Fish, including both freshwater and saltwater fish and shellfish species, provide high quality protein and nutrients, including long chain omega-3 polyunsaturated fatty acids (docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA))^(1–3). DHA and EPA are important for fetal neural and retinal development and they may reduce inflammatory processes, increase vasodilation, reduce platelet aggregation, and influence the onset of labor through prostaglandin synthesis^(1,2,4). However, fish may also contain contaminants, such as methylmercury and persistent organic pollutants, which may adversely affect fetal development and impact pregnancy outcomes⁽⁵⁾.

Preterm and small for gestational age (SGA) infants are at increased risk of morbidity, mortality, and long term developmental deficits^(6,7). Growth restriction and preterm delivery can sometimes be attributed to known causes, such as medical conditions and gestation of multiples; however, the etiology remains unclear in many cases and novel approaches to prevention are needed. Recent studies^(8–15) suggest that consuming fish during pregnancy may increase birthweight and help to protect against preterm birth; however, concerns remain about the effects of contaminants found in fish on fetal health. These concerns are heightened by several recent studies that have reported associations between high consumption of specific types of fish and increased risk of preterm birth or SGA^(16–18).

Most of the studies that have assessed the associations between fish intake and pregnancy outcomes have been conducted in coastal European countries (Norway, Spain, France, and Denmark), where fish consumption habits are different than those in the United States (US)^{(9,10,13–17)}. Per capita fish consumption in Norway is twice as high as that of the US and inland farmed fish, including tilapia and catfish, make up a larger proportion of the domestic fish supply in the US than in Europe⁽¹⁹⁾. Prior US studies examining the relationships between fish consumption and birth outcomes have focused on specific populations: one was a clinical trial of women at high risk for preterm birth⁽¹¹⁾ and two were cohorts of predominantly non-Hispanic white women (66–88%) living in specific geographic regions (Boston and Washington State)^(18,20,21). Results from European studies and prior US studies may not generalize to the US population as a whole.

The objective of this study was to evaluate associations between fish consumption and preterm birth or SGA in a diverse sample of US women. To do so, we used data from the National Birth Defects Prevention Study (NBDPS), which surveyed a population-based sample of women as part of a case-control study of birth defects. Only control participants, who delivered an infant without a major structural birth defect, were included in the current analyses. To our knowledge, this is the largest US study to examine the relationship between maternal fish intake and preterm birth and SGA.

There were 11,829 control mothers included in the NBDPS with estimated due dates between 1997 and 2011 (version 10), and 11,451 (97%) women delivered singletons with a gestational age of at least 20 weeks and were eligible for inclusion in this study. Mothers missing fish consumption data (n=461) or with preexisting Type I or Type II diabetes (n=71) were excluded, leaving 10,919 mother-infant pairs for the preterm analysis. Infants were additionally excluded from the SGA analysis if they were missing birthweight (n=145), infant sex (n=10), or had a gestational age outside the gestational age range of 24 to 42 weeks (n=48). These exclusions left 10,716 mother-infant pairs for the SGA analysis. Overall, 853 (7.8%) infants were preterm and 828 (7.7%) were SGA, while 46 (0.4%) infants were both preterm and SGA.

Women reported 3.3 servings of fish per month on average and 31.6% (n=3,446) of women reported eating no fish or eating it less than once per month (Table 1). Maternal sociodemographic characteristics differed across fish consumption categories (chi-square p<0.05, Table 1). Women in the highest consumption group were more likely to be black, foreign born Hispanic, or foreign born other (self-reported race as Asian, Native American, or other), as compared to women in the lowest consumption group, who were more likely to be white or US-born Hispanic. Women in the highest and lowest consumption groups were more likely to have a high school education or less compared to women with moderate consumption (1–3 times per month, 1 time per week, or 2–6 times per week). Women who consumed fish 1–3 times per month, 1 time per week, or 2–6 times per week were more likely to have a college degree than women who consumed fish daily or less than once a month.

Our finding of an average of 3.3 servings (3–5 ounces) of fish per month is similar to other studies of US women that reported fish consumption of 3 to 3.5 ounces per week^(33,34). In this study, a higher proportion of women reported consuming fish less than once a month (31.6%) than European studies, where 8–18% of women reported no fish consumption^(8,9,16).

A recent meta-analysis that pooled data from 19 European birth cohorts found an 11–13% reduction in preterm birth among women eating fish twice a week or more compared to women eating fish once a week or less⁽¹²⁾. Studies that have categorized fish consumption in a similar manner to our study reported odds ratios for preterm birth of 0.84 for 2 times per week versus once a week or less⁽¹³⁾ and 0.65 for 2 times per week or more versus less than once a month⁽⁹⁾. While our association estimates of a 10–30% decrease in the odds of preterm birth among women eating fish twice a week or more were similar in magnitude to these European studies, our study lacked the precision needed to find an association of this magnitude. In contrast to most of the previous studies, one recent US study reported an increased risk of preterm birth among women consuming lean fish more than once per week^(18). We did not observe an increased risk of preterm birth among high consumers in our study, however, we were unable to evaluate lean fish consumption specifically.

