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Effects of n-3 polyunsaturated fatty acid supplementation in pregnancy on maternal and fetal erythrocyte fatty acid composition

Abstract

Objective: The aim of this study was to assess the effects of fish oil supplementation in pregnancy on maternal erythrocyte fatty acid composition at different stages of pregnancy and in the post-partum period, and on neonatal erythrocyte fatty acid composition.

Design: A double-blind, randomised, placebo-controlled study.

Setting: Subiaco, Western Australia.

Subjects: In all, 98 women booked for delivery at St John of God Hospital, Subiaco, were recruited from private rooms of obstetricians. In total, 83 women and their healthy full-term babies completed the study.

Interventions: Women received either 4 g of fish oil (n=52) (56% docosahexaenoic acid (DHA) and 28% eicosapentaenoic acid (EPA) or placebo (olive oil) (n=46) per day from 20 weeks gestation until delivery.

Main outcome measures: Erythrocyte phospholipid fatty acids were measured in maternal peripheral blood at 20, 30 and 37 weeks of pregnancy and at 6 weeks post partum, and from cord blood collected at birth.

Results: Compared to the control group, maternal EPA and DHA were significantly higher in the fish oil group at 30 and 37 weeks gestation, and remained elevated at 6 weeks post partum (P<0.001). The proportions of n-6 polyunsaturated (arachidonic acid, 22:3n-6 and 22:4n-6) were significantly lower in the fish oil supplemented group at the same time periods (P<0.001). Similarly, the proportions of EPA and DHA were significantly higher (P<0.001), and those of n-6 polyunsaturated fatty acids arachidonic acid, 20:3n-6, 22:3n-6 and 22:4n-6 were significantly lower (P<0.001), in erythrocytes from neonates in the fish oil group, compared to those in the control group.

Conclusions: Fish oil supplementation from 20 weeks of pregnancy until birth is an effective means of enhancing n-3 fatty acid status of both mothers and neonates. Furthermore, the changes in maternal erythrocyte fatty acid composition are retained until at least 6 weeks post partum. It is essential to assess the effects of concomitant decreases in arachidonic acid status before any dietary recommendations can be made.

Sponsorship: The study was supported by grants from the NH & MRC and Raine Medical Research Foundation, Australia.

Introduction

The long-chain polyunsaturated fatty acids (LCPUFA) are derivatives of dietary essential fatty acids and are critical for normal growth and development. During gestation, large amounts of n-3 docosahexaenoic acid (DHA; 22:6n-3) and n-6 arachidonic acid (AA; 20:4n-6) are deposited in the foetal retina and brain (Clandinin et al, 1981), and these fatty acids appear to be important for normal neuronal (Neuringer et al, 1984) and visual function (reviewed in Gibson & Makrides, 1999). Depletion of dietary DHA is associated with adverse neurological outcomes in animals (Carlson & Neuringer, 1999), suggesting that variations in maternal long-chain PUFA stores have the potential to affect foetal development (van Houwelingen et al, 1992).

An increase in the consumption of vegetable oils and spreads rich in the n-6 PUFA linoleic acid (LA; 18:2n-6) has occurred in ‘Western’ diets over the past 30–40 y (Simopoulos, 1999). In parallel with this, there has been an absolute and proportional decline in dietary n-3 PUFA intake (Simopoulos, 1999). This dietary change is reflected in the altered fatty acid composition of breast milk over time (Makrides et al, 1995). The functional effects of these compositional changes are not well understood. However, changing disease patterns during this period (Connor, 2000) have heightened awareness that alterations in dietary PUFA intake may affect many aspects of normal development (Simopoulos, 1999) and may predispose to later disease (Hodge et al, 1996; Black & Sharpe, 1997).

Fish oil is rich in the long-chain n-3 PUFA eicosapentaenoic acid (EPA; 20:5n-3) and DHA. It has been suggested that increased fish oil consumption could be a means by which the increase in the prevalence of certain diseases (eg allergic diseases) could be prevented (Hodge et al, 1996; Black & Sharpe, 1997). Although fish oil supplementation during pregnancy significantly increases foetal n-3 PUFA levels (van Houwelingen et al, 1995; Connor et al, 1996; Helland et al, 2001; Velzing-Aarts et al, 2001), the longitudinal effects of prenatal fish oil supplementation on (a) maternal PUFA status during pregnancy, (b) post-partum long-chain n-3 PUFA (especially DHA) ‘depletion’, and (c) long-term infant development and health are not known. In this double-blind, randomised, placebo-controlled study, we determined the effects of fish oil supplementation during pregnancy on the fatty acid composition of maternal erythrocytes (at different stages of pregnancy and at 6 weeks post partum) and neonatal erythrocytes.

