Maternal Long-chain Polyunsaturated Fatty Acids Research Articles

Association of Fatty Acid Desaturase 1 rs174547 Polymorphism with the Composition of Long-Chain Polyunsaturated Fatty Acids in Serum Glycerophospholipids during Pregnancy.

The increase in fetal requirements of long-chain polyunsaturated fatty acids (LCPUFAs) during pregnancy alters maternal fatty acid metabolism, and therefore, fatty acid desaturase (FADS) gene polymorphisms may change blood fatty acid composition or concentration differently during pregnancy. We investigated the relationship between a FADS1 single-nucleotide polymorphism (SNP) and maternal serum LCPUFA levels in Japanese pregnant women during the first and third trimesters and at delivery. Two hundred and fifty-three pregnant women were included, and fatty acid compositions of glycerophospholipids in serum (weight %) and the FADS1 SNP rs174547 (T/C) were analyzed. LCPUFAs, including arachidonic acid (ARA) and docosahexaenoic acid (DHA), significantly decreased from the first to the third trimester of pregnancy. Furthermore, DHA significantly decreased from the third trimester of pregnancy to delivery. At all gestational stages, linoleic acid (LA) and α-linolenic acid were significantly higher with the number of minor FADS1 SNP alleles, whereas γ-linolenic acid and ARA and the ARA/LA ratio were significantly lower. DHA was significantly lower with the number of minor FADS1 SNP alleles only in the third trimester and at delivery, suggesting that genotype effects become more obvious as pregnancy progresses.

Maternal omega-3 LC-PUFA supplementation programs an improved bone mass in the offspring with a more pronounced effect in females than males at adulthood

Early balanced nutrition is vital in achieving optimal skeletal mass and its maintenance. Although a lower omega-6 (n-6): omega-3 (n-3) long-chain polyunsaturated fatty acid (LC-PUFA) ratio is strongly linked with bone health, its maternal effect in the programming of the offspring's skeleton remains to be elucidated. Plugged C57BL/6 mice were fed either n-3 LC-PUFA Enriched Diet (LED) or a control diet (C) throughout their gestation and lactation. Offspring born to both the groups were weaned onto C till 6, 12, and 24 weeks of their age. Offspring's skeleton metabolism and serum fatty acid composition was studied. In humans, seventy-five mother-female newborns pairs from term gestation were tested for their maternal LC-PUFA status relationships to venous cord blood bone biomarkers. Offspring of maternal LED supplemented mice exhibited a superior bone phenotype over C, more prominent in females than males. A lower serum n-6/n-3 LC-PUFA in the LED group offspring was strongly associated with blood biomarkers of bone metabolism. Sexual dimorphism evidenced had a strong correlation between offspring's LC-PUFA levels and bone turnover markers in serum. A higher potential for osteoblastic differentiation in both LED offspring genders and reduced osteoclastogenesis in females was cell-autonomous effect. The human cross-sectional study also showed a positive correlation between maternal n-3 PUFA and cord blood markers of bone formation in female newborns at birth. Maternal dietary n-6/ n-3 fat quality determines offspring's bone growth and development. Our data suggest that the skeleton of female offspring is likely to be more sensitive to this early exposure.

Maternal Plasma Glycerophospholipids LC-PUFA Levels Have a Sex-Specific Association with the Offspring's Cord Plasma Glycerophospholipids-Fatty Acid Desaturation Indices at Birth.

Fatty acid desaturases, the enzymes responsible for the production of unsaturated fatty acids (FA) in fetal tissues, are known to be influenced by maternal-placental supply of nutrients and hormones for their function. We hypothesize that there could be a gender-specific regulation of unsaturated FA metabolism at birth, dependent on the maternal fatty acid levels. In this study, 153 mother-newborn pairs of uncomplicated and 'full-term' pregnancies were selected and the FA composition of plasma glycerophospholipids (GP) was quantified by gas chromatography. The FA composition of mother blood plasma (MB) was compared with the respective cord blood plasma (CB) of male newborns or female newborns. Product to substrate ratios were estimated to calculate delta 5 desaturase (D5D), delta 6 desaturase (D6D) and delta 9 stearoyl-CoA-desaturase (D9D/SCD) indices. Pearson correlations and linear regression analyses were employed to determine the associations between MB and CB pairs. In the results, the male infant's MB-CB association was positively correlated with the SCD index of carbon-16 FA, while no correlation was seen for the SCD index of carbon-18 FA. Unlike for males, the CB-D5D index of female neonates presented a strong positive association with the maternal n-6 long chain-polyunsaturated FA (LC-PUFA), arachidonic acid. In addition, the lipogenic desaturation index of SCD18 in the CB of female new-borns was negatively correlated with their MB n-3 DHA. In conclusion, sex-related differences in new-borns' CB desaturation indices are associated with maternal LC-PUFA status at the time of the birth. This examined relationship appears to predict the origin of sex-specific unsaturated FA metabolism seen in later life.

