Maternal Fish Intake in Late Pregnancy and the Frequency of Low Birth

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486 J Epidemiol Community Health: first published as 10.1136/jech.2003.013565 on 13 May 2004. Downloaded from RESEARCH REPORT Maternal fish intake in late pregnancy and the frequency of low birth weight and intrauterine growth retardation in a cohort of British infants I Rogers, P Emmett, A Ness, J Golding, ALSPAC Study Team ......

J Epidemiol Community Health 2004;58:486–492. doi: 10.1136/jech.2003.013565

Objective: To investigate the relation between maternal fish intake in late pregnancy and the frequency of low birth weight and intrauterine growth retardation (IUGR). Participants: 11 585 pregnant women in south west England. Methods: Information on fish intake was obtained from a food frequency questionnaire sent to the women at 32 weeks’ gestation, and used to calculate n-3 fatty acid (n-3FA) intake from fish. IUGR was defined as See end of article for authors’ affiliations a birth weight for gestational age and sex below the 10th centile. Confounding variables considered ...... included maternal age, height, weight, education, parity, smoking and drinking in pregnancy, and whether the mother was living with a partner. Only singleton, liveborn infants were included. Correspondence to: Dr I Rogers, Unit of Main results: Mean daily intakes of fish and n-3FAs were 32.8 g and 0.147 g respectively. In unadjusted Paediatric and Perinatal analyses there were positive associations between mean birth weight and fish intake or n-3FA intake, but Epidemiology, Department these disappeared on adjustment for potential confounders. The frequency of IUGR decreased with of Child Health, University increasing fish intake—the OR (95%CI) of IUGR in those eating no fish was 1.85 (1.44 to 2.38) compared of Bristol, 24 Tyndall Avenue, Bristol BS8 1TQ, with those in the highest fish intake group. On adjustment this relation was attenuated (adjusted OR 1.37 UK; Imogen.Rogers@ (1.02 to 1.84)), but the decline in the frequency of IUGR with increasing fish intake remained statistically bristol.ac.uk significant. No relation was observed between mean gestation and fish or n-3FA intake. Accepted for publication Conclusions: These results lend some support to the hypothesis that raising fish or n3-FA intake during 17 October 2003 pregnancy may increase fetal growth rate. However, they provide no evidence that increasing fish ...... consumption is associated with an increase in mean gestation. copyright.

here is some evidence that birth weight and length of The effect of fish oil supplementation on pregnancy gestation are increased among communities with a high outcome has been examined in two normal populations of habitual intake of fish such as the Faroe and Orkney pregnant women. In one trial 533 healthy pregnant women T 12 Islands. This has been attributed to the n-3 fatty acid were assigned to receive either 2.7 g fish oil, 2.7 g olive oil, or (n-3FA) content of marine foods. It has been suggested that no supplement daily from 30 weeks of pregnancy.10 Average n-3FAs may increase fetal growth rate by increasing the ratio duration of gestation and birth weight were greatest in the of biologically active prostacyclins to thromboxanes, reduc- fish oil group, although there were no differences between ing blood viscosity, and thereby facilitating placental blood the groups in birth weight for gestational age. The other http://jech.bmj.com/ flow. Alternatively they may prolong gestation by inhibit- trial of normal pregnant women took place in London during ing the production34of the prostaglandins that seem to play the 1930s.11 A supplement containing vitamins, minerals, and a part in parturition, cervical ripening, and initiation of 0.36 g halibut liver oil significantly reduced the frequency labour.5 of preterm births. The lack of success of similar vitamin Four observational studies in Denmark and the Faroe and mineral supplements in preventing preterm birth Islands have related fish intake to pregnancy outcome and suggests that the fish oil component may have been obtained mixed results.6–9 Two found fish consumption to responsible.12 on September 26, 2021 by guest. Protected be positively associated with birth weight but not with Two supplementation trials have been conducted on gestational age—the largest assessed fish consumption in women with high risk pregnancies (high risk of pregnancy 11 980 Danish women by questionnaire at 36 weeks gesta- hypertension, preterm delivery, or intrauterine growth tion6 and the other assessed fish intake by an interview retardation (IUGR)). One of these assigned 233 women to after delivery in 1362 women in the Faroe Islands.7 A third either 2.7 g daily fish oil or placebo and found no difference study assessed fish intake in mid gestation in 965 Danish in mean gestation, birth weight, or frequency of IUGR.13 The women,8 and found no relation with birth weight or gestation other supplemented 63 women with either 3 g of eicosapen- in an analysis adjusted for maternal size, parity, and taenoic acid (EPA) or a coconut oil placebo and found no smoking. Erythrocyte measures of n-3FA status were also difference between the supplement groups in the recurrence unassociated with birth outcome. The fourth related seafood rate of IUGR, in fact birth weight centiles were slightly lower intake assessed in early pregnancy (16 weeks’ gestation) to in the EPA group.14 This is in line with the results of studies pregnancy outcome.9 Fish intake was strongly negatively on rats, where administering fish oil in pregnancy consis- associated with the risk of both low birth weight (LBW) and tently results in reduced birth weight.15–17 preterm delivery—after controlling for multiple confounders the ORs for LBW and preterm delivery were 3.22 and 2.69 respectively in those eating no fish compared with the Abbreviations: LBW, low birth weight; IUGR, intrauterine growth highest fish intake category. retardation; EPA, eicosapentaenoic acid; n-3FA, n-3 fatty acid