Subjects and methods

Subjects, study design and intervention

In all, 98 women were recruited as part of a study evaluating the effect of n-3 PUFA supplementation on neonatal immune responses in babies at a high risk of developing allergic disease. The women were booked for delivery at St John of God Hospital, Subiaco, Western Australia between January 2000 and September 2001. All had a history of allergic rhinitis or asthma but were otherwise healthy. Women were excluded if they smoked, had high-risk pregnancies or ate fish more than once a week. Ethical approval for the study was granted by the Princess Margaret Hospital for Children, King Edward Memorial Hospital and St John of God Hospital Ethics Committees. All women gave written informed consent.

The women were stratified by parity (no previous term childbirth vs one or more), prepregnancy BMI, age and maternal allergy (allergic rhinitis or asthma) and randomised to supplement their usual diet with 4 g/day of fish oil or olive oil in capsules from 20 weeks gestation until delivery when supplementation was ceased. The fatty acid composition of the capsules was confirmed by gas chromatography (Table 1). Capsules containing long-chain n-3 PUFA (56% DHA and 28% EPA) were provided by Ocean Nutrition, Nova Scotia, Canada. Image-matched olive oil capsules were prepared by Pan Laboratories, Moorebank, New South Wales, Australia. Women in the fish oil group consumed about 1.1 g EPA plus 2.2 g DHA/day. This dose was based on previous trials studying the effect of n-3 PUFA supplementation in pregnancy (Olsen et al, 1992), on high-risk pregnancies (Onwude et al, 1995), on blood pressure (Salvig et al, 1996) and in our previous studies (Mori et al, 1997). The dose was approximately equivalent to one fatty fish meal per day (Mori et al, 1997). All capsules contained α-tocopherol (3–4 mg/g oil) as an antioxidant.

Table 1 Fatty acid composition of fish oil and olive oil capsulesa

Olive oil was chosen as the most suitable lipid for placebo control. Although some minor immunological effects have been reported with olive oil (Yaqoob et al, 1998), the amount added (4 g/day) through supplementation does not significantly alter the average daily intake of oleic acid (around 26 g/day) in Australian diets (CSIRO, 1996).

Data and blood sample collections

Medical history, family medical history and demographic information were gathered at recruitment. Compliance was assessed by capsule count. Maternal fasting blood samples were collected at baseline (20 weeks gestation), at 30 and 37 weeks gestation, and 6 weeks after delivery. Cord blood was collected at delivery.

At 20 and 30 weeks gestation, the women also completed a validated semiquantitative food frequency questionnaire (SQFFQ) (CSIRO, 1996), which determined their intake of 11 different fish products during the previous 1 month. These data were used to identify any background dietary change of fish consumption in each group.

Erythrocyte fatty acid composition analysis

Blood samples were collected into heparinized Roswell Park Memorial Institute (RPMI, Life Technology, UK) tissue culture medium and centrifuged at 500 g for 30 min. Erythrocytes were isolated from below a Lymphoprep (Nycomed Pharmacia, Norway) gradient interface and washed in phosphate-buffered saline. Fatty acid composition analyses were carried out as previously described (Mori et al, 2000). Briefly, total lipids were extracted with chloroform : methanol (2 : 1) and phospholipids isolated by thin-layer chromatography. Fatty acid methyl esters were prepared by treatment of phospholipid extracts with 4% H2SO4 in methanol at 90°C for 20 min and analysed by gas liquid chromatography using a Hewlett-Packard model 5980A gas chromatograph. The column was a BPX70 (25 m × 0.32 mm, 0.25 μm film thickness) (SGE, Ringwood, Victoria, Australia) with a temperature programmed from 150 to 210°C at 4°C/min and using N2 as the carrier gas at a split ratio of 30 : 1. Peaks were identified by comparison with a known standard mixture. The fatty acids are expressed as a percentage of the weight of the total fatty acids measured (C14–C22).