Maternal and Neonatal Polyunsaturated Fatty Acid Intake and Risk of Neurodevelopmental Impairment in Premature Infants.

The N3 and N6 long chain polyunsaturated fatty acids (LCPUFA) docosahexaenoic acid (DHA) and arachidonic acid (AA) are essential for proper neurodevelopment in early life. These fatty acids are passed from mother to infant via the placenta, accreting into fetal tissues such as brain and adipose tissue. Placental transfer of LCPUFA is highest in the final trimester, but this transfer is abruptly severed with premature birth. As such, efforts have been made to supplement the post-natal feed of premature infants with LCPUFA to improve neurodevelopmental outcomes. This narrative review analyzes the current body of evidence pertinent to neurodevelopmental outcomes after LCPUFA supplementation in prematurely born infants, which was identified via the reference lists of systematic and narrative reviews and PubMed search engine results. This review finds that, while the evidence is weakened by heterogeneity, it may be seen that feed comprising 0.3% DHA and 0.6% AA is associated with more positive neurodevelopmental outcomes than LCPUFA-deplete feed. While no new RCTs have been performed since the most recent Cochrane meta-analysis in 2016, this narrative review provides a wider commentary; the wider effects of LCPUFA supplementation in prematurely born infants, the physiology of LCPUFA accretion into preterm tissues, and the physiological effects of LCPUFA that affect neurodevelopment. We also discuss the roles of maternal LCPUFA status as a modifiable factor affecting the risk of preterm birth and infant neurodevelopmental outcomes. To better understand the role of LCPUFAs in infant neurodevelopment, future study designs must consider absolute and relative availabilities of all LCPUFA species and incorporate the LCPUFA status of both mother and infant in pre- and postnatal periods.

Maternal long-chain polyunsaturated fatty acid status during early pregnancy: Association with child behavioral problems and the role of autonomic nervous system activity

The prenatal environment, including availability of critical nutrients, has a profound impact on offspring development. The present study examined the association between maternal long-chain polyunsaturated fatty acid (LC-PUFA) status during pregnancy and later child behavioral problems at the age of 5-6 years. In light of evidence of autonomic nervous system (ANS) dysregulation in some behavioral problems, study further tested if the above association is statistically mediated by cardiac ANS activity. Data was collected as part of the Amsterdam Born Children and their Development-study and complete data were available for 1717 mothers and their offspring. Maternal LC-PUFA status was assessed during early pregnancy (mean gestation=12.7, SD=2.5 weeks) and quantified as levels of docosahexenoic acid (DHA), arachidonic acid (AA), eicosapentaenoic acid (EPA), as well as the ratio of n-6:n-3 fatty acids. Child emotional problems and peer problems (internalizing problems), as well as conduct problems and inattention/hyperactivity (externalizing problems), were assessed using the Strengths and Difficulties Questionnaire as rated by the mother and teacher at 5-6 years. Child cardiac respiratory sinus arrhythmia (RSA), pre-ejection period (PEP), and heart rate (HR) were utilized as measures of ANS activity at 5-6 years. The results confirmed an association between maternal LC-PUFA status and internalizing behavioral problems as rated by the mother, as shown for DHA (β=-0.11;p<0.01), EPA (β=-0.22;p<0.05), and n-6:n-3 LC-PUFA (β=0.17;p<0.01). Statistical mediation was only demonstrated for HR. No associations were observed between LC-PUFA status and externalizing behavioral problems. The present results are consistent with a role of maternal LC-PUFA status in internalizing behavioral problems as rated by the mother. These results were not observed when problem behavior was rated by the teacher. Analyses did not yield strong evidence supporting ANS activity as a possible mediator in this relationship.

