MP Freeman. Omega-3 fatty acids in psychiatry: a review. Ann Clin Psychiatry 2000;12(3):159-165

Omega-3 fatty acids are long-chain, polyunsaturated fatty acids found in plant and marine sources. Unlike saturated fats, which have been shown to have negative health consequences, omega-3 fatty acids are polyunsaturated fatty acids that have been associated with many health benefits.

Omega-3 fatty acids may prove to be efficacious in a number of psychiatric disorders.

Mood disorders have been associated with abnormalities in fatty acid composition. Several lines of evidence suggest that diminished omega-3 fatty acid concentrations are associated with mood disorders.

Clinical data are not yet available regarding omega-3 fatty acids in the treatment of major depression. However, one double-blind treatment trial has been conducted in bipolar disorder. Also, substantial evidence does exist supporting a potential role of omega-3 fatty acids in schizophrenia, although treatment data are needed.

A case has been reported in which a patient with schizophrenia was successfully treated with omega-3 fatty acids. Controlled studies are necessary to explore the potential treatment of schizophrenia with omega-3 fatty acids. Omega-3 fatty acids may also be helpful in the treatment of dementia.

Furthermore, omega-3 fatty acids may prove to be a safe and efficacious treatment for psychiatric disorders in pregnancy and in breastfeeding.

Min Y, Lowy C, Ghebremeskel K, et al. Unfavorable effect of type 1 and type 2 diabetes on maternal and fetal essential fatty acid status: a potential marker of fetal insulin resistance. Am J Clinical Nutrition, 2005; 82 (6):1162-1168.

Background:
Pregestational maternal diabetes increases obesity and diabetes risks in the offspring. Both conditions are characterized by insulin resistance, and diabetes is associated with low membrane arachidonic (AA) and docosahexaenoic (DHA) acids.

Objective:
We investigated whether type 1 and type 2 diabetes in pregnancy compromise maternal and fetal membrane essential fatty acids (FAs).

Design:
We studied 39 nondiabetic (control subjects), 32 type 1 diabetic, and 17 type 2 diabetic pregnant women and the infants they delivered. Maternal and cord blood samples were obtained at midgestation and at delivery, respectively. Plasma triacylglycerols and choline phosphoglycerides and red blood cell (RBC) choline and ethanolamine phosphoglyceride FAs were assessed.

Results:
The difference in maternal plasma triacylglycerol FAs between groups was not significant.
However, the type 1 diabetes group had lower plasma choline phosphoglyceride DHA (3.7 ± 0.9%; P < 0.01) than did the control group (5.2 ± 1.6%).
Likewise, RBC DHA was lower in the type 1 [choline: 3.4 ± 1.5% (P < 0.01); ethanolamine: 5.9 ± 2.5% (P < 0.05)] and type 2 [choline: 3.5 ± 1.6% (P < 0.05)] diabetes groups than in the control group (choline: 5.5 ± 2.2%; ethanolamine: 7.5 ± 2.5%).

Cord AA and DHA were lower in the plasma (type 1: P < 0.01) and RBC (type 2: P < 0.05) choline phosphoglycerides of the diabetics than of the control subjects, and cord RBC ethanolamine phosphoglycerides were lower in DHA (P < 0.05) in both diabetes groups than in the control group.

Conclusions:
Diabetes (either type) compromises maternal RBC DHA and cord plasma and RBC AA and DHA. The association of these 2 FAs with insulin sensitivity may mean that the current finding explains the higher incidence of insulin resistance and diabetes in the offspring of diabetic women.

Otto SJ, van Houwelingen AC, Badart-Smook A, et al. Comparison of the peripartum and postpartum phospholipid polyunsaturated fatty acid profiles of lactating and non-lactating women. Am J Clin Nutr 2001 Jun;73(6):1074-1079.

BACKGROUND: Pregnancy is associated with increased absolute amounts of docosahexaenoic acid (DHA; 22:6n-3) in plasma phospholipids. Expressed as a proportion of total fatty acids, DHA declines slightly in late pregnancy but little information is available on the normalization of DHA postpartum, which may be different in lactating and nonlactating women.

OBJECTIVE: The aim was to investigate maternal plasma and erythrocyte long-chain polyunsaturated fatty acids (long-chain polyenes; LCPs) postpartum, particularly DHA, in relation to lactation and dietary LCP intake.

DESIGN: Healthy pregnant women who intended to breast-feed or exclusively bottle-feed their infants were studied at 36-37 wk of pregnancy. Blood samples were collected at entry, after parturition on days 2 and 5, and 1, 2, 4, 8, 16, 32, and 64 wk postpartum. Fatty acid profiles were analyzed in plasma and erythrocyte phospholipids. Dietary intakes were assessed 4 and 32 wk postpartum with a validated food-frequency questionnaire.

RESULTS: After delivery, the percentages of plasma linoleic, arachidonic, eicosapentaenoic, and docosapentaenoic acids increased over time, whereas the percentage of docosapentaenoic acid decreased; the patterns of change did not differ significantly between the lactating and nonlactating groups. The percentage of DHA in plasma and erythrocyte phospholipid fatty acids declined significantly in the 2 groups, more so in the lactating women, and was enhanced when the lactation period was extended. Despite the apparent higher dietary intake of essential fatty acids in the lactating group at week 4, it was not significantly different from that of the nonlactating group.

CONCLUSION: Normalization of maternal plasma and erythrocyte phospholipid n-3 LCPs differs significantly between lactating and nonlactating women postpartum but that of n-6 LCPs does not.

PMID: 11382662

Francois CA, Connor SL, et al. Supplementing lactating women with flaxseed oil does not increase docosahexaenoic acid in their milk. American Journal of Clinical Nutrition, 2003; 77 (1): 226-233

Background: Flaxseed oil is a rich source of 18:3n-3 (alpha-linolenic acid, or ALA), which is ultimately converted to 22:6n-3 (docosahexaenoic acid, or DHA), a fatty acid important for the development of the infant brain and retina.

Objective: The objective of this study was to determine the effect of flaxseed oil supplementation on the breast-milk, plasma, and erythrocyte contents of DHA and other n-3 fatty acids in lactating women.

Design: Seven women took 20 g flaxseed oil (10.7 g ALA) daily for 4 wk. Breast-milk and blood samples were collected weekly before, during, and after supplementation and were analyzed for fatty acid composition.

Results: Breast milk, plasma, and erythrocyte ALA increased significantly over time (P < 0.001) and after 2 and 4 wk of supplementation (P < 0.05). Over time, 20:5n-3 (eicosapentaenoic acid, or EPA) increased significantly in breast milk (P = 0.004) and in plasma (P < 0.001). In addition, plasma EPA increased significantly (P < 0.05) after 2 and 4 wk of supplementation. There were significant increases over time in breast-milk 22:5n-3 (docosapentaenoic acid, or DPA) (P < 0.02), plasma DPA (P < 0.001), and erythrocyte DPA (P < 0.01). No significant changes were observed in breast-milk, plasma, or erythrocyte DHA contents after flaxseed oil supplementation.

Conclusions: Dietary flaxseed oil increased the breast-milk, plasma, and erythrocyte contents of the n-3 fatty acids ALA, EPA, and DPA but had no effect on breast-milk, plasma, or erythrocyte DHA contents.

Gerard Hornstra. Essential fatty acids in mothers and their neonates. Am J Clin Nutr, 2000;71(5):1262S-1269S.

Essential fatty acids (EFAs) and their long-chain polyenes (LCPs) are indispensable for human development and health. Because humans cannot synthesize EFAs and can only ineffectively synthesize LCPs, EFAs need to be consumed as part of the diet.

Consequently, the polyunsaturated fatty acid (PUFA) status of the developing fetus depends on that of its mother, as confirmed by the positive relation between maternal PUFA consumption and neonatal PUFA status.

Pregnancy is associated with a decrease in the biochemical PUFA status, and normalization after delivery is slow. This is particularly true for docosahexaenoic acid (DHA) because, on the basis of the current habitual diet, birth spacing appeared to be insufficient for the maternal DHA status to normalize completely.

Because of the decrease in PUFA status during pregnancy, the neonatal PUFA status may not be optimal. This view is supported by the lower neonatal PUFA status after multiple than after single births.

The neonatal PUFA status can be increased by maternal PUFA supplementation during pregnancy. For optimum results, the supplement should contain both n-6 and n-3 PUFAs.

The PUFA status of preterm neonates is significantly lower than that of term infants, which is a physiologic condition. Because the neonatal DHA status correlates positively with birth weight, birth length, and head circumference, maternal DHA supplementation during pregnancy may improve the prognosis of preterm infants.

In term neonates, maternal linoleic acid consumption correlates negatively with neonatal head circumference. This suggests that the ratio of n-3 to n-6 PUFAs in the maternal diet should be increased.

Consumption of trans unsaturated fatty acids appeared to be associated with lower maternal and neonatal PUFA status. Therefore, it seems prudent to minimize the consumption of trans fatty acids during pregnancy.

Makrides M, Gibson R. Long-chain polyunsaturated fatty acid requirements during pregnancy and lactation. Am J Clin Nutr 2000;71:307-311.