Statistical analysis

All statistical analyses were performed using SPSS (SPSS Inc, Chicago, USA) software. Independent t-tests were used to determine significant differences in continuous variables between the two groups. Differences in categorical variables were determined by the Pearson χ2 test. The effect of treatment and time on fatty acid composition was examined using GLM repeated measures with Bonferroni correction for multiple comparisons. Owing to samples not collected at one or more time points (n=12) repeated measures analysis was performed on 73 full sets of maternal samples, including 36 in the fish oil group and 37 in the control group. A paired t-test was used for within-group analyses when a significant group × time interaction was shown. Maternal and neonatal fatty acid relationships were determined by Pearson correlation and differences between the two groups were determined by paired t-tests on 81 pairs of data: 39 in the fish oil group and 42 in the control group. P<0.05 was considered statistically significant for the analysis of pregnancy outcome variables. P<0.01 was considered statistically significant for all fatty acid analyses because of the number of comparisons made.

Results

Maternal characteristics

Four mothers whose babies were delivered before 36 weeks gestation were excluded from the analysis. Two infants with significant disease were excluded from the analysis. One required chemotherapy for a malignant condition (multisystem Langerhan's histiocytosis) and the other died of a degenerative neurological condition (with progressive leucodystrophy) at several months of age. Although both were in the fish oil group, neither condition was linked in any apparent way to the dietary supplementation. Seven women in the fish oil group and one in the control group withdrew from the study due to nausea, which they attributed to consumption of the capsules. Cord blood was not collected at one delivery. Totally, 83 mothers and their healthy full-term babies completed the study; 40 in the fish oil group and 43 in the control group.

The characteristics of mothers completing the study are shown in Table 2. There were no significant differences in maternal age, prepregnancy BMI, atopic status or parity between the women in the fish oil and control groups. There were no significant differences in gestational age, birth weight, birth length, head circumference or gender between the neonates in the two groups (Table 3). Background dietary intake assessed by food frequency questionnaires was not different between the two groups at study entry or at 30 weeks gestation. At study entry, median (interquartile range) fish intake was 0.9 (0.6–2.4) meals per week in the control group and 1.4 (1–2.4) meals per week in the fish oil group. At 30 weeks gestation, fish intake was 0.9 (0.4–1.7) meals per week in the control group and 1.2 (0.8–2.4) meals per week in the fish oil group.

Table 2 Characteristics of the women who completed the study
Table 3 Characteristics of the neonates who completed the study

Maternal erythrocyte phospholipid fatty acid composition

Table 4 and Figure 1 show the phospholipid fatty acid composition of maternal erythrocytes at 20, 30 and 37 weeks gestation and at 6 weeks post partum expressed as a percentage of the total fatty acids measured. Table 4 also shows the sums of the proportions of various fatty acid classes and the ratios between them.

Table 4 Erythrocyte fatty acids in women supplemented with fish oil or olive oil (control) in pregnancy at 20, 30 and 37 weeks gestation and 6 weeks post partum (PP)a
Figure 1
figure1

Change in relative fatty acid composition of maternal erythrocytes (at 30 and 37 weeks gestation, and 6 weeks post-partum) from baseline (20 weeks gestation). Values shown are the mean change from the baseline as a percentage of total fatty acids (±s.e.m.) in n-3 PUFA-supplemented women (n=36) (closed squares) and the control group (n=37) (open circles). *P<0.01 for significant difference from baseline.

At 30 and 37 weeks gestation, supplementation with fish oil significantly increased the proportions of EPA and DHA and significantly decreased the proportions of all n-6 fatty acids, relative to 20 weeks gestation 1 and Table 4).

At 6 weeks post partum, the proportions of EPA and DHA in erythrocyte phospholipids remained significantly higher in the fish oil group compared to the control group, even though supplementation had ceased at delivery (Table 4). Furthermore, at 6 weeks post partum, the proportions of AA, 22:3n-6 and 22:4n-6 in the fish oil supplemented group remained significantly lower than in the control group (Table 4). However, there were no differences in the proportions of LA (18:2n-6) or dihomo-γ-linolenic acid (DGLA; 20:3n-6) between the groups 6 weeks post partum.

The sum of n-3 PUFA (EPA+DHA+22:5) and the ratio of n-3 to n-6 PUFA, in erythrocyte phospholipids, were significantly higher in women supplemented with fish oil compared to control subjects at 30 and 37 weeks gestation and 6 weeks post-partum (P<0.001) (Table 4).

There was no association between PUFA composition and parity in either group.