www.jech.com Fish intake in pregnancy and birth weight 487 J Epidemiol Community Health: first published as 10.1136/jech.2003.013565 on 13 May 2004. Downloaded from

Table 1 Frequency of consumption of white fish, oily fish, and shellfish by 11 511 women during the third trimester of pregnancy. Values are percentages (n)

Never or rarely Once in 2 weeks 1–3 times per week 4–7 times per week .Once a day

White fish* 18.4 (2131) 40.2 (4659) 40.0 (4632) 1.4 (157) 0.1 (6) Oily fishÀ 42.6 (4931) 33.0 (3823) 23.3 (2700) 1.0 (121) 0.1 (10) Shellfish` 80.7 (9351) 15.8 (1834) 3.2 (375) 0.2 (20) 0.0 (5)

*Examples given in question were ‘‘cod, haddock, plaice, fish fingers, etc’’; Àexamples given in question were ‘‘pilchards, sardines, mackerel, tuna, herring, kippers, trout, salmon, etc’’; `examples given in question were ‘‘prawns, crab, cockles, mussels, etc.’’

As far as we are aware this relation has not yet been calculate n-3FA intake. Only women who consumed no examined in an English population. In this study we examine shellfish (81% of women) were included in analyses using the relation between fish intake and pregnancy outcome in a this variable. This was because shellfish tends to be large cohort of women in south west England. consumed in much smaller portions than other types of fish and the sociodemographic characteristics of women who ate METHODS shellfish differed from those of women eating other types of The data for this study were obtained from the Avon fish (data not shown). The mean weekly frequency of fish longitudinal study of parents and children (ALSPAC), a consumption for the four fish frequency groups were as geographically based cohort study that has been described in follows: FREQ0–0 portions, FREQ1–0.74 portions, FREQ2– more detail elsewhere.18 19 All pregnant women resident 2.29 portions, FREQ3–4.44 portions. within a geographically defined area of south west England with an expected date of delivery between April 1991 and Outcome variables December 1992 were eligible. Ethical approval of the study Birth weight, sex of the child, and gestation were abstracted was obtained from the ALSPAC ethics committee, and the from hospital records. Gestational age was assessed on the three local ethics committees covering the area. basis of date of last menstrual period. However, if there was a discrepancy with ultrasound assessment or other clinical Assessment of fish/n-3 consumption Information on food consumption in pregnancy was obtained indicators of two weeks or more, the clinical records were by a self completion food frequency questionnaire, sent out at reviewed and a best estimate made by an experienced 32 weeks’ gestation. Three questions inquired about fish obstetrician. The factor given the greatest weight in deciding consumption. These were ‘‘How many times nowadays do gestational age was the ultrasound assessment. Preterm birth you eat’’: (a) white fish (b) other fish (c) shellfish. Each was defined as delivery before 37 weeks’ gestation. Birth copyright. question had five pre-defined response categories: Never or weight was obtained from hospital records. Low birth weight rarely, once in 2 weeks, 1–3 times per week, 4–7 times per (LBW) was defined as a birth weight of less than 2500 g. week, more than once a day. These were converted to Birth weight was adjusted for gestational age and sex assumed weekly frequencies of consumption as follows: (BWGA) using the residuals method. We defined IUGR as a Rarely or never = 0, once in 2 weeks = 0.5, 1–3 times per BWGA that was below the 10th centile. This was done with week = 2, 4–7 times per week = 5.5, more than once a reference to our own sample, not to an external standard—as day = 10. The answers to these questions were used to we had such a large population based sample this was felt to estimate the n-3FA intake from fish. This was done by be appropriate. assuming a standard composition for each portion of white fish, oily fish, and shellfish, which would yield 0.32 g n-3FAs Confounding variables from a portion of white fish, 0.89 g from