes in population fish-consumption patterns. This paper reviews the literature on the cognitive benefits of increasing n-3 intake in infants as a starting point for quantifying the benefits of maternal n-3 intake during pregnancy, since there is limited direct information on the relationship between maternal n-3 intake during pregnancy and cognitive development of the fetus. These benefits can then be compared to the risks associated with mercury exposure associated with fish consumption. This paper quantifies the cognitive benefits of n-3 consumption in terms of changes in cognitive ability as measured by IQ. In particular, this analysis quantifies the permanent change in child IQ score per gram per day increase in maternal n-3 PUFA intake. Developing this estimate involves the aggregation of results across studies using different test instruments, extrapolation of impacts from early in childhood to later in life, and extrapolation of findings from studies investigating supplementation of baby formula with n-3 PUFAs to maternal intake of n-3 PUFAs during pregnancy.

Three other papers in this issue of the American Journal of Preventive Medicine develop dose–response relationships between prenatal MeHg exposure and IQ, and between adult fish consumption and both stroke incidence and CHD mortality.3, 4, 5 A fifth paper, also in this issue, combines these results to estimate the aggregate health effects of hypothetical changes in fish consumption on public health.⁶

There have been at least two efforts to systematically review the literature on cognitive function and infant intake of n-3 PUFAs.7, 8 However, those reviews are not sufficient for our purposes for two reasons. First, although they summarize the findings of different studies, these reviews do not quantitatively aggregate the findings so that they can be expressed in terms of a common metric (IQ points gained per gram per day of n-3 PUFA intake). Second, these reviews do not consider several recent studies that were not available at the time of their publication.

The remainder of this paper has three parts. The next section describes the methodology for aggregating information across studies that have measured this effect to quantify this relationship. The Results section reports the results in terms of the change in IQ associated with supplement intake. Finally, the findings are discussed and the dose–response relationship between IQ and maternal n-3 PUFA intake (IQ points per gram per day of n-3 maternal intake) is quantified.