The proportion of oleic acid (18:1n-9) in maternal erythrocytes was not altered by supplementation with olive oil in the control group (Table 4).

Neonatal erythrocyte phospholipid fatty acid composition

Table 5 shows the phospholipid fatty acid composition of neonatal erythrocytes. Fish oil supplementation during pregnancy resulted in significantly higher ratios of total n-3 to n-6 PUFA in cord blood erythrocytes than in the control group. In the fish oil group, the proportions of both EPA and DHA in cord blood erythrocyte phospholipids were significantly higher. Conversely, the proportions of cord blood 20:3n-6, 22:3n-6, 22:4n-6 and AA were lower in the fish oil group. The proportion of 18:2n-6 was significantly higher in the fish oil group.

Table 5 Erythrocyte phospholipid fatty acids in cord blood from neonates of women supplemented with fish oil or olive oil (control)a

The proportions of saturated fatty acids and of oleic acid were not different in cord blood erythrocyte phospholipids in the two groups (Table 5).

Relationship between maternal and neonatal PUFA status

In the control group, the proportion of DHA was significantly higher in neonatal erythrocytes than in maternal erythrocytes at 37 weeks (P<0.001). This difference was not significant in the fish oil group (P=0.05). There was a significant positive correlation between maternal DHA at 37 weeks and neonatal DHA in both the fish oil (r=0.43, P<0.01) and the control groups (r=0.51, P<0.01). However, the uptake of DHA by the neonate relative to the mother was decreased when maternal DHA was greater than 8.87% of total fatty acids determined from the regression slope equation (y=−0.445x+3.947) in Figure 2. There was also a significant positive correlation between maternal and neonatal EPA in the fish oil (r=0.55, P<0.001) and the control groups (r=0.60, P<0.001).

Figure 2
figure2

Relationship between erythrocyte 22:6n-3 (DHA) composition in cord blood and maternal blood at 37 weeks gestation. Cord blood DHA is shown as the difference from maternal DHA expressed as the percentage of total fatty acids measured. Maternal DHA is expressed as a percentage of the total fatty acids measured. Subjects in the fish oil-supplemented group (n=39) appear as closed circles, and controls (n=42) appear as open circles. The dashed line illustrates the ‘saturation point’ of preferential uptake of DHA by the foetus from the mother, calculated from the regression slope equation when y=0.

The proportions of AA, 20:3n-6, 22:3n-6 and 22:4n-6 were higher in neonatal erythrocytes than in those from their mothers in both groups (P<0.001). A significant positive relationship between maternal and neonatal AA was seen in the fish oil group (r=0.65, P<0.001). Inverse relationships between maternal DHA and EPA and neonatal AA were also seen in the fish oil group (DHA, r=−0.47, P<0.01; EPA r=−0.55, P<0.001).

Relationship between neonatal fatty acid composition and birth outcomes

Neonatal AA, EPA and DHA were not related to birth weight, birth length or length of gestation (data not shown). This lack of relationship was retained if all of the infants completing the intervention (n=90) were included in the analysis.

Discussion

There has been considerable interest in the LCPUFA requirements of both preterm (reviewed in Gibson et al, 2001) and term infants (reviewed in Gibson & Makrides, 1999); however, the needs of mothers has received little attention. While there may be a steady decline in n-3 PUFA levels during pregnancy (Al et al, 1995a) there is also a clear decline in maternal DHA in the post-partum period (Otto et al, 1999; Makrides & Gibson, 2000) when mothers also provide the primary source of LCPUFAs for breast-fed infants. To our knowledge, this is the first report of the effects of fish oil supplementation in pregnancy on post-partum maternal PUFA status.

Although supplementation with fish oil ceased at delivery, maternal DHA (and EPA) remained significantly higher in the fish oil group compared with the control group 6 weeks post partum. Maternal plasma DHA content commonly declines during pregnancy (Al et al, 1995a; Otto et al, 1997; Matorras et al, 2001), particularly in later pregnancy (Knopp, 1991) when foetal requirements for LCPUFA are highest (Clandinin, 1999; Al et al, 2000). In the current study, this pattern was not observed in the control group, possibly because the initial maternal stores were higher than reported in other populations (Matorras et al, 2001). Under less optimal conditions, maternal stores could be significantly compromised, and may not be readily replenished in the post-partum period, particularly with the demands of breastfeeding. Over 80% of the mothers in the present study were still breastfeeding 6 weeks post partum, and the postnatal decrease in DHA status has been shown to be greater in lactating women (Otto et al, 2001). This potential DHA deficit may be more significant in multiparous compared to nulliparous women (van Houwelingen et al, 1999), suggesting long-term effects and inadequate repletion. In this study, we found no association between parity and PUFA composition. Our findings suggest that n-3 PUFA supplementation could prevent DHA depletion associated with pregnancy. This might provide benefits to the foetus and the neonate (Al et al, 1995b). However, the benefits of the fish oil-induced increase in EPA status are less clear.