a portion of oily fish, Information on maternal smoking in pregnancy (at http://jech.bmj.com/ 20 and 0.34 g from a portion of shellfish. The answers to the 32 weeks’ gestation), alcohol drinking in pregnancy question on oily fish consumption were validated by (assessed during first three months), highest educational comparison with the erythrocyte fatty acid composition of qualification, whether or not the mother was living with a blood samples obtained during pregnancy—the docosahexa- partner, height, parity, and pre-pregnant weight was enoic acid content of the erythrocytes increased significantly obtained by questionnaire. Parity was measured as the with increasing frequency of consumption of oily fish number of previous pregnancies that the mother had had 21 (p,0.001). that resulted in either a live birth or a stillbirth. Maternal age The women were divided into six groups according to at delivery was derived by subtracting the mother’s date of on September 26, 2021 by guest. Protected their calculated weekly intake of n-3FAs (QUANT0 to birth from the child’s date of birth. These variables were QUANT5), with women in QUANT0 consuming no seafood classified as follows: smoking (0, 1–9, >10 cigarettes per and the other five groups being fifths of the remaining day), drinking (no alcohol, ,1 glass per week, 1+glasses per women. The estimated mean daily fish intake across all week), maternal age at delivery ((19, 20–29, 30–39, >40 women was 32.8 g, corresponding to a mean daily n-3FA years), parity (0, >1), height ((159, 160–169, 170–179 and intake of 0.147 g. The mean daily fish intakes calculated >180 cm), pre-pregnant weight ((49, 50–59, 60–69, 70–79, for the six groups were: QUANT0–0 g, QUANT1–9.7 g, and >80 kg), education (low—CSE or no qualifications; QUANT2–15.6 g, QUANT3–33.8 g, QUANT4–45.4 g, QUANT5– medium—vocational qualifications or O level; high—A level 77.4 g. Table 2 shows the mean daily n-3FA intakes in each or degree), and cohabitant status (that is, living with a group. partner, yes/no). The women were also divided into four groups on the basis of their combined frequency of consumption of white and oily fish. One group consisted of women who ate no fish Statistical analyses (FREQ0), the other groups were as near as possible thirds of Only singleton liveborn babies were included in these the remaining women (FREQ1-3). This second method of analyses. Women who reported taking fish oil supplements categorisation was used as it did not require most of the at any point during pregnancy were excluded from the assumptions about portion size and n-3 content needed to analyses.

www.jech.com www.jech.com 488

Table 2 Maternal characteristics according to quantile of n-3 fatty acid intake. Values are percentages (n)

n-3 fatty acid intake

Quantile Mean (range) (g) Smoker* Low educationÀ Primiparous Single` ,50 kg1 Height,1.6 m Teenager Non-drinker**

0 (n = 1536) 0.000 (0.00–0.00) 30.5 (469) 32.0 (487) 48.2 (703) 10.4 (145) 18.6 (261) 28.9 (411) 8.1 (124) 50.8 (743) 1 (n = 1997) 0.025 (0.02–0.05) 25.3 (506) 28.8 (571) 45.0 (857) 7.9 (148) 14.0 (257) 28.6 (534) 5.6 (112) 46.4 (892) 2 (n = 1926) 0.084 (0.06–0.09) 18.6 (358) 16.6 (318) 46.6 (865) 6.0 (111) 11.8 (216) 22.5 (416) 2.6 (50) 42.3 (794) 3 (n = 1800) 0.099 (0.09–0.12) 21.1 (379) 23.5 (421) 43.0 (748) 6.2 (106) 14.3 (241) 24.8 (426) 3.9 (71) 45.1 (794) 4 (n = 2027) 0.198 (0.16–0.28) 14.7 (297) 13.0 (262) 43.0 (847) 3.8 (74) 12.0 (231) 23.4 (457) 2.5 (51) 43.9 (873) 5 (n = 2299) 0.395 (0.29–2.23) 12.8 (294) 11.1 (255) 42.5 (952) 4.0 (90) 12.6 (273) 20.7 (457) 2.0 (45) 44.9 (1012) p x2 ,0.001 ,0.001 0.002 ,0.001 ,0.001 ,0.001 ,0.001 ,0.001 p linear trend ,0.001 ,0.001 ,0.001 ,0.001 0.581 ,0.001 ,0.001 0.015

*Mother smokes one or more cigarettes per day at 32 weeks gestation; Àmother’s highest educational qualification Certificate of Secondary Education or no qualifications; `mother does not live with partner; 1maternal pre-pregnancy weight under 50 kg; mother aged ,20y at delivery; **drank no alcohol during the first three months of pregnancy.