Much interest has been expressed about the long-chain polyunsaturated fatty acid (LCPUFA) requirements of both preterm and term infants, whereas relatively little attention has been given to the LCPUFA needs of mothers, who may provide the primary source of LCPUFAs for their fetuses and breast-fed infants.

Although maternal requirements for LCPUFAs are difficult to estimate because of large body stores and the capacity to synthesize LCPUFAs from precursors, biochemical and clinical intervention studies have provided some clues. From a biochemical viewpoint, there appears to be no detectable reduction in plasma n-3 LCPUFA concentrations during pregnancy, whereas there is a clear decline during the early postpartum period.

The postpartum decrease in maternal plasma docosahexaenoic acid (DHA) concentration is not instantaneous, may be long-term, is independent of lactation, and is reversible with dietary DHA supplementation (200-400 mg/d). From a functional standpoint, the results of randomized clinical studies suggest that n-3 LCPUFA supplementation during pregnancy does not affect the incidences of pregnancy-induced hypertension and preeclampsia without edema. However, n-3 LCPUFA supplementation may cause modest increases in the duration of gestation, birth weight, or both.

To date, there is little evidence of harm as a result of n-3 LCPUFA supplementation during either pregnancy or lactation. However, researchers need to further elucidate any potential benefits of supplementation for mothers and infants. Careful attention should be paid to study design, measurement of appropriate health outcomes, and defining minimum and maximum plasma n-3 LCPUFA concentrations that are optimal for both mothers and infants.

PMID: 10617987

Crawford MA. Placental delivery of arachidonic and docosahexaenoic acids: implications for the lipid nutrition of preterm infants. American Journal of Clinical Nutrition, 2000;71(1):275-284

Arachidonic (AA) and docosahexaenoic (DHA) acids are major components of cell membranes and are of special importance to the brain and blood vessels. In utero, the placenta selectively and substantially extracts AA and DHA from the mother and enriches the fetal circulation.

Studies indicate that there is little placental conversion of the parent essential fatty acids to AA and DHA. Similarly, analyses of desaturation and reductase activity have shown the placenta to be less functional than the maternal or fetal livers. There appears to be a correlation with placental size and plasma AA and DHA proportions in cord blood; therefore, placental development may be an important variable in determining nutrient transfer to the fetus and, hence, fetal growth itself.

In preterm infants, both parenteral and enteral feeding methods are modeled on term breast milk. Consequently, there is a rapid decline of the plasma proportions of AA and DHA to one quarter or one third of the intrauterine amounts that would have been delivered by the placenta. Simultaneously, the proportion of linoleic acid, the precursor for AA, rises in the plasma phosphoglycerides 3-fold.

An inadequate supply of AA and DHA during the period of high demand from rapid vascular and brain growth could lead to fragility, leakage, and membrane breakdown. Such breakdown would predictably be followed by peroxidation of free AA, vasoconstriction, inflammation, and ischemia with its biological sequelae. In the brain, cell death would be an extreme consequence.

SL Brooks, A Mitchell, and N Steffenson. Mothers, infants, and DHA. Implications for nursing practice. MCN Am J Matern Child Nurs, 2000;25(2):71-75

The purpose of this article is to describe the professional literature and current controversies concerning the relationship between essential fatty acids, especially Docohexaenoic Acid (DHA), and neurologic function.

Although there is debate in the literature concerning just how much DHA is required for optimal neurologic functioning of infants, it is known that adequate DHA levels are dependent on an adequate dietary intake.

However, common dietary practices today may not provide enough DHA.

Because pregnancy and lactation are key times of rapid brain growth for the developing fetus and infant, nurses can be instrumental in teaching pregnant and lactating women diet-related information and promoting practices that help increase DHA levels. By understanding the importance of DHA in pregnancy and infancy, the nurse can take a more active role in essential health education.

Cohen JT, Bellinger DC, Connor WE, Shaywitz BA. A quantitative analysis of prenatal intake of n-3 polyunsaturated fatty acids and cognitive development. Am J Prev Med, 2005;29(4):366-374.

Although a rich source of n-3 polyunsaturated fatty acids (PUFAs) that may confer multiple health benefits, some fish also contain methyl mercury (MeHg), which may harm the developing fetus.

U.S. government recommendations for women of childbearing age are to modify consumption of high-MeHg fish to reduce MeHg exposure, while recommendations encourage fish consumption among the general population because of the nutritional benefits. The Harvard Center for Risk Analysis convened an expert panel (see acknowledgements) to quantify the net impact of resulting hypothetical changes in fish consumption across the population.

This paper estimates the impact of prenatal n-3 intake on cognitive development. Other papers quantify the negative impact of prenatal exposure to MeHg on cognitive development, and the extent to which fish consumption protects against coronary heart disease mortality and stroke in adults.

This paper aggregates eight randomized controlled trials (RCTs) comparing cognitive development in controls and in children who had received n-3 PUFA supplementation (seven studies of formula supplementation and one study of maternal dietary supplementation).

Our analysis assigns study weights accounting for statistical precision, relevance of three endpoint domains (general intelligence, verbal ability, and motor skills) to prediction of IQ, and age at evaluation.

The study estimates that increasing maternal docosahexaenoic acid (DHA) intake by 100 mg/day increases child IQ by 0.13 points. The paper notes that findings were inconsistent across the RCTs evaluated (although our findings were relatively robust to changes in the weighting scheme used). Also, for seven of the eight studies reviewed, effects are extrapolated from formula supplementation to maternal dietary intake.

Olafsdottir A, Wagner K, et al. Fat-soluble vitamins in the maternal diet, influence of cod liver oil supplementation and impact of the maternal diet on human milk composition. Ann Nutr Metab 2001;45(6):265-72.

BACKGROUND/AIMS: To investigate lactating mothers' intake of fat-soluble vitamins in free-living subjects and to what extent cod liver oil supplementation influences the maternal intake in a population with common intake of cod liver oil. The impact of maternal diet on the concentration of fat-soluble vitamins in human milk was studied.

METHODS: Dietary intake of 77 lactating women was investigated by 24-hour diet recalls and breast-milk samples were taken at the same occasions. Breast milk samples were analyzed for fat-soluble vitamins.

RESULTS: The median intakes were 927 microg/day for vitamin A, 5.5 mg/day for vitamin E and 3.3 microg/day for vitamin D. Maternal vitamin A, E and D intakes were higher when the diet was supplemented with cod liver oil. Icelandic breast milk was found to have high contents of vitamin A and E. Only vitamin D was too low in breast milk to meet the recommended intake for infants. Retinylpalmitate in relation to lipids correlated with maternal vitamin A intake (r = 0.23, p < 0.05). The group with cod liver oil supplementation had significantly lower levels of gamma-tocopherol in breast milk (p < 0.01), whereas the supplementation did not affect other fat-soluble vitamins.

CONCLUSION: The recommended intake of fat-soluble vitamins for lactating women can more easily be met with a cod liver oil supplementation than diet alone. Only vitamin D in human milk cannot meet the recommended intakes for infants, with normal breastfeeding. There is a relationship between the content of vitamins A and E in human milk and the maternal diet.

Freeman M, Hibbeln J, Wisner K, et al. An open trial of Omega-3 fatty acids for depression in pregnancy . Acta Neuropsychiatrica 2006;18(1):21-24.

Objective: In this flexible-dose, open-label trial, we examined the efficacy of omega-3 fatty acids for the treatment of depression during pregnancy.

Methods: Fifteen pregnant women with major depressive episodes participated. Subjects initially received two capsules per day [0.93 g of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)]; the dose could be increased by one capsule per day every 2 weeks to a maximal dose of 2.8 g.
Subjects were assessed with the Edinburgh Postnatal Depression Scale (EPDS) and Hamilton Rating Scale for Depression (HRSD).

Results: Average duration of participation in this treatment trial was 8.3 weeks (SD +/- 7.1). Average final dose of EPA + DHA in this flexible dose trial was 1.9 g per day (+/-0.5). The mean reduction in EPDS scores was 40.9% (SD +/- 21.9); the mean decrease in HRSD score was 34.1% (SD +/- 27.1).

Conclusions: This open trial provides data to support the need for randomized controlled dose-finding trials of omega-3 fatty acids in major depressive episodes during pregnancy.

Freeman MP, Hibbeln JR, Wisner KL, et al. Randomized dose-ranging pilot trial of omega-3 fatty acids for postpartum depression. Acta Psychiatr Scand, 2005; 0 (0):1?5. Online Early doi:10.1111/j.1600-0447.2005.00660.x

Objective: Postpartum depression (PPD) affects 10?15% of mothers. Omega-3 fatty acids are an intriguing potential treatment for PPD.

Method: The efficacy of omega-3 fatty acids for PPD was assessed in an 8-week dose-ranging trial. Subjects were randomized to 0.5 g/day (n = 6), 1.4 g/day (n = 3), or 2.8 g/day (n = 7).

Results: Across groups, pretreatment Edinburgh Postnatal Depression Scale (EPDS) and Hamilton Rating Scale for Depression (HRSD) mean scores were 18.1 and 19.1 respectively; post-treatment mean scores were 9.3 and 10.0.