Women reporting daily fish consumption had twice the odds of having an SGA infant compared to women who reported eating fish less than once a month; however, this estimate was based on 21 SGA infants and only a small proportion of women reported consumption levels this high. These findings should be replicated in future studies by included a high consumption category. Several prior studies have found an elevated risk of SGA among women consuming high levels of fatty fish⁽¹⁶⁾, shellfish (oysters, mussels, shrimp, prawns, lobster, and crab)⁽⁹⁾, crustaceans (a component of shellfish: shrimp, prawns, lobster, and crab)⁽¹⁷⁾, and canned tuna⁽¹⁷⁾. The adjusted odds ratio estimates for SGA among women consuming shellfish, crustaceans, and canned tuna twice a week or more were of similar magnitude to our findings (ORs 2.14, 2.45, and 2.49, respectively)^(9,17). As shellfish and canned tuna are among the most commonly eaten fish types in the US⁽³⁾, they may also have been the most commonly eaten types of fish among the women in our study who reported daily consumption of fish.

Evidence of a relationship between high maternal fish consumption and decreased birth weight has also been previously reported in the US. Mohanty et al. used a different outcome measure, low birth weight (<2500 g), and reported a 2.2-fold higher risk among women consuming lean fish more than once per week compared to non-consumers⁽²¹⁾. While we were unable to evaluate lean fish consumption specifically and replicate this finding in our study, lean fish, including canned light tuna, breaded fish products, and catfish, are also commonly eaten species in the US⁽³⁾.

Our study was limited by collecting fish consumption using a single question in the FFQ. A previous study demonstrated that a one-item FFQ about fish consumption correlated more closely with plasma DHA concentrations and comparably correlated with methylmercury intake compared to a four- or thirty-six-item FFQ⁽³⁵⁾. Longer FFQs were found to provide no advantage over one-item FFQs in ranking intakes of fish, DHA, and methylmercury⁽³⁵⁾. As in many previous studies, we were unable to assess which types of fish were consumed by women in the highest consumption group and how preparation methods may have impacted nutrient and contaminant contents. Since both fish and shellfish are sources of nutrients and possibly contaminants, more detailed consumption and preparation data should be collected in future studies. Additionally, since this was a secondary analysis of data from a study of birth defects in which the critical window for development of the outcome occurs early in pregnancy, this study queried average fish consumption during the year prior to conception. Prior studies of fish consumption and pregnancy outcomes vary widely in the timing of collection of fish consumption data, with studies collecting FFQ data in the first trimester^(9,18,21), second trimester^{(11,13,14,16)}, third trimester⁽⁸⁾, or at multiple points in pregnancy^(10,15,17). It is possible that some women in the present study may have changed their consumption habits during pregnancy. Recently Razzaghi & Tinker reported no differences in seafood consumption between pregnant and non-pregnant US women using both detailed 30-day fish intake data and 24-hour dietary recalls collected in the National Health and Nutrition Examination Survey from 1999 to 2006⁽³⁶⁾. Additionally, women were asked to recall their average consumption during the year prior to pregnancy, which may have introduced recall bias. Finally, there may be residual confounding or bias affecting our observed associations. Our calculated E-value of 3.6 indicates only a strong unmeasured confounder could fully explain the association observed between daily fish consumption and SGA. None of the potential confounders we did evaluate were associated this strongly with the outcome. While our results are fairly robust to unmeasured confounding and we assessed a number of potential confounders in our analyses, we cannot rule out the possibility that women who reported daily fish consumption may have had other co-occurring health behaviors or dietary patterns that were not assessed and may be driving the results.

The strengths of our study include the large sample size and the diverse study population from multiple regions across the US. We assessed the association between high fish consumption and SGA infants. Previous studies that have grouped fish consumption by quartiles may have masked elevated risk in high consumers by grouping them with moderate consumers. We would not have observed an association between high fish consumption and SGA if we had grouped women consuming fish 2 to 6 times per week with the highest consumers (1 or more times per day). Additionally, as our sample was based on NBDPS controls, none of the infants in our analyses had chromosomal abnormalities or other major structural birth defects, which can impact gestational age at birth and birth weight, and we were able to assess potential confounding by other dietary components calculated from the FFQ.

To the best of our knowledge, this is the first US study to observe an elevated risk of SGA among women reporting daily fish consumption. The elevated risk of SGA we observed among high fish consumers should be confirmed and future studies should collect more detailed data on fish consumption to investigate whether a specific component or contaminant is associated with SGA. Currently the US Food and Drug Administration (FDA) recommends that when eating fish from commercial sources, women of childbearing age and pregnant women should eat 2 to 3 servings of fish lower in methylmercury (“best choices”) or 1 serving of fish with moderate methylmercury content (“good choices”), while avoiding high mercury fish⁽³⁷⁾. Our results are consistent with the FDA recommendation in suggesting that, with respect to the risk of preterm birth and SGA, moderate intake of fish may be beneficial and high intake may be harmful. These results add to the body of evidence that women of childbearing age should be counseled on appropriate fish consumption for a healthy pregnancy.