Table 3 Frequency of low birth weight, preterm delivery, and intrauterine growth retardation and mean (SD) birth weight, gestation length, and birth weight adjusted for length of gestation, according to quantile of n-3 fatty acid intake

Quantile of n-3 fatty acid intake LBW% (n) Preterm% (n) IUGR% (n) Birth weight (g) Gestation (weeks) Adjusted* birth weight (g)

0 (n = 1536) 4.4 (66) 4.4 (68) 12.4 (187) 3385 (539) 39.5 (1.7) 3373 (463) 1 (n = 1997) 4.8 (94) 4.7 (94) 10.6 (210) 3402 (539) 39.5 (1.8) 3398 (455) 2 (n = 1926) 4.3 (81) 5.1 (98) 9.0 (171) 3433 (528) 39.5 (1.8) 3423 (438) 3 (n = 1800) 4.7 (84) 4.9 (88) 9.1 (162) 3426 (516) 39.5 (1.7) 3420 (442) 4 (n = 2027) 3.4 (68) 4.1 (84) 7.8 (156) 3458 (502) 39.6 (1.7) 3434 (434) 5 (n = 2299) 3.3 (75) 4.2 (97) 7.7 (175) 3463 (518) 39.5 (1.7) 3448 (438)

p x2 0.064 0.660 ,0.001 ,0.001À 0.386` ,0.001 al et Ness, Emmett, Rogers, p linear trend 0.011 0.378 ,0.001 ,0.001 ,0.001 Adj p linear trend1 0.311 0.684 0.083 0.215 0.427

*Adjusted for sex and gestation; Àp value by analysis of variance; `p value by Kruskal-Wallis; 1p value adjusted for sex of infant, maternal smoking, age, parity, height, pre-pregnant weight, education, cohabitant status, and alcohol

consumption.

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Univariate analyses Mean birth weight and gestation, and the frequency of LBW, preterm delivery and IUGR in the different n-3FA intake and fish consumption groups were compared using one way analysis of variance and the Kruskal-Wallis test for contin- uous variables, and x2 analysis and binary logistic regression for categorical variables. birth weight

Multivariate analyses * In the multivariate analyses, the ORs for LBW, preterm 0.001 delivery, and IUGR in the different n-3FA and fish intake 0.001 3451 (433) 3435 (439) 3417 (442) 3373 (463) Adjusted , 0.356 groups were calculated using logistic regression, adjusting for , sex of the child and the confounding variables listed above. The adjusted ORs were also calculated separately for non- smokers only, as one study has suggested that the relation between n-3FA intake/status and birth outcome might be restricted to non-smokers.6

RESULTS The 32 week questionnaire was returned by 12441 women 39.5 (1.7) 39.5 (1.7) 39.5 (1.8) 39.5 (1.7) Gestation (weeks) out of 14 150 pregnancies reaching 32 weeks (87.9%), of 0.846 whom 12 200 (86.2%) had completed the questions on fish intake. Excluding still births reduced the sample to 12 174 (86.0%), excluding multiple births reduced the sample to 11 851 (83.8%), and excluding women who took fish oil supplements reduced the sample to 11 585 (81.9%). Information on all confounding variables was available for 10 040 (71.0%) women—this formed the sample for the multivariate analyses. Table 1 shows the frequency with which white fish, oily 0.001 0.001 3460 (510) 3454 (507) 3423 (531) 3385 (539) Birth weight , 0.360 fish, and shellfish were consumed. White fish was eaten at , least once in two weeks by 81.6% of women, as compared with 57.4% eating oily fish, and 19.3% eating shellfish. copyright. Table 2 shows the relation of the confounding variables with n-3FA intake. The proportion of smokers, less educated mothers, primiparas, single women, short women, teenage mothers, and non-drinkers were all lower among women with higher n-3FA intake. The proportion of women with a 0.001 0.001 7.1 (103) 8.2 (223) 9.4 (335) 12.4 (187) IUGR% (n) , , low pre-pregnant weight also varied significantly with n-3FA 0.017 intake, although the relation was not linear. Table 3 shows the occurrence of LBW, preterm delivery, and IUGR by quantile of n-3FA intake, as well as the mean birth weight, gestation, and BWGA. As n-3FA intake