Maternal Long-Chain Polyunsaturated Fatty Acid Status, Methylmercury Exposure, and Birth Outcomes in a High-Fish-Eating Mother–Child Cohort

Maternal status of long-chain PUFAs (LC-PUFAs) may be related to fetal growth. Maternal fish consumption exposes the mother to the neurotoxicant methylmercury (MeHg), which, in contrast, may restrict fetal growth. Our aim was to examine relations between maternal LC-PUFA status at 28 wk and birth outcomes (birth weight, length, and head circumference), controlling for MeHg exposure throughout pregnancy, in the Seychelles Child Development Study Nutrition Cohort 2. Our secondary aim was to examine the influence of maternal variation in genes regulating the desaturation of LC-PUFAs [fatty acid desaturase (FADS)] on birth outcomes. From nonfasting blood samples collected at 28 wk of gestation, we measured serum total LC-PUFA concentrations and FADS1 (rs174537, rs174561), FADS1-FADS2rs3834458, and FADS2rs174575 genotypes, with hair total mercury concentrations assessed at delivery. Data were available for n=1236 mother-child pairs. Associations of maternal LC-PUFAs, MeHg, and FADS genotype with birth outcomes were assessed by multiple linear regression models, adjusting for child sex, gestational age, maternal age, BMI, alcohol use, socioeconomic status, and parity. In our cohort of healthy mothers, neither maternal LC-PUFA status nor MeHg exposure were significant determinants of birth outcomes. However, when compared with major allele homozygotes, mothers who were heterozygous for the minor allele of FADS1 (rs174537 and rs174561, GT compared with TT, β = 0.205, P=0.03; TC compared with CC, β = 0.203, P=0.04) and FADS1-FADS2 (rs3834458, Tdel compared with DelDel, β = 0.197, P=0.04) had infants with a greater head circumference (all P<0.05). Homozygosity for the minor allele of FADS2 (rs174575) was associated with a greater birth weight (GG compared with CC, β = 0.109, P=0.04). In our mother-child cohort, neither maternal LC-PUFA status nor MeHg exposure was associated with birth outcomes. The observed associations of variation in maternal FADS genotype with birth outcomes should be confirmed in other populations.

Maternal dietary deficiency of n-3 fatty acids affects metabolic and epigenetic phenotypes of the developing fetus

Polyunsaturated fatty acids (PUFAs) play multiple physiological roles. They regulate the structure and function of cell membranes and cell growth and proliferation, and apoptosis. In addition, PUFAs are involved in cellular signaling, gene expression and serve as precursors to second messengers such as eicosanoids, docosanoids etc. and regulate several physiological processes including placentation, inflammation, immunity, angiogenesis, platelet function, synaptic plasticity, neurogenesis, bone formation, energy homeostasis, pain sensitivity, stress, and cognitive functions. Linoleic acid, 18:2n-6 (LA) and alpha-linolenic acid, 18:3n-3 (ALA) are the two essential fatty acids obtained from the diets and subsequently their long-chain polyunsaturated fatty acids (LCPUFAs) are accumulated in the body. The maternal plasma LCPUFAs especially accumulated in larger amounts in the brain during the third trimester of pregnancy via the placenta and postnatally from mother's breast milk. Various studies, including ours, suggest PUFA's important role in placentation, as well as in growth and development of the offspring. However, intakes of maternal n-3 PUFAs during pregnancy and lactation are much lower in India compared with the Western population. In India, n-3 fatty acid status is further reduced by higher intake of n-6 PUFA rich oils and trans fats. More data on the impacts of long term maternal n-3 PUFA deficiency on placental structure and function, gene expression, epigenetic changes and resultant cognitive function of fetus & infants are emerging. This review summarizes the impacts of n-3 PUFA deficiency in utero on fetal growth and development, adiposity, energy metabolism, musculoskeletal development, and epigenetic changes in feto-placental axis from the recently available pre-clinical and clinical data.

The REVAMP study: research exploring various aspects and mechanisms in preeclampsia: study protocol