Percent decreases on the EPDS and HRSD were 51.5% and 48.8%, respectively; changes from baseline were significant within each group and when combining groups. Groups did not significantly differ in pre- or post-test scores, or change in scores.

The treatment was well tolerated.

Conclusion: This study was limited by small sample size and lack of placebo group. However, these results support further study of omega-3 fatty acids as a treatment for PPD.

Al MD, van Houwelingen AC, Kester AD, et al. Maternal essential fatty acid patterns during normal pregnancy and their relationship to the neonatal essential fatty acid status. Br J Nutr 1995 Jul;74(1):55-68.

Although essential fatty acids (EFA) and their longer chain, more unsaturated derivatives play a major role during pregnancy, hardly any information is available with respect to the course of the maternal EFA status during an uncomplicated pregnancy and its relationship to the neonatal EFA status. Therefore, a longitudinal study was started in which 110 pregnant women gave repeated blood samples from the 10th week of gestation until delivery.

After birth a blood sample from the umbilical vein and a maternal venous blood sample were collected as well, and 6 months after delivery a final blood sample from the mother was taken. The absolute (mg/l) and relative (% total fatty acids) amounts of the fatty acids in plasma phospholipids were determined.

The total amounts of fatty acids increased significantly during pregnancy. This pattern was similar for the individual fatty acids and fatty acid families. The relative amount of linoleic acid (18:2n-6) did not change during pregnancy, whereas the relative amount of arachidonic acid (20:4n-6) decreased. Despite maternal mobilization of docosahexaenoic acid (22:6n-3, DHA), suggested by a temporary increase in the DHA status until 18 weeks gestation, the DHA status steadily declined thereafter.

This pattern was associated with a progressive increase in the DHA deficiency index in maternal blood throughout pregnancy and resulted in a sub-optimal neonatal DHA status. The overall maternal EFA status also declined steadily during pregnancy. Therefore, the question arises whether the mother, under the prevailing dietary conditions, is able to meet the high fetal requirement for EFA.

PMID: 7547829

Olafsdottir AS, Magnusardottir AR, et al. Relationship between dietary intake of cod liver oil in early pregnancy and birthweight. BJOG, 2005; 112(4):424-429

OBJECTIVE: To investigate the possible association between birth outcome and marine food and cod liver oil intake of healthy women in early (prior to 15 weeks of gestation) pregnancy.

DESIGN: An observational study.

SETTING: Free-living conditions in a community with traditional fish and cod liver oil consumption.

POPULATION: Four hundred and thirty-five healthy pregnant Icelandic women without antenatal and intrapartum complications.

METHODS: Dietary intake of the women was estimated with a semi-quantitative food frequency questionnaire (FFQ) covering food intake together with lifestyle factors for the previous three months. Questionnaires were filled out at between 11 and 15 weeks and between 34 and 37 weeks of gestation. The estimated intake of marine food and cod liver oil was compared with birthweight by linear and logistic regression controlling for potential confounding.

MAIN OUTCOME MEASURES: Birthweight, cod liver oil intake, lifestyle factors (alcohol, smoking).

RESULTS: Fourteen percent of the study population used liquid cod liver oil in early pregnancy. Regression analysis shows that these women gave birth to heavier babies (P < 0.001), even after adjusting for the length of gestation and other confounding.

CONCLUSIONS: Maternal intake of liquid cod liver oil early in pregnancy was associated with a higher birthweight.

Higher birthweight has been associated with a lower risk of diseases later in life and maternal cod liver oil intake might be one of the means for achieving higher birthweight.

Dunstan JA, Mori TA, et al. Maternal fish oil supplementation in pregnancy reduces interleukin-13 levels in cord blood of infants at high risk of atopy. Clin Exp Allergy, 2003;33(4):442-448

BACKGROUND AND OBJECTIVES: The epidemiological association between higher dietary n-3 polyunsaturated fatty acids (PUFA) and lower prevalence of asthma, has led to interest in the role of early dietary modification in allergic disease prevention.

In this study we examined the effects of maternal n-3 (PUFA)-rich fish oil supplementation on cord blood (CB) IgE and cytokine levels in neonates at risk of developing allergic disease.

METHODS: In a randomized double-blind, placebo-controlled trial, 83 atopic pregnant women received either fish oil capsules (n = 40) containing 3.7 g n-3 PUFA/day or placebo capsules (n = 43) from 20 weeks gestation until delivery. CB cytokine levels (IL-4, IL-5, IL-6, IL-10, IL-12, IL-13, TNF-alpha and IFN-gamma) and total IgE levels were measured and compared between the two groups.
Fatty acid composition of red cell membranes was analysed by gas chromatography and the relationships among PUFA, cytokine and IgE levels were examined.

RESULTS: Maternal fish oil supplementation resulted in a significant increase in n-3 PUFA levels (P < 0.001) in neonatal erythrocyte membranes.

Neonates whose mothers had fish oil supplementation had significantly lower plasma IL-13 (P < 0.05) compared to the control group.
There was also a significant inverse relationship between levels of n-3 PUFA in neonatal cell membranes and plasma IL-13. There was no difference in levels of IgE and the other cytokines measured.

CONCLUSIONS: This study provides preliminary evidence that increasing neonatal n-3 PUFA levels with maternal dietary supplementation can achieve subtle modification of neonatal cytokine levels.

Further assessment of immune function and clinical follow-up of these infants will help determine if there are any significant effects on postnatal immune development and expression of allergic disease.

PMID: 12680858

Dunstan J, Roper J, et al. The effect of supplementation with fish oil during pregnancy on breast milk immunoglobulin A, soluble CD14, cytokine levels and fatty acid composition. Clin Exp Allergy, 2004;34(8):1237-1242

BACKGROUND: Breast milk contains many immunomodulatory factors (soluble CD14 (sCD14), IgA and cytokines) with the potential to influence infant immune development.

OBJECTIVE: To determine if changes in breast milk omega-3 polyunsaturated fatty acid (n-3 PUFA) composition as a result of maternal dietary fish oil supplementation during pregnancy can modify levels of these immunological parameters in breast milk.

METHOD: In a randomized controlled trial, 83 atopic women received either 4 g fish oil capsules (containing 3.7 g n-3 PUFA) (n = 40) or 4 g olive oil capsules (n = 43) from 20 weeks gestation until delivery. Breast milk was collected 3 days post-partum and fatty acids were analysed by gas liquid chromatography and IgA, sCD14 and cytokines (IL-5, IL-6, IL-10, TNF-alpha and IFN-gamma) were quantitated by ELISA or time resolved fluorescence (TRF).

RESULTS: Omega-3 docosahexaenoic acid (DHA; 22:6n-3) and eicosapentaenoic acid (EPA; 20:5n-3) levels were significantly higher (P < 0.001) in breast milk from women supplemented with fish oil (n = 33, DHA mean 1.15%, SD 0.47% and EPA mean 0.16%, SD 0.07%) than in samples from the control group (n = 40, DHA mean 0.50%, SD 0.17% and EPA mean 0.05%, SD 0.02%). Breast milk arachidonic acid (AA; 20:4n-6) levels were significantly lower (P = 0.045) in the fish oil group (mean 0.55%, SD 0.12%) compared with the control group (mean 0.61%, SD 0.14%).

Breast milk IgA was positively correlated with DHA (P = 0.046) and 22:5n-3 (P = 0.003), but inversely correlated with linoleic acid (LA; 18:2n-6) (P=0.034). Levels of sCD14 were also positively correlated with 22:5n-3 (P=0.009). Cytokines involved in IgA synthesis (IL-10 and IL-6) were also significantly correlated with both IgA and n-3 PUFA levels, although there were no differences in the levels of breast milk IgA, sCD14 or cytokines between study groups.

CONCLUSION: Supplementation with fish oil during pregnancy significantly alters early post-partum breast milk fatty acid composition. omega-3 PUFA levels were positively associated with IgA and sCD14 levels, suggesting a relationship between fatty acid status and mucosal immune function.

SJ Otto, RH de Groot, and G Hornstra. Increased risk of postpartum depressive symptoms is associated with slower normalization after pregnancy of the functional docosahexaenoic acid status.
Prostaglandins Leukot Essent Fatty Acids,2003;69(4):237-243

Observational studies suggest an association between a low docosahexaenoic acid (DHA, 22:6n-3) status after pregnancy and the occurrence of postpartum depression. However, a comparison of the actual biochemical plasma DHA status among women with and without postpartum depression has not been reported yet.

The contents of DHA and of its status indicator n-6 docosapentaenoic acid (n-6DPA, 22:5n-6) were measured in the plasma phospholipids of 112 women at delivery and 32 weeks postpartum. At this latter time point, the Edinburgh Postnatal Depression Scale (EPDS) questionnaire was completed to measure postpartum depression retrospectively.

The EPDS cutoff score of 10 was used to define 'possibly depressed' (EPDS score > or =10) and non-depressed women (EPDS score <10). Odds ratios (OR) were calculated using a multiple logistic regression analysis with the EPDS cutoff score as dependent and fatty acid concentrations and ratio's as explanatory variables, while controlling for different covariables.