increased there was a significant fall in the frequency of http://jech.bmj.com/ LBW and IUGR. There was also a small but significant increase in mean birth weight and mean BWGA, which increased by about 70–80 g between the children of mothers eating no fish or shellfish and those in the highest quantile of 4.5 (66) 4.4 (122) 5.0 (178) 4.4 (68) Preterm% (n) 0.724 0.714 0.418 n-3FA intake. However, there was no association with the frequency of preterm birth or mean gestation. On adjusting for potential confounders the associations between n-3FA

intake and mean birth weight, LBW, BWGA, and IUGR lost on September 26, 2021 by guest. Protected significance. Similar results were obtained using grouped frequency of white and oily fish intake (table 4). Mean birth weight and 3.3 (48) 3.8 (103) 4.4 (156) 4.4 (66) LBW% (n) 0.260 0.064 mean BWGA increased and the frequency of IUGR declined 0.492 as frequency of fish intake increased, and there was a small non-significant (p = 0.064) fall in the frequency of LBW. p value adjusted for sex of infant, maternal smoking, age, parity, height, pre-pregnant weight, education, cohabitant status, and alcohol consumption. À However, the frequency of preterm birth and mean length of gestation was unassociated with frequency of fish intake. On adjustment the association between mean birth weight or BWGA and frequency of fish intake lost significance. However, the reduction in the proportion of infants with À

IUGR with increasing fish intake remained significant in the Frequency of low birth weight (LBW), preterm delivery, and intrauterine growth retardation (IUGR) and mean (SD) birth weight, mean gestation length, and mean birth weight adjusted analysis. Table 5 shows the crude and adjusted ORs for preterm 2 birth, LBW, and IUGR by quantile of n-3FA intake. There was x Adjusted for sex and gestation; p FREQ3 (n = 1471) FREQ2 (n = 2753) FREQ1 (n = 3591) FREQ0 (n = 1536) p linear trend * Adj p linear trend adjusted for length of gestation, according to frequency of fish intake. Only those mothers who ate no shellfish included in the analysis no association between n-3FA intake and the likelihood of Table 4 preterm birth, in either adjusted or unadjusted analyses. In

www.jech.com 490 Rogers, Emmett, Ness, et al J Epidemiol Community Health: first published as 10.1136/jech.2003.013565 on 13 May 2004. Downloaded from

unadjusted analysis there was a significant drop in the OR for LBW and IUGR with increasing n-3FA intake. On adjustment these relations were considerably attenuated and lost statistical significance, for example the OR of LBW in the 0.001 1 , p lowest compared with the highest quantile of n-3FA intake fell from 1.33 to 1.08, and the equivalent figures for IUGR were 1.69 to 1.20. However, there was still some suggestion * 1.00 0.083 1.00 0.083 1.00 0.004 1.00 1.00 0.186 1.00 0.311 1.00 0.041 1.00 0.011 1.00 0.649 1.00 0.684 1.00 0.231 1.00 0.378 of a graded reduction in the ORs for IUGR with increasing n-3FA intake. The logistic regression analysis was repeated using frequency of fish intake as the predictor (table 6). There was no significant association between frequency of fish intake and the occurrence of preterm birth and LBW in either univariate or multivariate analysis. However, there was a significant decrease in the OR for IUGR as frequency of fish intake increased, with ORs significantly greater than one in the FREQ0 and FREQ1 groups. This relation retained 0.96 (0.73 to 1.28) 0.94 (0.73 to 1.20) 0.98 (0.75 to 1.27) 1.01 (0.81 to 1.27) 0.86 (0.56 to 1.32) 0.96 (0.66 to 1.39) 0.93 (0.63 to 1.38) 1.03 (0.74 to 1.44) 0.93 (0.65 to 1.33) 0.93 (0.68 to 1.28) 1.01 (0.73 to 1.41) 0.98 (0.73 to 1.32) 45 statistical significance but was considerably attenuated on adjusting for potential confounders, for example, the OR for IUGR in the lowest compared with the highest fish intake group fell from 1.85 to 1.37. The association between fish intake and IUGR was unchanged by the inclusion of ethnic group of the child as a confounding variable (5% of the cohort were of non-white ethnic origin). The ORs for preterm delivery, LBW, and IUGR according to n-3FA intake or frequency of fish consumption among non- 1.01 (0.75 to 1.36) 0.93 (0.72 to 1.19) 1.14 (0.88 to 1.50) 1.19 (0.96 to 1.49) 1.27 (0.84 to 1.91) 1.32 (0.93 to 1.89) 1.35 (0.92 to 1.96) 1.45 (1.05 to 1.99) 1.13 (0.79 to 1.62) 1.10 (0.80 to 1.51) 1.24 (0.89 to 1.73) 1.17 (0.87 to 1.57) smokers only (tables 5 and 6) were similar to those obtained for all subjects. The effect of n-3FA/fish consumption was if anything more pronounced among the whole sample than among non-smokers only. These results did not suggest that any possible effect of n-3FA or fish intake on pregnancy outcome was restricted to or stronger among non-smokers than among smokers. copyright.