BackgroundPreeclampsia is a major cause of maternal, fetal and neonatal morbidity and mortality, particularly in developing countries. Considering the burden of preeclampsia and its associated complications, it is important to understand the underlying risk factors and mechanisms involved in its etiology. There is considerable interest in the potential for dietary long chain polyunsaturated fatty acids (LCPUFA) as a therapeutic intervention to prevent preeclampsia, as they are involved in angiogenesis, oxidative stress, and inflammatory pathways.MethodsThe REVAMP study (Research Exploring Various Aspects and Mechanisms in Preeclampsia) follows a cohort of pregnant women from early pregnancy until delivery to examine longitudinally the associations of maternal LCPUFA with clinical outcome in preeclampsia. A multisite centre for advanced research was established and pregnant women coming to Bharati hospital and Gupte hospital, Pune, India for their first antenatal visit are recruited and followed up at 11–14 weeks, 18–22 weeks, 26–28 weeks, and at delivery. Their personal, obstetric, clinical, and family history are recorded. Anthropometric measures (height, weight), food frequency questionnaire (FFQ), physical activity, socioeconomic status, fetal ultrasonography, and color Doppler measures are recorded at different time points across gestation. Maternal blood at all time points, cord blood, and placenta at delivery are collected, processed and stored at − 80 °C. The children’s anthropometry is assessed serially up to the age of 2 years, when their neurodevelopmental scores will be assessed.DiscussionThis study will help in early identification of pregnant women who are at risk of developing preeclampsia. The prospective design of the study for the first time will establish the role of LCPUFA in understanding the underlying biochemical and molecular mechanisms involved in preeclampsia and their association with developmental programming in children.

Effect of gestational oily fish intake on the risk of allergy in children may be influenced by FADS1/2, ELOVL5 expression and DNA methylation

BackgroundEvidence suggests that prenatal exposure to n-3 long-chain polyunsaturated fatty acids (LCPUFA) reduces the incidence of allergic disease in children. LCPUFAs are produced from dietary precursors catalyzed by desaturases and elongases encoded by the FADS1/2 and ELOVL5 genes. DNA methylation regulates gene activity and fatty acid supplementation could alter DNA methylation (DNA-M) at these genes. We investigated whether DNA-M and expression of the FADS1/2 and ELOVL5 genes were associated with allergy in children and gestational fish intake. We studied 170 participants from the Isle of Wight 3rd Generation Cohort, UK. Phenotype data and exposure was assessed by questionnaires. Genome-wide DNA-M in cord blood samples was quantified using the Illumina Infinium HumanMethylation450 and EPIC Beadchips. Five SNPs (single-nucleotide polymorphisms) in the FADS gene cluster and one SNP in ELOVL5 were genotyped in offspring. FADS gene expression in offspring cord blood was determined.ResultsGestational fish intake was significantly associated with increased methylation of cg12517394 (P = 0.049), which positively correlated with FADS1 mRNA levels (P = 0.021). ELOVL5 rs2397142 was significantly associated with eczema (P = 0.011) and methylation at cg11748354 and cg24524396 (P < 0.001 and P = 0.036, respectively). Gestational fish intake was strongly associated with elevated DNA-M at cg11748354 and cg24524396 (P = 0.029 and P = 0.002, respectively) and reduced ELOVL5 mRNA expression (P = 0.028).ConclusionThe association between induced FADS1/2 and ELOVL5 DNA-M and reduced gene expression due to gestational fish intake provide a mechanistic explanation of the previously observed association between maternal LCPUFA intake and allergy development in early childhood.

Dietary pattern regulates fatty acid desaturase 1 gene expression in Indian pregnant women to spare overall long chain polyunsaturated fatty acids levels.

The aim of this study was to determine if the dietary pattern of pregnant women has any compensatory effect on the fatty acid desaturase (FADS) gene expression, thus enhancing the conversion of precursors to long chain polyunsaturated fatty acids (LCPUFA) to spare the overall LCPUFA levels. The dietary intake of plant-based precursor polyunsaturated fatty acids (PUFA) influences circulating levels of LCPUFA. We hypothesized that low LCPUFA diets during pregnancy would compensate by higher expression of FADS genes to enhance the conversion of precursors to LCPUFA to spare the overall LCPUFA levels. Seventy-five pregnant women were enrolled during the last trimester of pregnancy based on the eligibility and exclusion criteria. Maternal LCPUFA in plasma, expression of FADS1 and FADS2 genes, FADS2 Indel genotype status and neonate birth weight were studied.In the vegetarian group (n = 25), plasma α-linolenic acid (ALA) but not linoleic acid (LA) was significantly lower (p < 0.05) than the non-vegetarian group (n = 50). No significant differences were found for arachidonic acid (AA) or docosahexaenoic acid (DHA) levels. FADS1 expression was significantly higher in the vegetarian group compared to the non-vegetarian group. There was no significant difference in the birth weight of the neonates between two groups. No significant correlation was observed between FADS2 Indel genotype and birth weight. Our small sample size study demonstrated an increase FADS1expression during pregnancy in vegetarian pregnant women that may have contributed to the maintenance of AA, eicosapentaenoic acid and DHA levels thereby ensuring that the overall LCPUFA levels of the neonate is not compromised.