The results demonstrated that the postpartum increase of the functional DHA status, expressed as the ratio DHA/n-6DPA, was significantly lower in the 'possibly depressed' group compared to the non-depressed group (2.34+/-5.56 versus 4.86+/-5.41, respectively; OR=0.88, P=0.03). Lactating women were not more predisposed than non-lactating women were to develop depressive symptoms.

From this observation it seems that the availability of DHA in the postpartum period is less in women developing depressive symptoms. Although further studies are needed for confirmation, increasing the dietary DHA intake during pregnancy and postpartum, seems prudent.

Stene LC, Ulriksen J, et al. Use of cod liver oil during pregnancy associated with lower risk of Type I diabetes in the offspring. Diabetologia, 2000;43(9):1093-1098

AIMS/HYPOTHESIS: To test whether cod liver oil or vitamin D supplements either taken by the mother during pregnancy or by the child in the first year of life is associated with lower risk of Type I (insulin-dependent) diabetes mellitus in children.

METHODS: We carried out a population-based case control study in Vest-Agder county of Norway, evaluating the use of supplements by a mailed questionnaire. We received responses from 85 diabetic subjects and 1,071 control subjects. Odds ratios (OR) with 95% confidence intervals (CI) were estimated using logistic regression analyses.

RESULTS: When mothers took cod liver oil during pregnancy their offspring had a lower risk of diabetes. The unadjusted OR was 0.30, 95% CI: (0.12 to 0.75), p = 0.01. This association changed very little and was still significant after adjusting for age, sex, breastfeeding and maternal education. Mothers taking multivitamin supplements during pregnancy [adjusted OR= 1.11, 95% CI: (0.69 to 1.77)], infants taking cod liver oil in the first year of life [adjusted OR = 0.82, 95 % CI: (0.47 to 1.42) and the use of other vitamin D supplements in the first year of life [adjusted OR = 1.27, 95 % CI: (0.70 to 2.31)] was not [corrected] significantly associated with the risk of diabetes.

CONCLUSION/INTERPRETATION: We found that cod liver oil taken during pregnancy was associated with reduced risk of Type I diabetes in the offspring. This suggests that vitamin D or the n-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid in the cod liver oil, or both, have a protective effect against Type I diabetes.

Moms and Mercury by Ernie Hood. Fine-Tuning Fish Consumption During Pregnancy. Environmental Health Perspectives, 2005;113:1376-1380.

EHP is a monthly journal of peer-reviewed research and news on the impact of the environment on human health.

Due to ongoing concerns that high mercury intake via fish can cause adverse neurologic effects in the developing fetus, the U.S. Food and Drug Administration now recommends that expectant mothers should limit their consumption of fish to two or fewer meals per week. But pregnant women shouldn't throw the baby out with the bathwater.

A new study by a group of Harvard researchers suggests that this advice, which could result in many pregnant women eliminating fish from their diets altogether, may be denying some babies substantial neurocognitive benefits gained from important nutrients found in fish, such as n-3 polyunsaturated fatty acids.

The scientists sought to determine whether fish consumption during pregnancy is harmful or beneficial to fetal brain development.
To do this, they examined associations of maternal fish consumption during pregnancy, maternal hair mercury levels (a sensitive marker of organic mercury body burden) at delivery, and infant cognition at age 6 months. Study subjects were 135 mother-infant pairs who participated in Project Viva, a prospective pregnancy and child health cohort study in eastern Massachusetts.

The mothers completed questionnaires about fish consumption during their second trimester. That period of time was used to best coordinate temporally with the mercury exposure reflected in maternal hair samples, which were taken at delivery. The questions concerned how much and what categories of fish (canned tuna, dark meat, light meat, shellfish) the women ate.

Mothers consumed an average of 1.2 servings of combined fish categories per week. Their mean hair mercury level was 0.55 part per million (ppm), with 10% of the samples higher than 1.2 ppm, the current U.S. reference dose. Fish consumption was directly correlated with hair mercury levels.

Infant cognition was assessed using a test called visual recognition memory (VRM). In the VRM test, which has been shown to correlate with later IQ, the child is first shown two identical photographs of an infant's face, side by side, at a standardized distance. Then, one of the photos is replaced with a photo of another infant's face.
By tracking the percentage of time the baby looks at each photo, a novelty preference score is derived, reflecting the infant's ability to encode a stimulus into memory, to recognize that stimulus, and to look preferentially at a novel stimulus.

Mean VRM score among the children was 59.8, with a range of 10.9-92.5. After accounting for characteristics such as maternal age and education level, higher fish intake was found to be associated with higher infant cognition, especially after adjusting for mercury levels, which had a dose-dependent negative impact on the infants' cognition.
For each additional weekly serving of fish, the infants' VRM score was 4.0 points higher. Conversely, the researchers found that an increase of 1 ppm in hair mercury was associated with a decrement in VRM score of 7.5 points.

The babies with the highest cognition scores were from mothers who had eaten more than two weekly fish servings but had mercury levels of 1.2 ppm or less.

Although the results may seem contradictory, the authors suggest that the most cognitive benefit is derived by mothers eating fish types with the combination of relatively little mercury and high amounts of beneficial nutrients.
However, since the study assessed maternal fish consumption of four broad categories, there is no information presented on associations with specific types of fish. The researchers say that future studies could incorporate more detailed dietary information to help pregnant women make informed decisions about which fish meals are better or worse for their children's cognition.

Ultimately, the message behind these findings is that pregnant women should continue to eat fish, but should try to choose varieties known to be low in mercury and high in nutrients, such as canned light tuna and sardines.
Finding the most appropriate balance between risk and benefit may be challenging in this situation, but given the strong associations found in the current study, making the right decisions about which fish to eat during pregnancy, and how often, may be even more important than previously suspected.

Helland IB, Saarem K, Saugstad OD, et al. Fatty acid composition in maternal milk and plasma during supplementation with cod liver oil. Eur J Clin Nutr 1998;52:839-845.

OBJECTIVE: We investigated how cod liver oil influences the amount of essential fatty acids in mothers' breast milk.

DESIGN AND INTERVENTION: Lactating mothers (n =22) were randomized into four groups 3-8 weeks after parturition. They were supplemented for 14 days with 0, 2.5, 5 and 10 ml cod liver oil (7.7 g eicosapentaenoic acid (EPA, 20:5n-3), 10.2 g docosahexaenoic acid (DHA, 22:6n-3) and 22.9 g n-3 fatty acids in total per 100 ml.

RESULTS: In maternal plasma phospholipids there was an increase in the content of EPA and DHA in the group supplemented with 10 ml cod liver oil daily (P < or = 0.05). DHA concentrations in breast milk pre-supplementation ranged from 0.15 to 1.56 wt% and increased in all supplemented groups (P< or =0.05). The concentration of EPA in breast milk increased in the groups supplemented with 5 or 10 ml cod liver oil (P< or =0.05), whereas the concentration of arachidonic acid (AA, 20:4n-6) did not change in any of the supplemented groups. Total intake of DHA adjusted to body mass index (BMI), correlated to DHA concentrations in plasma (r = 0.49, P = 0.02) and breast milk (r = 0.45, P = 0.04). The concentration of tocopherol did not change during the supplementation period, neither in plasma nor in breast milk.

CONCLUSION: Dietary intake of DHA is reflected in the concentration of DHA in breast milk, without affecting the concentration of AA or tocopherol.

PMID: 9846598

Dunstan J, Mori T, et al. Effects of n-3 polyunsaturated fatty acid supplementation in pregnancy on maternal and fetal erythrocyte fatty acid composition. Eur J Clin Nutr 2004;58(3:429-437

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.

INTERVENTION: 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.

CONCLUSION: 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.

MG Weisskopf, HA Anderson, LP Hanrahan, and Great Lakes Consortium.
Decreased sex ratio following maternal exposure to polychlorinated biphenyls from contaminated Great Lakes sport-caught fish: a retrospective cohort study. Environ Health,2003;2(1):

Background

Fish from the Great Lakes are contaminated with polychlorinated biphenyls, which have been found to have several adverse reproductive effects. Several environmental contaminants have been found to alter the sex ratio of offspring at birth, but the evidence of such an effect of polychlorinated biphenyls has been inconsistent.

Methods

We examined parental serum polychlorinated biphenyl concentration in relation to the sex ratio of 173 children of mothers and 208 children of fathers from the Great Lakes region of the United States between 1970 and 1995. We calculated odds ratios for a male child using logistic regression and generalized estimating equations with adjustment for the year of birth of the child, maternal and paternal age, the mother's parity at the child's birth, and whether the child had an older brother.

Results

The adjusted odds ratio for having a male child among mothers in the highest quintile of serum polychlorinated biphenyl concentration was 0.18 (95% CI: 0.06-0.59) compared to mothers in the lowest quintile. Treating exposure as a continuous variable, the adjusted odds ratio for having a male child was 0.54 per unit increase in the natural log of maternal serum polychlorinated biphenyl concentration (95% CI: 0.33-0.89). There was little evidence of an association with paternal exposure. We found no association between either maternal or paternal serum dichlorodiphenyl-dichloroethene concentration and the sex ratio.