DISCUSSION 1.13 (0.85 to 1.49) 1.05 (0.83 to 1.34) 1.16 (0.89 to 1.51) 1.18 (0.95 to 1.47) 1.29 (0.87 to 1.91) 1.33 (0.94 to 1.88) 1.26 (0.87 to 1.84) 1.30 (0.94 to 1.79) 1.19 (0.85 to 1.67) 1.20 (0.88 to 1.63) 1.22 (0.88 to 1.69) 1.22 (0.91 to 1.62) In this study we found no association between intake of n-3FAs or fish in late pregnancy and the duration of gestation or the frequency of pre-term birth in either crude or adjusted analyses. In univariate analysis fish/n-3FA consumption was p for linear trend.

1 positively associated with birth weight, with an increase of around 80 g between the lowest and highest n-3FA intake groups, and negatively associated with the frequency of IUGR. The relation with birth weight was lost on adjustment

for potential confounders. The relation between n-3FA or fish http://jech.bmj.com/ intake and the frequency of IUGR was considerably attenuated on adjustment for potential confounders, however, the reduction in the odds of IUGR with increasing fish intake remained statistically significant. The fact that there was a significant association between fish intake and IUGR but not between BWGA and IUGR suggests that fish intake has an effect specifically on the right hand tail of the birth weight

distribution, rather than shifting the whole distribution. on September 26, 2021 by guest. Protected

adjusted for sex of infant, maternal smoking, age, parity, height, pre-pregnant weight, education and cohabitant status, and alcohol consumption (analyses in non-smokers only not adjusted Overall it seems that most of the observational studies À 0123 Quantile of n-3 fatty acid intake from fish relating fish intake to pregnancy outcome, including our own, have found a moderate positive effect on fetal growth rate but little or no effect on gestation. In contrast, fish oil 9923 1.20 (0.93 to 1.55) 1.06 (0.83 to 1.35) 11444 1.69 (1.36 to 2.10) 1.42 (1.15 to 1.76) 9923 1.08 (0.73 to 1.59) 1.20 (0.84 to 1.72) 11444 1.33 (0.95 to 1.87) 1.46 (1.07 to 1.99) 10040 0.85 (0.59 to 1.22) 0.95 (0.68 to 1.31) 9282 1.14 (0.79 to 1.65) 1.18 (0.85 to 1.65) 11585 1.05 (0.77 to 1.44) 1.12 (0.84 to 1.50) supplementation trials have tended to find a positive effect on gestation and little or no effect on fetal growth. Indeed, there has been some evidence from supplementation trials that n-3FAs might have a detrimental effect on fetal growth. ` There are several possible explanations for these differences. non-smokers—that is, smoking 0 cigarettes per day at 32 weeks’ gestation;