Associations between maternal long-chain polyunsaturated fatty acid concentrations and child cognition at 7 years of age: The MEFAB birth cohort

IntroductionConcentrations of the fish fatty acids EPA and DHA are low among Dutch women of reproductive age. As the human brain incorporates high concentrations of these fatty acids in utero, particularly during third trimester of gestation, these low EPA and DHA concentrations may have adverse consequences for fetal brain development and functioning. MethodsAnalyses were conducted using longitudinal observational data of 292 mother-child pairs participating in the MEFAB cohort. Maternal AA, DHA, and EPA were determined in plasma phospholipids - obtained in three trimesters - by gas-liquid chromatography. Cognitive function was assessed at 7 years of age, using the Kaufman Assessment Battery for Children, resulting in three main outcome parameters: sequential processing (short-term memory), simultaneous processing (problem-solving skills), and the mental processing composite score. Spline regression and linear regression analyses were used to analyse the data, while adjusting for potential relevant covariates. ResultsOnly 2% of the children performed more than one SD below the mental processing composite norm score. Children with lower test scores (<25%) were more likely to have a younger mother with a higher pre-gestational BMI, less likely to be breastfed, and more likely to be born with a lower birth weight, compared to children with higher test scores (≥25%). Fully-adjusted linear regression models did not show associations of maternal AA, DHA, or EPA status during any of the pregnancy trimesters with childhood sequential and simultaneous processing. ConclusionMaternal fatty acid status during pregnancy was not associated with cognitive performance in Dutch children at age 7.

Prepartum maternal diets supplemented with oilseeds alter the fatty acid profile in bovine neonatal plasma possibly through reduced placental expression of fatty acid transporter protein 4 and fatty acid translocase.

In the present study, we determined the effects of maternal dietary fat and the type of fat on plasma fatty acids and the expression of placental fatty acid transporter genes. In Experiment 1, Holstein cows in the last 35 days of gestation received diets containing sunflower seed (n=8; high in linoleic acid (LA)), canola seed (n=7; high in oleic acid (OLA)) or no oilseed (n=7; control). Fatty acids were quantified in dam and neonate plasma at calving. In Experiment 2, placental cotyledons were collected (LA: n=4; OLA: n=4; control: n=5) to quantify gene expression. Maternal long-chain polyunsaturated fatty acids, neonatal total n-3 fatty acids and eicosapentaenoic acid (EPA) declined, whereas docosahexaenoic acid (DHA) and total fat tended to decline following fat supplementation prepartum. Feeding of LA versus OLA prepartum tended to increase peroxisome proliferator-activated receptor α (PPARA) expression, whereas peroxisome proliferator-activated receptor δ (PPARD) and peroxisome proliferator-activated receptor γ (PPARG) expression tended to be higher in OLA- than LA-fed cows. Expression of fatty acid transporter protein 4 (FATP4) and fatty acid translocase (FAT/CD36) expression was lower in placental tissue of cows fed fat compared with control cows. Reduced total n-3 fatty acids, EPA and DHA in neonates born of dams fed fat prepartum is likely due to changes in PPARs and reduced expression of placental FATP4 and FAT/CD36.

Reduction of the n–6:n–3 long-chain PUFA ratio during pregnancy and lactation on offspring body composition: follow-up results from a randomized controlled trial up to 5 y of age1–3

