a Institute of Public Health, University of Southern Denmark, DK-5000 Odense, Denmark.
b Departments of Environmental Health and Neurology, Boston University Schools of Medicine and Public Health, Boston, MA 021182526, USA.
c Department of Clinical Chemistry, Trondheim University Hospital, N-7000 Trondheim, Norway.
d Faroese Hospital System, FO-100 Tórshavn, Faroe Islands.
Prof. Philippe Grandjean, University of Southern Denmark, Winslowparken 17, 5000 Odense, Denmark. E-mail: pgrandjean{at}health.sdu.dk
Abstract
Background Marine food provides essential fatty acids that are important during pregnancy, but the benefits may be limited at high intakes and by seafood contaminants.
Methods In the fishing community of the Faroe Islands, 182 pregnant women with spontaneous singleton births were consecutively recruited for a cohort in 1994 1995. Concentrations of fatty acids and seafood contaminants in blood samples were analysed as predictors of gestational length and birthweight.
Results Serum concentrations of eicosapentaenoic acid (EPA) increased with maternal marine food intake, while the tendency was less clear for docosahexaenoic acid (DHA). An increase in the relative concentration of DHA in cord serum phospholipids by 1% was associated with an increased duration of gestation by 1.5 days (95% CI : 0.72.2). However, birthweight adjusted for gestational length decreased by 246 g (95% CI : 16476) for each increase by 1% of the EPA concentration in cord serum. Concentrations of the seafood pollutants mercury and polychlorinated biphenyls (PCB) were associated with fatty acids levels, but the contaminants did not appear to affect any of the outcome parameters.
Conclusion An increased intake of marine fats appears to prolong the duration of gestation, but birthweight adjusted for gestational age may decrease at high intake levels. This effect does not seem to be due to increased exposures to seafood contaminants.
Keywords Birthweight, eicosapentaenoic acid, diet, docosahexaenoic acid, fish oil, gestational age, n-3 polyunsaturated fatty acids, pregnancy
Accepted 6 February 2001
Seafood contains n-3 polyunsaturated fatty acids (PUFA), mainly eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3),1,2 that have important functions during gestation. Thus, a randomized controlled trial using a small daily supplement of 2.7 g fish oil during pregnancy showed prolonged gestation and increased birthweight.3 In the fishing community of the Faroe Islands, a similar overall tendency was also observed, but birthweight and placenta weight decreased at the highest frequencies of seafood dinners.4 The latter observation is supported by experimental evidence in rats where high doses of fish oil caused a decreased birthweight despite an increased gestational length.5,6 Seafood and fish oil may also contain toxic contaminants, including polychlorinated biphenyls (PCB),7 that have been associated with decreased birthweight810 and decreased birth length in boys,11 although no effect was encountered in other studies.12,13 Methylmercury, another seafood contaminant, has been linked with lower birthweights in Greenland populations,14 while Cree Indian15 and Faroese16 birthweights showed an increase at higher maternal exposures to mercury.
The health implications of a maternal seafood diet during pregnancy are likely to represent a balance between beneficial effects of essential nutrients and adverse effects caused by toxicants or by possible oversupplies of nutrients.17 However, studies of essential fatty acids did not consider the potential toxicity due to contaminants, and vice versa. Thus, current evidence does not allow an evaluation of the relative importance of and possible interactions between these seafood components.
We have therefore examined these issues in a birth cohort from the Faroe Islands, a community of 42 000 inhabitants located between Shetland and Iceland. In addition to large-scale fishing, the Faroese conduct occasional subsistence whaling which provides pilot whale meat and blubber for local distribution. In this homogeneous community, dietary habits depend on local availability and personal preferences, rather than socioeconomic factors. A questionnaire study of Faroese adults showed an average daily consumption of 72 g fish, 12 g whale muscle and 7 g of blubber, with fish and pilot whale meat constituting 44% and 9.5% of dinner meals, respectively.18 While the concentration of essential fatty acids may be lower in whale blubber than in fish oil, PCB concentrations in blubber average up to 30 µg/g.19 The lean whale muscle contains mercury concentrations at about 2 µg/g.20 Fish is an important dietary source also of selenium1 which may offer some protection against mercury toxicity.17 Given the occurrence of high exposures to both beneficial and potentially toxic components of marine food, this population would seem useful for examining the implications of a seafood diet for pregnancy outcome.