This study demonstrates that fish oil supplementation commencing from 20 weeks gestation results in a significant increase in the proportions of DHA and EPA in erythrocyte phospholipid in women during pregnancy and in their neonates. This is consistent with a number of studies that have demonstrated enhanced neonatal DHA status after maternal supplementation with fish oil (Connor et al, 1996; Helland et al, 2001; Velzing-Aarts et al, 2001) or DHA-rich eggs (Borod et al, 1999). We observed a strong linear relationship between maternal and neonatal PUFA profiles in both the fish oil-supplemented group and the control group, as seen previously in both unsupplemented (Al et al, 1990; Matorras et al, 1999) and supplemented women (van Houwelingen et al, 1995; Connor et al, 1996). This relationship was evident for both n-3 and n-6 PUFA.

The relative importance of specific PUFA in normal growth and development is not clear, but balanced levels are most likely to be optimal. n-3 PUFA are widely promoted as being beneficial to human health and there is evidence that they are important for normal foetal development (Neuringer et al, 1984) and visual acuity (reviewed in Gibson & Makrides, 1999). However, it is important to emphasise that adequate levels of n-6 PUFA, such as AA, are also essential during early development (Crawford, 2000; Elias & Innis, 2001). In the present study, we observed that n-3 PUFA supplementation was associated with a concomitant decrease in the proportions of AA and other n-6 PUFA (20:3, 22:3 and 22.4), but not 18:2n-6, in cord blood. This pattern of selective effects on n-6 PUFA is consistent with previous studies (van Houwelingen et al, 1995). While AA status has been correlated to birth weight in preterm infants (Koletzko & Braun, 1991; Carlson et al, 1993), suggesting an association with intrauterine growth (Woltil et al, 1998), the present study found no relationship between the proportion of AA in neonatal erythrocytes and birth weight or birth length. Competition for the Δ-6-desaturase enzyme utilised in the metabolism of both LA to AA and EPA to DHA (Sprecher, 2000) is believed to be responsible for the low plasma AA found when fish oil is consumed (Garg et al, 1990). The opposite phenomenon is seen when maternal (Al et al, 1995b) or infant (Innis, 1991) diets are rich in n-6 PUFA. It is therefore important to consider these reciprocal effects when proposing selective supplementation with specific n-3 or n-6 PUFA, and to determine the effects on maternal health and infant development.

There is growing interest in the relationship between LCPUFA status and pregnancy and infant outcomes. We did not observe any effects of n-3 PUFA supplementation on pregnancy outcomes in this study, although others have found positive effects on length of gestation (Olsen et al, 1992) and birth weight (Olsen et al, 1994). A study by Helland et al (2001) reported that neonates with higher levels of plasma phospholipid DHA had longer gestational length. Although there are no data on long-term effects of antenatal supplementation, selective postnatal supplementation has been associated with subtle differences in neurodevelopmental outcomes. A number of studies have demonstrated improved visual and other neurological outcomes (Carlson et al, 1994; Carlson, 1999), particularly in preterm infants supplemented with DHA. DHA-supplemented infants have demonstrated more rapid information processing (on novelty preference testing) compared to the infants fed linolenic acid formulae (Carlson et al, 1996). While this suggests that DHA is beneficial, the findings also raise concerns about the unknown long-term effects of selective supplementation, particularly as many infant formulae (and other foodstuffs such as dairy products, bread and eggs) are already being supplemented with n-3 PUFA. The long-term effects of antenatal consumption of such products enriched in n-3 PUFA are not known and need to be investigated.