It has been hypothesized that the n-6:n-3 (ω-6:ω-3) long-chain polyunsaturated fatty acid (LCPUFA) ratio in the maternal diet during the prenatal and early postnatal phase positively affects the body composition of the offspring. However, only limited data from prospective human intervention studies with long-term follow-up are available. We assessed the long-term effects of a reduced n-6:n-3 LCPUFA ratio in the diets of pregnant and lactating women [1020 mg docosahexaenoic acid (DHA) plus 180 mg eicosapentaenoic acid (EPA)/d together with an arachidonic acid-balanced diet compared with a control diet] on the body weights and compositions of their offspring from 2 to 5 y of age with a focus on the 5-y results. Participants in the randomized controlled trial received follow-up assessments with annual body-composition measurements including skinfold thickness (SFT) measurements (primary outcome), a sonographic assessment of abdominal subcutaneous and preperitoneal fat, and child growth. In addition, abdominal MRI was performed in a subgroup of 5-y-old children. For the statistical analysis, mixed models for repeated measures (MMRMs) were fit with the use of data from each visit since birth (except for MRI). Maternal LCPUFA supplementation did not significantly influence the children's sum of 4 SFTs [means ± SDs at 5 y of age: intervention, 23.9 ± 4.7 mm (n = 57); control, 24.5 ± 5.0 mm (n = 55); adjusted mean difference, -0.5 (95% CI: -2.2, 1.2)], growth, or ultrasonography measures at any time point in the adjusted MMRM model (all P values < 0.05). Results were consistent with abdominal MRI measurements (n = 44) at 5 y of age, which showed no significant differences in subcutaneous and visceral adipose tissue volumes and ratios. The current study provides no evidence that a dietary reduction of the n-6:n-3 LCPUFA ratio in the maternal diet during pregnancy and lactation is a useful early preventive strategy against obesity at preschool age. This trial was registered at clinicaltrials.gov as NCT00362089.

Optimal nutrition in lactating women and its effect on later health of offspring: A systematic review of current evidence and recommendations (EarlyNutrition project)

ABSTRACTBackground: EarlyNutrition (www.project-earlynutrition.eu) is an international research consortium investigating the effects of early nutrition on metabolic programming. Objective: To summarize current evidence and standards, recommendations, guidelines, and regulations on nutrition or supplements in lactating women with emphasis placed on long-term health effects in offspring, including cardiovascular disease, hypertension, overweight/obesity, metabolic syndrome, diabetes, or glucose intolerance. Methods: Medline, Embase, selected databases and websites were searched for documents published between 2010 and 2015. Results: Thirteen documents met the inclusion criteria. Effects of maternal long-chain polyunsaturated fatty acid (LC-PUFA) supplementation on overweight/obesity or hypertension in offspring were assessed in 10 studies. One study described the effect of maternal vitamin D supplementation on overweight/obesity, and the remaining 2 studies assessed the effects of maternal probiotic/synbiotic supplementation during lactation on overweight/obesity or metabolic syndrome in their infants. Forty-one documents contained dietary recommendations on various macro- and micronutrients for lactating women, but without consideration of our long-term health outcomes in infants. Conclusion: Literature on nutrition of lactating women and its effect on their infants' later health with respect to metabolic programming outcomes appeared to be scarce, and focused mostly on supplementation of LC-PUFA's. No recent guidelines or recommendations were available, highlighting the significant research gaps regarding this topic.

Red blood cell long-chain polyunsaturated fatty acid (LC-PUFA) levels in pregnant women predict length of gestation via effects on sleep quality and inflammation

Objective Mechanistic pathways linking maternal long-chain polyunsaturated fatty acid (LC-PUFA) status with gestational length are poorly delineated. Key LC-PUFAs implicated in this association are the antiinflammatory omega-3 docosahexaenoic acid (DHA) and proinflammatory omega-6 arachidonic acid (AA). We hypothesized that (1) lower red blood cell (RBC) DHA:AA ratios would predict shorter gestation and (2) this effect would be mediated by both inflammation and sleep quality. Methods Pregnant women (n = 135) provided blood and completed the Pittsburg Sleep Quality Index at 20–27 weeks gestation. RBC fatty acids were determined by gas chromatography and serum inflammatory markers (IL-6, IL-8, TNF- α , IL-1 β , CRP) were determined by high-sensitivity ELISA. Results Lower DHA:AA ratios predicted higher serum IL-8 (r = −0.20, p = 0.02) and poorer sleep quality (b = −13.8, p = 0.02). These relationships remained after adjusting for depressive symptoms, age, BMI, income, race, and smoking. Mediational analyses demonstrated indirect effects linking lower RBC DHA:AA with shorter gestation via higher IL-8 (95% CI = 0.10, 3.84) and poor sleep (95% CI = 0.35, 3.99). A significant race X DHA:AA interaction in predicting preterm birth (PTB) was observed (p = 0.049); among African Americans only, the odds of PTB decreased significantly as DHA:AA increased (OR for 0.1 unit increase = 0.25 (95% CI = 0.06, 0.99, p = 0.048). Discussion These data support both inflammatory pathways and sleep quality as significant mediators linking maternal DHA:AA status and length of gestation. African Americans may be at greater risk for PTB related to suboptimal DHA levels.