Subjects and Methods
Study population
A cohort of 182 singleton term births was generated from consecutive spontaneous births during a 12-month period in 19941995 at the National Hospital in Tórshavn.21 To obtain the widest possible range of contaminant exposures, the cohort was based on the primary catchment area away from the capital area of Tórshavn, i.e. the central and northwestern villages where access to fish and whale is the easiest. This cohort represents 64% of the 293 births occurring during this period; only few women did not consent to participate, and incomplete sampling was mainly due to surgical intervention or logistic problems in the busy ward. In addition, four children were excluded because of birth before the 36th week of gestation, and two children because they had congenital neurological disease. Low birthweight was not used as an exclusion criterion, but none was below 2500 g. Taking into account the exclusions, the overall participation rate is only slightly below the one obtained in a previous Faroese cohort.16
Obstetric and nutritional data
Relevant obstetric data were obtained by standardized procedures. Estimated gestational length took into account day of last menstruation, ultrasound examination conducted approximately at week 22 of pregnancy, and clinical impression; disagreements were resolved by the Dubowitz score.22 Birthweight and placental weight were measured by the midwife. Two weeks after parturition, a brief nutrition questionnaire comparable to the previous study4,23 was administered to all mothers to record frequencies of main meals with fish (number per week), whale meat, and whale blubber (both as number per month) during pregnancy (Table 1). Information on fish species or portion sizes was not obtained.
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Both maternal serum and cord serum were analysed for phospholipid fatty acids.24,25 A human control serum stored at 80°C was used to monitor analytical performance, and dayto-day precision for each fatty acid was generally within 5% (coefficient of variation). Results were computed as relative weight per cent for essential n-3 PUFA from fish oil (EPA and DHA), arachidonic acid (AA, 20:4n-6) as an essential n-6 PUFA, and the most relevant elongation and desaturation products, i.e. eicosatrienoic acid (ETA, 20:3n-9), docosatetraenoic acid (DTA, 22:4n-6) and docosapentaenoic acid (DPA, 22:5n-6).
Maternal serum was analysed for persistent organochlorine contaminants, including 28 PCB congeners.21,26 When expressed in relation to the serum lipid concentration, PCB concentrations are similar in maternal and cord serum.21 Because of collinearity between the lipophilic contaminants, PCB was calculated as the sum of all detectable PCB congeners and was used as indicator of long-term exposure to persistent organochlorine compounds.
Whole blood from the cord was analysed for mercury27,28 and selenium.29
Statistical analyses
Contaminant concentrations were logarithmically transformed because of skewed distributions. Parametric methods were applied throughout, except when questionnaire data required the use of Spearman's correlation coefficient (rs). Multiple regression analysis was used to determine the relative importance of relevant predictors of the outcome parameters. Potential confounders were identified on the basis of previous studies16,30 and included maternal height, maternal weight, smoking during pregnancy, diabetes, parity, gestational length, and sex of the child. Covariates were kept in the final regression equation if statistically significant (P < 0.1) after backward elimination.
Results
Half of the women reported that they had fish for dinner at least three times per week during pregnancy; about 60% had whale meat, and slightly more than one-half had whale blubber, for dinner at least once per month (Table 1). Most women (147; 82.6%) had not changed their dietary habits in this regard during the pregnancy. Average birthweight was high (Table 2
), with only 12 (6.6%) being below 3000 g.
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Table 4 shows associations of fatty acid concentrations in cord serum with indicators of a maternal diet rich in marine fats. The EPA increased at high intake levels, while ETA, DTA and DPA decreased. Similar, though less marked, tendencies were observed for maternal serum concentrations. The PCB concentration showed much the same associations with the PUFA concentrations, except that it showed a negative association with AA (Table 4
). Mercury showed similar, though weaker associations in the same direction.
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For birthweight, the significant covariates were gestational length, parity, maternal height, smoking, and gender of child. Birthweight showed a positive correlation with cord serum concentrations of ETA and DPA and a negative association with EPA (Figure 1). An increase in the relative EPA concentration in phospholipids by 1% was associated with a decrease in birthweight by 246 g (95% CI : 16476). Birthweight also seemed to decline slightly at increased PCB concentrations. This parameter was therefore added to the full regression model along with the EPA concentration as the most relevant fatty acid (Table 6
). Although the tendency for increased PCB remained, it was far from significant and much less important than EPA and the known predictors of birthweight.
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Maternal serum PUFA concentrations showed weaker associations in the same directions as seen with the cord serum concentrations. However, selenium concentrations showed no clear associations with the obstetric outcomes, and the same applied to the dietary questionnaire results concerning seafood dinner frequencies.
Discussion
The Faroese averages for n-3 PUFA concentrations in serum are higher than most previously published values.3137 For example, the average concentration of DHA in Faroese cord serum is about twice as high as comparable data from the Netherlands.36,37 These increases in serum concentrations of the n-3 PUFA were associated with seafood intake, and concurrent decreases were seen in desaturation levels, as indicated by ETA, DTA and DPA. The associations observed are in agreement with previous results from Norway using the same analytical method.32,33 While no effect of seafood diets on AA would be expected,3234 a significant decrease in AA concentrations at high PCB levels deserves attention in future studies.