Epidemiological studies show variations in fatty acid status of pregnant women and their babies according to dietary intake of fish oil (Gerrard et al, 1991; Olsen et al, 1995) and this is supported by a recent review reporting moderate variations in DHA and AA in different populations (Minda et al, 2002). One recent study suggests that doses of 500 mg n-3 PUFA per day significantly increase neonatal n-3 PUFA composition without compromising the status of n-6 PUFA (Velzing-Aarts et al, 2001). Similarly, supplementation with 0.57 g DHA/day significantly increased plasma and erythrocyte DHA levels without any reduction in AA and other n-6 PUFA (Otto et al, 2000). However, it has been difficult to determine requirements since the plasma concentrations representing deficiency, sufficiency and optimal levels are not clearly defined.

Although there are clear correlations between foetal and maternal PUFA, the patterns for specific PUFA appear to vary. In this study, the proportion of AA was significantly higher in the neonates compared with their mothers, suggesting preferential transfer or a different rate of oxidation or utilisation of this PUFA to the foetus. The placenta can selectively transfer LCPUFAs to the foetal circulation (Haggarty et al, 1997; Dutta-Roy, 2000), and in the present study this apparent preferential transfer of AA was evident in the fish oil and the control groups. However, the proportion of DHA was significantly higher in neonates compared to their mothers only in the control group. This loss of concentration ‘gradient’ between the mother and foetus in the fish oil group suggests that foetal levels of DHA could be approaching ‘saturation’ which in this study appears to occur when maternal DHA proportions exceed 8.87% of the total fatty acids (Figure 2). This also suggests that increasing maternal n-3 PUFA intake and status beyond a certain level will not necessarily achieve further improvements in neonatal n-3 PUFA status; rather, this will result in a reduction in other fatty acids, such as AA. Previous evidence that incorporation of DHA in infants is saturable was reported in a double-blind randomised study which addressed the effect of DHA dose on DHA status of mothers and infants. It was reported that breast milk DHA levels above 0.8% of total fatty acid levels resulted in little increase in infant plasma or erythrocyte DHA levels (Gibson et al, 1997).

In summary, this study shows that consumption of fish oil providing 1.1 g EPA and 2.2 g DHA/day from 20 weeks of pregnancy until birth significantly alters the fatty acid composition of maternal and neonatal erythrocytes, and that this is partially sustained until at least 6 weeks post partum. While supplementation may help maintain maternal n-3 PUFA stores during breastfeeding and with successive pregnancies, it is still not clear if associated changes in neonatal fatty acid status have functional effects on the developing infant. The only previous study to address this found neither beneficial nor harmful effects of maternal fish oil in pregnancy on infant cognitive development or growth at 1 y of age (Helland et al, 2001). Clearly, longer-term studies of the potential effects on a variety of health-related outcomes are required. Furthermore, the significance of the concomitant decrease in AA status requires further investigation. These issues need to be addressed, particularly in view of the growing public enthusiasm for fish oil supplementation, and the addition of n-3 PUFA to many foodstuffs.

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Acknowledgements

We wish to acknowledge the staff and patients who assisted us in this study. We are particularly grateful to the obstetricians and midwives at St John of God Hospital, Subiaco, Western Australia. We thank Professor Scott Weiss, Harvard Medical School for his role in the planning and design of this study. We also wish to thank Ms Lynette McCahon for technical assistance, Ms Elaine Pascoe for statistical advice and Dr Thierry Venaille for his advice and support during the study design. The study was supported by grants from the NH & MRC and Raine Medical Research Foundation, Australia.

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Guarantor: SL Prescott was accountable for all parts of the completed manuscript before and after publication.

Contributors J A Dunstan—study design, collection and analysis of data, writing the manuscript. T A Mori, Anne Barden, Lawrie Beilin—study design, collection of data, writing the manuscript. P G Holt—significant advice and consultation on study design; significant consultation on collection of data. P Calder—significant advice and consultation on study design; writing the manuscript. A L Taylor—collection of data. S L Prescott—senior author responsible for study design; collection and analysis of data; writing the manuscript.

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Correspondence to S L Prescott.

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Dunstan, J., Mori, T., Barden, A. et al. Effects of n-3 polyunsaturated fatty acid supplementation in pregnancy on maternal and fetal erythrocyte fatty acid composition. Eur J Clin Nutr 58, 429–437 (2004). https://doi.org/10.1038/sj.ejcn.1601825

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Keywords

  • PUFA
  • n-3 fatty acids
  • docosahexaenoic acid
  • arachidonic acid
  • fish oil
  • pregnancy
  • atopy

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