Conclusions

These findings suggest that maternal exposure to polychlorinated biphenyls may decrease the sex ratio of offspring. These data

Williams MA, Zingheim RW, King IB, Zebelman AM; Omega-3 fatty acids in maternal erythrocytes and risk of preeclampsia; Epidemiology 1995;6(3):232-237.

Preeclampsia is a systemic disease characterized by diffuse endothelial dysfunction, increased peripheral vascular resistance, coagulation abnormalities, antioxidant deficiency, persistent elevations of maternal leukocyte-derived cytokines, and hyperlipidemia.

Fish oil, rich in omega-3 polyunsaturated fatty acids, is known to reduce fasting and postprandial triglycerides and to decrease platelet and leukocyte reactivity; it may also decrease blood pressure.

Additionally, omega-3 fatty acids may beneficially influence vessel wall characteristics and blood rheology.

In light of the potential beneficial effects of dietary omega-3 fatty acids, we conducted a cross-sectional case-control study to examine the hypothesized exposure-effect relation between maternal dietary intake of marine omega-3 fatty acids and risk of preeclampsia.

We measured polyunsaturated fatty acids in erythrocytes obtained from 22 preeclamptic women and 40 normotensive women; we measured polyunsaturated fatty acids as the percentage of total fatty acids from gas chromatography.

We employed logistic regression procedures to estimate odds ratios (ORs) and 95% confidence intervals (CIs).

After adjusting for confounders, women with the lowest levels of omega-3 fatty acids were 7.6 times more likely to have had their pregnancies complicated by preeclampsia as compared with those women with the highest levels of omega-3 fatty acids (95% CI = 1.4-40.6).

A 15% increase in the ratio of omega-3 to omega-6 fatty acids was associated with a 46% reduction in risk of preeclampsia (OR = 0.54; 95% CI = 0.41-0.72).

Low erythrocyte levels of omega-3 fatty acids and high levels of some omega-6 fatty acids, particularly arachidonic acid, appear to be associated with an increased risk of preeclampsia.

Singh M. Essential fatty acids, DHA and human brain.
Indian J Pediatr,2005;72(3):239-242

Essential fatty acids cannot be synthesized in the body but they are required for maintenance of optimal health. There are two classes of polyunsaturated fatty acids (PUFAs)--omega-6 and omega-3.

The parent omega-6 fatty acid, linoleic acid (LA) is desaturated in the body to form arachidonic acid while parent omega-3 fatty acid alpha-linolenic acid (ALA) is desaturated by microsomal enzyme system through a series of metabolic steps to form eicosapentaenoic acid (EPA) and decosahexaenoic acid (DHA).

But there is a limited metabolic capability during early life to metabolize PUFAs to more active long-chain fatty acids. There is a critical role of EFAs and their metabolic products for maintenance of structural and functional integrity of central nervous system and retina. Most of the brain growth is completed by 5-6 years of age.

At birth brain weight is 70% of an adult, 15% brain growth occurs during infancy and remaining brain growth is completed during preschool years.

DHA is the predominant structural fatty acid in the central nervous system and retina and its availability is crucial for brain development.
It is recommended that the pregnant and nursing woman should take at least 2.6 g of omega-3 fatty acids and 100-300 mg of DHA daily to look after the needs of her fetus and suckling infant.

The follow-up studies have shown that infants of mothers supplemented with EFAs and DHA had higher mental processing scores, psychomotor development, eye-hand coordination and stereo acuity at 4 years of age.

Intake of EFAs and DHA during preschool years may also have a beneficial role in the prevention of attention deficit hyperactivity disorder (ADHD) and enhancing learning capability and academic performance.

Salam MT, Li YF, Langholz B, and Gilliland FD. Maternal fish consumption during pregnancy and risk of early childhood asthma. J Asthma, 2005; 42(6): 513-518.

Maternal fish consumption during pregnancy may affect children's asthma risk by modulating early-life immune development.

Type of fish intake may be important because of differences in fatty acid content.

To test this hypothesis, we conducted a nested case-control study, selecting subjects from the Children's Health Study, a population-based study of school-aged children in southern California.

Cases had physician-diagnosed asthma and controls were asthma-free by age 5 years. Mothers or guardians provided information on fish consumption during pregnancy in telephone interviews.
We computed odds ratio (OR) and 95% confidence interval (CI) by using conditional logistic regression models that accounted for the sampling.

In children born to mothers with a history of asthma, the OR of asthma was 0.20 (95% CI = 0.06-0.65) when mothers ate oily fish at least monthly during pregnancy compared with no consumption (p(trend) = 0.006).

Maternal oily fish consumption during pregnancy did not benefit children of non-asthmatic mothers.

In contrast, fish stick (a source of trans-fats) consumption during pregnancy increased asthma risk in children (OR = 2.04; 95% CI = 1.18-3.51).

Our results suggest that maternal oily fish intake during pregnancy may protect offspring from asthma; however, eating fish sticks during pregnancy may increase asthma risk in children.

Hibbeln JR. Seafood consumption, the DHA content of mothers' milk and prevalence rates of postpartum depression: a cross-national, ecological analysis. J Affect Disord,2002;69(1-3):15-29

BACKGROUND: Mothers selectively transfer docosahexaenoic acid (DHA) to their fetuses to support optimal neurological development during pregnancy.
Without sufficient dietary intake, mothers become depleted of DHA and may increase their risk of suffering major depressive symptoms in the postpartum period. We postulated that the DHA content of mothers' milk and seafood consumption would both predict prevalence rates of postpartum depression across countries.

METHODS: Published prevalence data for postpartum depression were included that used the Edinburgh Postpartum Depression Scale (n=14532 subjects in 41 studies). These data were compared to the DHA, eicosapentaenoic acid (EPA) and arachidonic acid (AA) content in mothers' milk and to seafood consumption rates in published reports from 23 countries.

RESULTS: Higher concentrations of DHA in mothers' milk (r=-0.84, p<0.0001, n=16 countries) and greater seafood consumption (r=-0.81, p<0.0001, n=22 countries) both predicted lower prevalence rates of postpartum depression in simple and logarithmic models, respectively.
The AA and EPA content of mothers' milk were unrelated to postpartum depression prevalence.

LIMITATIONS: These findings do not prove that higher omega-3 status cause lower prevalence rates of postpartum depression. Data on potentially confounding factors were not uniformly available for all countries.

CONCLUSIONS: Both lower DHA content in mothers' milk and lower seafood consumption were associated with higher rates of postpartum depression.

These results do not appear to be an artifact of cross-national differences in well-established risk factors for postpartum depression. Interventional studies are needed to determine if omega-3 fatty acids can reduce major postpartum depressive symptoms.

Stark K, Beblo S, et al. Comparison of bloodstream fatty acid composition from African-American women at gestation, delivery, and postpartum. J Lipid Research, 2005;(46):516-525

Our aim was to examine the docosahexaenoic acid (DHA; 22:6n-3) status of pregnant African-American women reporting to the antenatal clinic at Wayne State University in a longitudinal study design.

Fatty acid compositions of plasma and erythrocyte total lipid extracts were determined and food frequency surveys were administered at 24 weeks of gestation, delivery, and 3 months postpartum for participants (n = 157). DHA (mean ± SD) in the estimated total circulating plasma was similar at gestation (384 ± 162 mg) and delivery (372 ± 155 mg) but was significantly lower at 3 months postpartum (178 ± 81 mg).

The relative weight percentage of DHA and docosapentaenoic acid n-6 (DPAn-6; 22:5n-6) decreased postpartum, whereas their respective metabolic precursors, eicosapentaenoic acid (EPA; 20:5n-3) and arachidonic acid (AA; 20:4n-6), increased. Similar results were found in erythrocytes.

Dietary intake of DHA throughout the study was estimated at 68 ± 75 mg/day. The relative amounts of circulating DHA and DPAn-6 were increased during pregnancy compared with 3 months postpartum, possibly via increased synthesis from EPA and AA.

The low dietary intake and blood levels of DHA in this population compared with others may not support optimal fetal DHA accretion and subsequent neural development.

Foran JA, Good DH, et al. Quantitative Analysis of the Benefits and Risks of Consuming Farmed and Wild Salmon. J. Nutr., 2005;135:2639-2643.

Contaminants in farmed Atlantic and wild Pacific salmon raise important questions about the competing health benefits and risks of fish consumption.

A benefit-risk analysis was conducted to compare quantitatively the cancer and noncancer risks of exposure to organic contaminants in salmon with the (n-3) fatty acid?associated health benefits of salmon consumption.

Recommended levels of (n-3) fatty acid intake, as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), may be achieved by consuming farmed or wild salmon while maintaining an acceptable level of noncarcinogenic risk.
However, the recommended level of EPA+DHA intake cannot be achieved solely from farmed or wild salmon while maintaining an acceptable level of carcinogenic risk.

Although the benefit-risk ratio for carcinogens and noncarcinogens is significantly greater for wild Pacific salmon than for farmed Atlantic salmon as a group, the ratio for some subgroups of farmed salmon is on par with the ratio for wild salmon.

This analysis suggests that risk of exposure to contaminants in farmed and wild salmon is partially offset by the fatty acid?associated health benefits.