` It may be that some constituent of fish other than n-3FAs is NonSm 8140 1.24 (0.91 to 1.69) 1.13 (0.85 to 1.51) All NonSm 9165 1.42 (1.08 to 1.88) 1.23 (0.95 to 1.59) All NonSm 8140 1.11 (0.70 to 1.75) 1.25 (0.82 to 1.89) All NonSm 9165 1.33 (0.88 to 2.01) 1.31 (0.90 to 1.91) All NonSm 8241 1.00 (0.67 to 1.49) 1.03 (0.72 to 1.49) All NonSm All responsible for the association of fish intake with birth weight. Alternatively, there may be a threshold effect. In Odds ratios (95%CI) for preterm delivery, low birth weight, and intrauterine growth retardation (IUGR) by quantile of n-3 fatty acid intake. IUGR was defined as having a birth À À À nearly all the supplementation studies the doses of n-3F As given were considerably higher than would be consumed at even the highest levels of fish intake, and it is possible Highest intake category is the reference category; for smoking status); * Adjusted IUGR Crude Adjusted Low birth weight Crude Adjusted Preterm birth Crude Birth outcome Smoking status n weight below the 10th centile for sex and gestational age Table 5 that effects on gestation are not observable at the lower intakes of n-3FAs achievable by eating fish. In several of the

www.jech.com Fish intake in pregnancy and birth weight 491 J Epidemiol Community Health: first published as 10.1136/jech.2003.013565 on 13 May 2004. Downloaded from observational studies relating fish intake to birth weight there was a failure to control for socioeconomic status, which is associated with both birth outcome22 23 and dietary intakes.24 0.027 0.070 0.492 0.179 0.004 0.017 0.417 0.418 0.714 0.063 0.872 0.001 1 p , Limitations of this study The study design was limited in its ability to detect a relation between fish intake and very preterm birth as the food frequency questionnaire was not sent out until 32 weeks’ gestation, thus any births before this time point were not included in the analysis. Conversely, ability to detect an effect 1.00 1.00 1.00 1.00 FREQ4 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 of high fish intake on prolonging gestation might be affected by the current practice of inducing labour at 42 weeks’ gestation. Information on how labour started was available for a random sample of 1418 of the ALSPAC mothers. Labour was induced rather than spontaneous in 19% of all births, and in 22% of preterm births. It is possible that this may have obscured any associations between fish intake and preterm birth or mean duration of gestation. The question on oily fish consumption did not distinguish between tuna and other types of oily fish—tuna has a much lower content of n-3FAs than other oily fish,20 and in this respect is comparable to white fish. Including a separate question on tuna would have permitted more accurate calcu- 0.96 (0.66 to 1.37) 1.17 (0.92 to 1.49) 1.09 (0.80 to 1.48) 0.99 (0.73 to 1.34) 1.15 (0.81 to 1.63) 1.09 (0.72 to 1.65) 1.07 (0.73 to 1.58) 0.98 (0.69 to 1.20) 1.12 (0.85 to 1.48) 1.05 (0.81 to 1.38) FREQ2 1.06 (0.75 to 1.50) 0.91 (0.66 to 1.27) lation of probable n-3FA intakes, reducing measurement error and making any possible associations between n-3FA and birth outcome easier to observe. Another limitation of the study design is the limited ability to distinguish between levels of fish intake at the lowest end of the exposure scale— the lowest intake categories for each dietary variable were ‘‘never or rarely’’ and ‘‘once in 2 weeks’’. In the recent Danish study9 the lowest categories for each dietary variable

were ‘‘never’’, ‘‘less than once a month’’ and ‘‘1–3 times a copyright. month’’ enabling the researchers to distinguish between low levels of fish intake. Furthermore, there is a possibility that some bias may have been introduced by missing data—of the 1.08 (0.76 to 1.52) 1.36 (1.08 to 1.72) 1.25 (0.93 to 1.67) 1.11 (0.83 to 1.48) 1.34 (0.97 to 1.87) FREQ1 1.31 (0.89 to 1.93) 1.25 (0.86 to 1.80) 1.32 (0.87 to 2.00) 1.26 (0.96 to 1.65) 1.17 (0.91 to 1.51) 1.18 (0.85 to 1.63) 1.01 (0.74 to 1.38) 12 441 women who returned the questionnaire, only 10 040 had complete information on fish consumption and all confounding variables. It is possible that uncontrolled confounding might have obscured a true relation between fish intake and gestation, or created a spurious relation * between fish intake and IUGR. One possible confounder for which we were unable to control was intrapartum weight p for linear trend.