Fatty acid concentrations in serum are a result of a dynamic interaction between absorption, degradation and, for some of them, catabolism, as well as changes in transplacental passage.31,38 The fact that concentrations of individual fatty acids correlated well in the paired samples and that maternal dietary habits were reflected in cord serum concentrations is in agreement with the passage of PUFA across the placental barrier.39 Although some PUFA showed a relative accumulation on the fetal side, the cord serum concentrations were much below maternal levels. These results corroborate previous findings at lower concentrations.3438
Cord serum concentrations showed clearer associations with the outcome variables than did maternal levels. Although the maternal serum samples were obtained at a standardized time, the cord serum concentrations at birth may more accurately reflect the availability of PUFA to the fetus. Physiological changes during pregnancy and the time interval between collection of the paired samples must be taken into account, but PUFA concentrations in cord serum seem to change only little during the last few weeks of normal gestation.36,38
The results obtained support the notion that increased intakes of DHA may prolong gestation, as documented in a randomized controlled trial in a population with low seafood intakes.40 However, erythrocyte concentrations of n-3 PUFA were found to be associated with gestational length only at low average seafood consumption and not in a high-intake group of Faroese women.41 Thus, the major benefit of n-3 supplements may occur within the low range of intakes.
The fatty acids that prolong the gestational period may not necessarily augment fetal growth. The high average birthweight in the present study is similar to previously reported results.4,16 However, at increasing levels of seafood intake, birthweight first seemed to increase and then to diminish.4 In the present study, birthweight showed a negative correlation with EPA concentrations. Likewise, higher levels of desaturation products were associated with both lower birthweight and higher placental weight. While increases in concentrations of desaturation products occur when supplies of essential fatty acids are insufficient,42 the concentrations seen in this study are much below those reported from other locations.3537 These findings therefore suggest that both essential fatty acid intake and desaturation activity affect the degree of relative sufficiency or excess, and that they could conceivably affect fetal growth even within serum concentration ranges otherwise considered optimal.
Experimental evidence also suggests that a high intake of n-3 PUFA may cause decreased intrauterine growth.5,6 Although the mechanism is unknown, excess prenatal exposure to PUFA may well lead to augmented lipid peroxidation,43 which may be particularly harmful during development.44 However, antioxidant selenium also occurs in seafood45 and could potentially counter this possible risk at high seafood intakes. Serum selenium concentrations increase with the duration of the pregnancy,23,46 but this element showed no clear association with gestational length or birthweight in the present study.
While the findings of the present study are in agreement with a fish-oil induced prolongation of gestation, the possible stresses induced by excess intakes therefore deserve attention. Fish oil supplements during pregnancy may be indicated only for prolongation of the gestational period when n-3 PUFA status is low.
Seafood contaminants also deserve consideration, although the major concern may relate to neurotoxicity,9,21 rather than intrauterine growth retardation. The increased concentrations of PCB and mercury in the present study are comparable to previously published levels from the Faroes,23,28,47 but the average PCB concentration is about threefold higher than in the Netherlands.9,21 The mercury average is similar to results from Greenland14 but about one order of magnitude higher than those reported from populations not relying on seafood.29 However, despite previous reports on possible adverse effects on birthweight,811,14 the present study of a wide exposure interval provides no evidence of an exposure-associated decrease in birthweight. While a small effect could possibly be hidden by the much greater impact of the associated n-3 PUFA, increased contaminant exposure seems not to be the explanation of the decrease in birthweight associated with high EPA concentrations.
Conclusion
The duration of gestation is prolonged at increased intakes of marine lipids and associated serum concentrations of PUFA. However, birthweight adjusted for gestational age may decrease at high intake levels. This effect is apparently not due to seafood contaminants. After adjustment for PUFA and other covariates, mercury and PCB were poorly associated with birthweight.
KEY MESSAGES
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Addendum
Longnecker et al. have just reported an increased risk of preterm birth and decreased birthweight at increased maternal serum concentrations of p,p-DDE (median, 25 µg/l; range, 3178 µg/l) in a US birth cohort from 19591966. No information is given on PCB concentrations. In our cohort, concentrations of DDE and PCB were highly correlated (r = 0.85), and the DDE concentrations were lower (median, 6 µg/l; range, 1.550 µg/l) than in the US study. The DDE concentration on a volume basis as well as lipid-adjusted was poorly related to gestational age, birthweight and placental weight. In a multiple regression analysis similar to the one shown in Table 6, beta for the logarithmic transformation of the volume based DDE concentration was 135 (p = 0.20).
Reference
1 Longnecker MP, Klebanoff MA, Zhiou H, Brock JW. Association between maternal serum concentration of the DDT metabolite DDE and preterm and small-for-gestational-age babies at birth. Lancet 2001;358:11014[ISI][Medline]
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This study was supported by grants from the European Commission (Environment and Climate Research Programme, EV 5V-CT940 472), the US National Institute of Environmental Health Sciences (ES06894), and the Danish Medical Research Council. We are indebted to members of the Faroese health care system for assistance in generating this cohort and in conducting the examinations of the children and to Brita Andersen and Sylvia Nome Kvam for laboratory assistance. Drs PJ Jørgensen and JW Brock made results available on mercury and organochlorine concentrations, respectively. The cohort was generated as part of the European study on Neonatal PCB-Exposure and Neurodevelopmental Deficit coordinated by Dr G Winneke, Düsseldorf, Germany.
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