However, young children, women of child-bearing age, pregnant women, and nursing mothers not at significant risk for sudden cardiac death associated with CHD but concerned with health impairments such as reduction in IQ and other cognitive and behavioral effects, can minimize contaminant exposure by choosing the least contaminated wild salmon or by selecting other sources of (n-3) fatty acids.

Clandinin MT, Van Aerde JE, et al. Growth and development of preterm infants fed infant formulas containing docosahexaenoic acid and arachidonic acid. J Peds, 2005;146(4):461-468

Objectives To evaluate safety and benefits of feeding preterm infants formulas containing docosahexaenoic acid (DHA) and arachidonic acid (ARA) until 92 weeks postmenstrual age (PMA), with follow-up to 118 weeks PMA.

Study design This double-blinded study of 361 preterm infants randomized across three formula groups: (1) control, no supplementation; (2) algal-DHA (DHA from algal oil, ARA from fungal oil); and (3) fish-DHA (DHA from fish oil, ARA from fungal oil). Term infants breast-fed 4 months (n=105) were a reference group. Outcomes included growth, tolerance, adverse events, and Bayley development scores.

Results Weight of the algal-DHA group was significantly greater than the control group from 66 to 118 weeks PMA and the fish-DHA group at 118 weeks PMA but did not differ from term infants at 118 weeks PMA. The algal-DHA group was significantly longer than the control group at 48, 79, and 92 weeks PMA and the fish-DHA group at 57, 79, and 92 weeks PMA but did not differ from term infants from 79 to 118 weeks PMA. Supplemented groups had higher Bayley mental and psychomotor development scores at 118 weeks PMA than did the control group. Supplementation did not increase morbidity or adverse events.

Conclusions Feeding formulas with DHA and ARA from algal and fungal oils resulted in enhanced growth. Both supplemented formulas provided better developmental outcomes than unsupplemented formulas.

Agostoni C, Galli C, Riva E, et al. Reduced docosahexaenoic acid synthesis may contribute to growth restriction in infants born to mothers who smoke.
J Pediatr.,2005;147(6):854-856.

In newborn infants, progressive decrease in anthropometric values and impairment of the docosahexaenoic acid (DHA) status was associated with maternal smoking during pregnancy, with a parallel increase of the metabolic precursor of DHA, alpha-linolenic acid.

Maternal smoking may impair DHA synthesis which may contribute to reduced fetal growth.

PMID: 16356447

Genuis SJ, Schwalfenberg GK. Time for an oil check: the role of essential omega-3 fatty acids in maternal and pediatric health. J Perinatol, 2006;26(6):359-365.

Deficiency of omega-3 fatty acids (omega3FAs) is an often unrecognized determinant of clinical disease; the adequate availability of these essential nutrients may prevent affliction or facilitate health restoration in some pregnant women and developing offspring.

The human organism requires specific nutrients in order to carry out the molecular processes within cells and tissues and it is well established that omega3FAs are essential lipids necessary for various physiological functions.

Accordingly, to achieve optimal health for patients, care givers should be familiar with clinical aspects of nutritional science, including the assessment of nutritional status and judicious use of nutrient supplementation.

In view of the mounting evidence implicating omega3FA deficiency as a determinant of various maternal and pediatric afflictions, physicians should consider recommending purified fish oil supplementation during pregnancy and lactation.

Furthermore, omega3FA supplementation may be indicated in selected pediatric situations to promote optimal health among children.

PMID: 16688204

Javaid M, Crozier S, Harvey N, et al. Maternal vitamin D status during pregnancy and childhood bone mass at age 9 years: a longitudinal study. Lancet 2006; 367(9504): 36-43.

BACKGROUND: Vitamin D insufficiency is common in women of childbearing age and increasing evidence suggests that the risk of osteoporotic fracture in adulthood could be determined partly by environmental factors during intrauterine and early postnatal life. We investigated the effect of maternal vitamin D status during pregnancy on childhood skeletal growth.

METHODS: In a longitudinal study, we studied 198 children born in 1991-92 in a hospital in Southampton, UK; the body build, nutrition, and vitamin D status of their mothers had been characterised during pregnancy.
The children were followed up at age 9 years to relate these maternal characteristics to their body size and bone mass.

FINDINGS: 49 (31%) mothers had insufficient and 28 (18%) had deficient circulating concentrations of 25(OH)-vitamin D during late pregnancy.
Reduced concentration of 25(OH)-vitamin D in mothers during late pregnancy was associated with reduced whole-body (r=0.21, p=0.0088) and lumbar-spine (r=0.17, p=0.03) bone-mineral content in children at age 9 years.

Both the estimated exposure to ultraviolet B radiation during late pregnancy and the maternal use of vitamin D supplements predicted maternal 25(OH)-vitamin D concentration (p<0.0001 and p=0.0110, respectively) and childhood bone mass (p=0.0267). Reduced concentration of umbilical-venous calcium also predicted reduced childhood bone mass (p=0.0286).

INTERPRETATION: Maternal vitamin D insufficiency is common during pregnancy and is associated with reduced bone-mineral accrual in the offspring during childhood; this association is mediated partly through the concentration of umbilical venous calcium.

Vitamin D supplementation of pregnant women, especially during winter months, could lead to longlasting reductions in the risk of osteoporotic fracture in their offspring.

Hoffman D, Uauy R. Essentiality of dietary omega 3 fatty acids for premature infants: plasma and red blood cell fatty acid composition. Lipids 1992; 27(11): 886-895

Pre-term infants, that are not breast-fed, are deprived of vital intrauterine fat accretion during late pregnancy and must rely on formula to obtain fatty acids essential for normal development, particularly of the visual system.

Preterm infants (30 wk postconception) receiving human milk were compared to infants given one of the following formulae: Formula A was a commercial preterm formula with predominantly 18:2 omega 6 (24.2%) and low (0.5%) 18:3 omega 3; Formula B was based on soy oil and contained similar 18:2 omega 6 levels (20%) and high 18:3 omega 3 (2.7%); Formula C was also a soy oil-based formula (20% 18:2, 1.4% 18:3) but was supplemented with marine oil to provide omega 3 long-chain polyunsaturated fatty acids (LCP) at a level (docosahexaenoic acid, DHA, 0.35%) equivalent to human milk.

At entry (10 days of age), the fatty acid composition of plasma and red blood cell (RBC) membrane lipids of the formula groups were identical. By 36 wk postconception, the DHA content in lipids of group A was significantly reduced compared to that in the human milk and marine oil formula groups.

Omega-3 LCP results were further amplified by 57 wk with compensatory increases in 22:5 omega 6 in both plasma and RBC lipids. Provision of 2.7% alpha-linolenic acid in formula group B was sufficient to maintain 22:6 omega 3 levels equivalent to those in human milk-fed infants at 36 wk but not at 57 wk.

Effects on the production of thiobarbituric acid reactive substances and fragility of RBC attributable to the marine oil supplementation were negligible. The results support the essentiality of omega 3 fatty acids for preterm infants to obtain fatty acid profiles comparable to infants receiving human milk. Formula for preterm infants should be supplemented with omega 3 fatty acids including LCP.

SR De Vriese, AB Christophe, and M Maes. Lowered serum n-3 polyunsaturated fatty acid (PUFA) levels predict the occurrence of postpartum depression: further evidence that lowered n-PUFAs are related to major depression. Life Sci, 2003;73(25):3181-318

Several studies have shown that major depression is accompanied by alterations in serum fatty acid composition, e.g. reduced n-3 fatty acids and an increased 20:4n-6/20:5n-3 ratio in serum. Moreover, pregnancy leads to depletion of maternal serum 22:6n-3 and after delivery maternal serum 22:6n-3 steadily declines further.

Therefore, the aim of the present study was to investigate whether the postpartum fatty acid profile of maternal serum phospholipids (PL) and cholesteryl esters (CE) differs in women who develop postpartum depression compared to controls.

We compared the fatty acid composition shortly after delivery of 10 women who developed postpartum depression and 38 women who did not.

After delivery, 22:6n-3 and the sum of the n-3 fatty acids in PL and CE was significantly lower in the group of mothers who developed a postpartum depression. The ratio of Sigman-6/Sigman-3 fatty acids in PL was, postpartum, significantly higher in the depressed group as compared to the controls.

The abnormalities in fatty acid status previously observed in major depression are now also confirmed in postpartum depression. These results indicate that pregnant women who are at risk to develop postpartum depression may benefit from a prophylactic treatment with n-3 PUFAs, such as a combination of 20:5n-3 and 22:6n-3.

RT Holman, SB Johnson and PL Ogburn. Deficiency of Essential Fatty Acids and Membrane Fluidity During Pregnancy and Lactation. Proceedings of the National Academy of Sciences, 1991;(88): 4835-4839

In a group of 19 normal pregnant women, plasma lipids were extracted, phospholipids were isolated, and the fatty acid (FA) compositions were measured by capillary gas chromatography. Blood samples were taken at 36 wk, at labor, and at 6 wk postpartum.

The FA profiles showed deficiencies of 6 and 3 FA (indicating the length of the terminal saturated chain), the latter more severe, at all three times.

Mean melting point (MMP) was calculated for each sample as an index of "fluidity" based upon all FA present. MMP varied linearly with total polyunsaturated FA and with double bond index, current measures of "fluidity" and essential FA status.