1 gain, as these data were not available for most of our sample. http://jech.bmj.com/ Further observational studies of fish intake and pregnancy outcome in a range of populations are needed to help investigate this last possibility. This would allow the relation to be examined in populations with different levels of fish FREQ0 Frequency of fish intake intake, and different patterns of association between fish consumption and other confounders. The effect of seafood and n-3FAs on a range of other

outcomes has recently received increased attention, for on September 26, 2021 by guest. Protected 9238 1.85 (1.44 to 2.38) 6577 1.40 (1.00 to 1.98) 9351 0.99 (0.70 to 1.39) 9238 1.33 (0.91 to 1.95) 7390 1.41 (0.89 to 2.23) 8012 1.07 (0.69 to 1.65) 6577 1.18 (0.71 to 1.97) 7390 1.53 (1.12 to 2.09) 8012 1.37 (1.02 to 1.84) 7484 1.11 (0.74 to 1.66) 8105 0.76 (0.52 to 1.13) example the possible relations between n-3FA intake and eyesight development,21 mental health, and behavioural adjusted for sex of infant, maternal smoking, age, parity, height, pre-pregnant weight, education, cohabitant status, and alcohol consumption (analyses in non-smokers not adjusted for smoking À outcomes.25 26 In the ALSPAC cohort it has been found that the children of mothers who ate oily fish during pregnancy

` were more likely to have achieved adult stereoacuity at the age of 3 years.21 Follow up of this and other cohort studies will show whether fish consumption in pregnancy has other Smoking status n All NonSm All All NonSm Non-smokersNonSm 6659 0.95 (0.61 to 1.46) All NonSm NonSm All All long term effects on the fetus.

ACKNOWLEDGEMENTS We are extremely grateful to the mothers who have taken part in this study, and to the midwives for their cooperation, and help in

OR (95% CI) for preterm birth, low birth weight, and IUGR by frequency of fish intake (non-shellfish eaters only). IUGR was defined as being below the 10th centile of birth weight for recruiting the mothers during pregnancy. We would like to acknowl- non-smoker—that is, smoking 0 cigarettes per day at 32 weeks’ gestation; À À À

` edge the dedicated work of the ALSPAC study team; this includes interviewers, computer technicians, clerical workers, research scien-

Highest intake category is reference category; tists, volunteers, and managers. The ALSPAC study is part of the status); * Adjusted IUGR Crude Adjusted Preterm birth Crude Low birth weight Crude Birth outcome Adjusted sex and gestational age Table 6 WHO initiated European longitudinal study of pregnancy and childhood.

www.jech.com 492 Rogers, Emmett, Ness, et al

...... J Epidemiol Community Health: first published as 10.1136/jech.2003.013565 on 13 May 2004. Downloaded from 12 Kristal AR, Rush D. Maternal nutrition and duration of gestation: a review. Authors’ affiliations Clin Obstet Gynecol 1984;27:553–61. I Rogers, P Emmett, A Ness, J Golding, ALSPAC Study Team, Unit of 13 Onwude JL, Lilford RJ, Hjartardottir H, et al. A randomised double blind Paediatric and Perinatal Epidemiology, Division of Community placebo controlled trial of fish oil in high risk pregnancy. Br J Obstet Gynaecol Medicine, University of Bristol, Bristol, UK 1995;102:95–100. 14 Bulstra-Ramakers MTEW, Huisjes HJ, Visser GHA. The effects of 3 g Funding: the ALSPAC study could not have taken place without the eicosapentaenoic acid daily on recurrence of intrauterine growth retardation financial support of the University of Bristol, the MRC, the Wellcome and pregnancy induced hypertension. Br J Obstet Gynaecol Trust, the Department of the Environment, MAFF, various medical 1994;102:123–6. charities and commercial companies. 15 Leaver HA, Lytton FD, Dyson H, et al. The effect of dietary w3 and w6 polyunsaturated fatty acids on gestation, parturition and prostaglandinE2in Conflicts of interest: none declared. intrauterine tissues and the kidney. Prog Lipid Res 1986;25:143–6. 16 Olsen SF, Hansen HS, Jensen B. Fish oil versus arachis oil food supplementation in relation to pregnancy duration in rats. Prostaglandins REFERENCES Leukot Essent Fatty Acids 1990;40:255–60. 1 Olsen SF, Hansen HS, Swrensen TIA, et al. Intake of marine fat, rich in (n-3)- 17 Clarke SD, Benjamin L, Bell L, et al. Fetal growth and fetal lung phospholipid polyunsaturated fatty acids, may increase birthweight by prolonging content in rats fed safflower oil, menhaden oil or hydrogenated coconut oil. gestation. Lancet 1986;i:367–9. Am J Clin Nutr 1988;47:828–35. 2 Harper V, MacInnes R, Campbell D, et al. 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