MMP was elevated 9-11C in plasma phospholipids of women during pregnancy and labor and postpartum. Lactating mothers showed less recovery from the deficiencies than did the nonlactating mothers, but neither approached normal at 6 wk.

The changes seen in phospholipid profiles suggest a significant transfer of 3 and 6 polyunsaturated FA from the mother to the fetus. These FA are essential for normal fetal growth and development; their relative deficiency in maternal circulation suggests that dietary supplementation may be indicated.

Mothers who supplement their diet with fatty acids rich in docosahexaenoic acid (DHA) during pregnancy and lactation may be doing their children a favour in later years, say researchers in this month?s Pediatrics Journal.

Researchers in Norway examining the effects of DHA on mental development found that those children whose mothers had a higher intake of DHA during pregnancy scored higher on intelligence and achievement tests at four years of age than those whose mothers took fatty acids not containing DHA.

The researchers at the University of Oslo enrolled women during the 18th week of pregnancy in a randomized, double-blind trial and supplemented their diets with one of two different polyunsaturated fatty acids (PUFAs).

Participants received either cod liver oil (containing very-long-chain omega-3 PUFA rich in DHA and other omega-3 fatty acids) or corn oil (a long-chain omega-6 PUFA with no DHA content). They took the supplements from the point of enrollment until three months after childbirth.
Researchers then completed assessments of intelligence using the Kaufman Assessment Battery for Children (K-ABC) for 84 child subjects once they reached four years of age.

The team found that children born to mothers who had taken the cod liver oil during pregnancy and lactation scored significantly higher (approximately 4.1 points) on the Mental Processing Composite of the K-ABC test compared to children whose mothers had received corn oil.
The researchers classified these increases as significant.

Source: http://www.nutraingredients.com/news/news.asp?id=6185

Pregnant women who eat more of a key fatty acid found in fish give their babies better chances of mature brain development, finds a new study in the September issue of the American Journal of Clinical Nutrition.

The study also found that mothers with more docosahexaenoic acid (DHA) in their blood had babies with heartier sleep patterns in the first 48 hours after delivery compared to those whose mothers consumed less of the compound.

In a report on the study, Healthscoutnews noted that infant sleep patterns are thought to reflect the maturity of a child?s nervous system, and have been associated with more rapid development in their first year of life.

The omega-3 fatty acid, DHA, along with another substance, arachidonic acid (AA), are key building blocks in breast milk that contribute to healthy brain and eye development. Infant formula makers, such as Ross Products and Mead Johnson Nutritionals, are beginning to recognize the value of the compounds and have said they will add them to some of their brands.
The two substances are also passed from mother to foetus across the placenta. Some 70 percent of brain cell development takes place during gestation.

In the study, Carol Lammi-Keefe and her colleagues at the University of Connecticut compared DHA levels and newborn sleep patterns in 17 women and their babies. Ten of the women had high blood concentrations of DHA - considered to be more than 3 per cent of their total circulating fatty acids - while seven had less than that amount.
Healthscoutnews noted that Lammi-Keefe's group did not ask the women about their diets. None of the subjects in the study had DHA levels that reflected eating fish more than three times a week, as recommended by many experts. Other foods, like eggs and red meat, contain modest amounts of the nutrient, but cold-water fish such as tuna and mackerel are considered the best source.

Women with low DHA were more likely to be minorities and to have received fewer years of education. They were also five years younger, on average, than those in the high DHA category - 24 versus 29 years, according to the report.

All the babies were delivered vaginally and none of the women had been given drugs known to make newborns lethargic, the researchers said.

Using a motion-sensing pad to measure breathing and movement during sleep cycles, the researchers found babies of women in the low-DHA group had less advanced sleeping patterns than the other infants. They had a greater ratio of "active" to "quiet" sleep, spent more time transitioning between sleeping and waking, and spent less time fully awake than those of women with higher blood levels of the fatty acid.

"As an infant matures, normally you would see the infant spending more time in a wakeful state," Lammi-Keefe said. "Infants born to mothers with more DHA have sleep characteristics of a more mature central nervous system compared with the infants of mothers with lower DHA levels."

June Machover Reinisch, director emerita of the Kinsey Institute and a child development expert, said the findings seemed to echo the importance of breast feeding for optimal infant growth, although she noted that many other factors, from method of delivery and the use of anesthesia during labour to the infant's gender, can influence a newborn's wakefulness.

"We have to be flexible in our definition of development," Machover Reinisch said. "With the child who sleeps not as well at two days, it may be related to the DHA, but it doesn't necessarily mean that there's going to be a problem with that child."

Researchers have correlated newborn sleep states with performance on mental and motor developmental tests at 9 months of age. However, both Lammi-Keefe and Reinisch said there is no way to predict whether a child with less mature sleeping habits in the first week of life will be anything other than healthy.

The researchers are currently organizing a one-year study to investigate dietary intake of DHA in pregnant women.

Source: http://www.nutraingredients.com/news/news.asp?id=5217

Babies benefit from omega-3 fatty acids from womb to high chair

Anaheim, Calif. Mothers who eat foods rich in omega-3 fatty acids during pregnancy and while nursing, and who continue to feed their babies such a diet after weaning, may reduce their daughters' risk of developing breast cancer later in life dramatically, according to research presented here today at the 96th Annual Meeting of the American Association for Cancer Research.

Either maternal or post-weaning dietary consumption of this type of fat that is, taking in omega-3 fatty acids through food or supplements at any point in life from conception to at least puberty also could reduce the incidence rate for breast cancer in female offspring significantly.

Conversely, mothers' consumption of omega-6 fats commonly found in Western diets could increase their daughters' risk of breast cancer.

"Diet matters, Mom," said W. Elaine Hardman, Ph.D., an assistant professor in the Division of Functional Foods at the Pennington Biomedical Research Center, Louisiana State University, Baton Rouge. "Inadvertently, we may be setting up our daughters to develop breast cancer 50 years from now."

Both omega-6 and omega-3 fatty acids are essential for human health; however, particularly in the Western hemisphere, omega-6 fatty acids far exceed omega-3 fatty acids in the typical diet. Meat, eggs, poultry, cereals, breads, baked goods, most vegetable oils, and margarine are among dietary sources of omega-6 fatty acids.

Omega-3 fatty acids occur most commonly in fish especially cold-water fish such as tuna, salmon and mackerel as well as in canola and flaxseed oils, soybeans and nuts.

Hardman based her hypothesis on existing research showing that maternal diets containing high amounts of omega-6 fatty acids increase maternal estrogen levels; increased maternal estrogen, in turn, has been linked to an increased incidence of breast cancer among female offspring.

Meanwhile, many foods rich in omega-3 fatty acids are known to block the effects of estrogen and boost immunity.

Working with mice bred with a genetic predisposition to develop breast cancer, Hardman compared the incidence rates for the disease in offspring depending upon theirs and their mothers' relative consumption of diets either high in omega-6 fatty acids, or high in omega-3 fatty acids.

The genetic make-up of the female mice was such that all would develop hyperplasia; that is, to grow too many normal cells, in the mammary ducts, by three months of age. By six months, that hyperplasia would progress to mammary adenocarcinoma.

The mice were bred and the mothers were fed diets high in either omega-6 fatty acids or high in omega-3 fatty acids, both during the gestation period and while breast-feeding the female young. After the daughters were weaned, one group was placed on a high-omega-6 fatty acid diet, while the other was fed predominantly omega-3 fatty acids.

In Hardman's experiment, all the young exposed only to omega-6 fatty acids, in utero, in nursing and after weaning, showed mammary gland tumors by six months of age. Conversely, fewer than 60 percent of the female offspring who ate richly of high omega-3 fatty acids either maternally or post-weaning formed mammary tumors by the age of eight months. Those exposed to omega-3 fatty acids both maternally and after weaning had a tumor incidence rate of just 13 percent.

The beauty of the mouse model, Hardman explains, is the ability it gives researchers to collapse an entire life-span into a matter of months, instead of years. By using mice programmed genetically to develop tumors in the mammary glands eliminates the element of chance.

Harman has observed suppression of tumor growth with as little as two percent omega-3 fatty acids in the diet.

"A couple of servings a week may be enough," she said. "A quarter of a cup of walnuts constitutes one serving."

For pregnant women who are concerned about ingesting mercury in fish, Hardman recommends fish oil supplements, readily available in grocery, drug and health food stores. The fish oil in supplements is well purified.

Source: http://www.eurekalert.org/pub_releases/2005-04/aafc-mpa041205.php

Eating oily fish and seeds in pregnancy can boost children's future brain power and social skills, research suggests.

A study of 9,000 mothers and children in Avon suggested those who consumed less of the essential fatty acid Omega-3 had children with lower IQs.

These children also had poorer motor skills and hand-to-eye co-ordination, research in the Economist said.

The Food Standards Agency says pregnant women should consume only one or two portions of oily fish a week.

A team from the National Institutes of Health in the US analysed data from a long-term study done in Avon, UK.



Looking at the effects of Omega-3 intake on 9,000 mothers and their children, the team found mothers with the lowest intake of the essential fatty acid had children with a verbal IQ six points lower than the average.

While those with the highest consumption of mackerel and sardines and other sources of Omega-3 had children, at age three-and-a-half, with the best measures of fine-motor performance, researchers said.

Low intake of the crucial fatty acid also appeared to lead to more problems of social interactions - such as an inability to make friends.

Research leader Dr Joseph Hibbeln said "frightening data" showed 14% of 17-year-olds whose mother had eaten small quantities of Omega -3 during pregnancy demonstrated this sort of behaviour.

This compared with 8% of those born to the group with the highest intake, he said.

Dr Hibbeln said: "The findings of poor social development and poor motor control in children indicate that these children may be on a developmental trajectory towards lifelong disruptive and poorly-socialised behaviour as they grow up."

It's absolutely essential that pregnant women take in enough Omega-3 and that children in early infancy take in enough Omega-3



Professor Jean Golding of Bristol University set up the original research - the Avon Longitudinal Study of Parents and Children -15 years ago to look at the predisposition to disease.

She told the BBC: "The baby's brain needs Omega-3 fatty acids. It doesn't create its own fatty acids so it needs to be something that the mother will eat."

The new research also builds on earlier work in the US which suggests pregnant mothers will develop children with better language and communication skills if they regularly consume oily fish.

Nutritional expert Patrick Holford, director of the Brain Bio Centre, said Omega-3 was key to children's intelligence because the brain is formed of 60% fat - 30% of which is essential fats.

Successive studies have shown clear links between intelligence and consumption of this essential fatty acid, he added.

"It's absolutely essential that pregnant women take in enough Omega-3 and that children in early infancy take in enough Omega-3."

The richest sources of Omega-3 are larger fish which eat other fish, but research shows that the larger the fish the more pollutants, such as mercury, they contain.

For this reason Mr Holford recommends women consume two portions of wild or organic salmon, trout or sardines weekly.

Seeds such as flax, pumpkin and hemp are good sources of Omega-3 for vegetarians, but large quantities need to be consumed to gain the same effect.

This might translate to two tablespoons of seeds daily, Mr Holford said, but women can also use a high quality Omega-3 supplements.
Source: http://news.bbc.co.uk/2/hi/health/4631006.stm

Women in Coastal Areas Are Found to Have Higher Mercury Levels

By Juliet Eilperin
Washington Post Staff Writer

Women in coastal communities have twice as much mercury in their blood as those living inland, according to an analysis by an Environmental Protection Agency scientist.

The preliminary findings, based on a survey of 3,600 women conducted by the Centers for Disease Control and Prevention between 1999 and 2002, provide fresh evidence of the link between fish consumption and concentrations of methylmercury, a neurotoxin that causes developmental problems in young children.

The study focused on the 10 percent of women with the highest mercury levels, and in that group, it found that inland residents had an average level of 2.4 parts per billion, compared with 5.9 parts per billion for coastal residents. EPA guidelines hold that mercury levels higher than 3.5 parts per billion pose a possible health threat.

Mercury, spewed into the air in emissions from power plants and other sources, ends up in water and accumulates in predator fish such as tuna and swordfish. In pregnant women with high levels, methylmercury crosses the placenta and can affect the developing brain of the fetus.

"What's evident in these data is there's a real difference between the coastal and non-coastal" women, said Kathryn Mahaffey, who conducted the analysis as director of the EPA's division of exposure assessment, coordination and policy. "The message is people need to eat a variety of foods and, when choosing fish species, they need to choose more than one type of fish."

The EPA recommends that women of childbearing age limit their albacore tuna consumption to six ounces, or an average meal, a week. The agency suggests that women eat as much as 12 ounces a week of fish or shellfish that are lower in mercury, such as salmon, shrimp and trout.

Mahaffey said agency scientists did not obtain a detailed diet breakdown from the women, but they assumed that those living in coastal areas ate more fish. A study published this year found that French women living on the coast consume three times as much fish as those living inland.

American women living on the Atlantic Coast had much higher mercury levels than those living on the Pacific or Gulf coasts. Atlantic Coast residents had average levels of 7.7 parts per billion, while women on the Pacific had levels of 4.7 and women on the Gulf Coast had 3.2 parts per billion.

Mahaffey said she could not account for the discrepancy, adding, "Fish are just not all the same."

The study, obtained by The Washington Post from the nonprofit Natural Resources News Service, also indicated that wealthier women were more likely than poor women to have elevated mercury levels. Women earning less than $20,000 annually had an average level of 2.8 parts per billion, while women earning more than $20,000 had 3.9 parts per billion.

Environmentalists said the survey -- along with another this week in the journal Environmental Health Perspectives that showed Asian, Pacific Islander and Native American women have higher mercury levels than women from other backgrounds -- should remind Americans of the health dangers contaminated fish can pose.

"It reaffirms there's a strong connection to ocean fish, but that's not to say non-coastal residents are safe," said Jackie Savitz, who directs the seafood contamination campaign at Oceana, an advocacy group. "Alarms should really be sounded for everyone."

Oceana has lobbied grocery store chains -- including Safeway, Wal-Mart and Whole Foods -- to post signs identifying which fish are high in mercury.

Source: http://www.washingtonpost.com/wp-dyn/content/article/2005/09/22/AR2005092201899.html

Naliwaiko K, Araujo R, et al. Effects of fish oil on the central nervous system: a new potential antidepressant? Nutr Neurosci, 2004;7(2):91-99

In the last 100 years major depression has increased worldwide. In this study we provided coconut fat (CF, rich in saturated fatty acids) or fish oil (FO, rich in n-3 polyunsaturated fatty acids) to female rats throughout pregnancy and lactation and then to their offspring post-weaning and examined lipid brain profile and the possible effect of FO as antidepressant agent in the offspring in adulthood (F1).

Rats were submitted to forced swimming test, elevated plus maze, Morris water maze and open field. Peroxidation rate in the cerebral cortex and hippocampus were measured.

Docosahexaenoic acid (DHA) concentration in dam's milk, eicosapentaenoic acid (EPA) and DHA concentration in hippocampus and cerebral cortex from F1 rats FO supplemented increased significantly when compared to control (C) and CF rats. Arachidonic acid/EPA ratio in the cerebral cortex and hippocampus decreased in rats submitted to forced swimming test. Peroxidation rate were not different between the groups. Immobility time in the forced swimming test in FO group was reduced (p < 0.01) when compared to C and CF rats.

We conclude that lifelong intake of FO was able to induce an antidepressant effect with EPA and DHA concentration increased in the cerebral cortex and hippocampus.

Holman R, Johnson S, Ogburn P. Deficiency of Essential Fatty Acids and Membrane Fluidity During Pregnancy and Lactation. PNAS 1991; 88: 4835-4839.

In a group of 19 normal pregnant women, plasma lipids were extracted, phospholipids were isolated, and the fatty acid (FA) compositions were measured by capillary gas chromatography. Blood samples were taken at 36 wk, at labor, and at 6 wk postpartum. The FA profiles showed deficiencies of 6 and 3 FA ( indicating the length of the terminal saturated chain), the latter more severe, at all three times. Mean melting point (MMP) was calculated for each sample as an index of "fluidity" based upon all FA present. MMP varied linearly with total polyunsaturated FA and with double bond index, current measures of "fluidity" and essential FA status. MMP was elevated 9-11C in plasma phospholipids of women during pregnancy and labor and postpartum. Lactating mothers showed less recovery from the deficiencies than did the nonlactating mothers, but neither approached normal at 6 wk. The changes seen in phospholipid profiles suggest a significant transfer of 3 and 6 polyunsaturated FA from the mother to the fetus. These FA are essential for normal fetal growth and development; their relative deficiency in maternal circulation suggests that dietary supplementation may be indicated.

Peds - Helland IB, Smith L, Saarem K, et al. Maternal supplementation with very-long-chain n-3 fatty acids during pregnancy and lactation augments children?s IQ at 4 years of age. Pediatrics 2003 Jan;111(1):39-44.

OBJECTIVES: Docosahexaenoic acid (DHA; 22:6 n-3) and arachidonic acid (AA; 20:4 n-6) are important for development of the central nervous system in mammals. There is a growth spurt in the human brain during the last trimester of pregnancy and the first postnatal months, with a large increase in the cerebral content of AA and DHA. The fetus and the newborn infant depend on maternal supply of DHA and AA.

Our hypothesis was that maternal intake of DHA during pregnancy and lactation is marginal and that high intake of this fatty acid would benefit the child. We examined the effect of supplementing pregnant and lactating women with very-long-chain n-3 polyunsaturated fatty acids (PUFAs; cod liver oil) on mental development of the children, compared with maternal supplementation with long-chain n-6 PUFAs (corn oil).

METHODS: The study was randomized and double-blinded. Pregnant women were recruited in week 18 of pregnancy to take 10 mL of cod liver oil or corn oil until 3 months after delivery. The cod liver oil contained 1183 mg/10 mL DHA, 803 mg/10 mL eicosapentaenoic acid (20:5 n-3), and a total of 2494 mg/10 mL summation operator n-3 PUFAs. The corn oil contained 4747 mg/10 mL linoleic acid (18:2 n-6)