Potential programming of selected cardiometabolic risk factors at childhood by maternal polyunsaturated fatty acid availability in the MEFAB cohort

BackgroundIncreasing evidence suggests that long-chain polyunsaturated fatty acid (LCPUFA) availability in utero could program later health. ObjectiveThe objective of the study was to explore whether prenatal LCPUFA availability could be involved in programming cardiometabolic disease risk at childhood. MethodsData of 242 mother–child pairs from the Maastricht Essential Fatty Acid Birth (MEFAB) cohort were used. Multi-variable linear regression analysis was applied to identify associations between maternal LCPUFA concentrations around weeks 11, 22 and 32 of pregnancy and at time of delivery and cardiometabolic risk factors of their children (glucose metabolism, blood lipids, and blood pressure) at age 7. ResultsMaternal eicosapentaenoic acid (20:5n−3) at week 11 of pregnancy was negatively associated with children׳s glucose (B=−0.34mmol/L; 95% CI: −0.56, −0.12). Positive associations were found between maternal linoleic acid (18:2n−6) at time of delivery and children׳s proinsulin (B=0.25pmol/L; 95% CI: 0.08, 0.41); maternal 3-docosapentaenoic acid (22:5n−3) at week 11 and children׳s total cholesterol (B=1.23mmol/L; 95% CI: 0.45, 2.01) and low-density-lipoprotein cholesterol (B=1.12mmol/L; 95% CI: 0.42, 1.82); and maternal osbond acid (22:5n−6) at week 22 and tetracosadienoic acid (24:2n−6) at week 32 and children׳s diastolic blood pressure (B=16.86mmHg; 95% CI: 7.63, 26.08 and B=17.75mmHg; 95% CI: 6.37, 29.94, respectively). ConclusionOur findings suggest that maternal omega-6 (n−6) fatty acids may be of particular importance in relation to children׳s glucose metabolism and blood pressure, whereas omega-3 (n−3) fatty acids seem particularly related to blood lipids at childhood. In general, the strength of the associations appeared stronger with fatty acid concentrations in early pregnancy compared to late pregnancy.

Maternal LC-PUFA status during pregnancy and child problem behavior: the Generation R Study.

Omega 3 (n-3) and 6 (n-6) long-chain polyunsaturated fatty acids (LC-PUFAs) and the n-3:n-6 ratio are important for brain development. Whether maternal LC-PUFA status during pregnancy affects risk of problem behavior in later childhood is unclear. Within a population-based cohort, we measured maternal plasma docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and arachidonic acid (AA) concentrations and n-3:n-6-ratio in mid-pregnancy. Child emotional and behavioral problems at 6 y of age were assessed by parents (child behavior checklist), teachers (teacher report form), and combined parent/teacher report. Higher maternal DHA and n-3:n-6 ratio were associated with fewer child emotional problems using parent (odds ratio (OR)DHA = 0.82; 95% confidence interval (CI): 0.70, 0.96; P = 0.02 and OR(n-3:n-6) = 0.83; 95% CI: 0.71, 0.96; P = 0.01; n = 5,307) and combined parent/teacher scores (ORDHA = 0.79; 95% CI: 0.66, 0.95; P = 0.01 and OR(n-3:n-6) = 0.77; 95% CI: 0.65, 0.92; P < 0.01; n = 2,828). Higher AA was associated with more child behavioral problems using teacher (OR = 1.10; 95% CI: 1.00, 1.20; P = 0.04; n = 3,365) and combined parent/teacher scores (OR = 1.12; 95% CI: 1.02, 1.22; P = 0.02; n = 2,827). Maternal EPA was not associated with child problem behavior. Indications of associations of maternal LC-PUFA status with child emotional and behavioral problems were found. Future research is needed to identify LC-PUFA-sensitive periods of fetal brain development by including multiple assessments of prenatal LC-PUFA status.

The effect of long-chain polyunsaturated fatty acids intake during pregnancy on adiposity of healthy full-term offspring at birth.

The adjusted effect of long-chain polyunsaturated fatty acid (LCPUFA) intake during pregnancy on adiposity at birth of healthy full-term appropriate-for-gestational age neonates was evaluated. In a cross-sectional convenience sample of 100 mother and infant dyads, LCPUFA intake during pregnancy was assessed by food frequency questionnaire with nutrient intake calculated using Food Processor Plus. Linear regression models for neonatal body composition measurements, assessed by air displacement plethysmography and anthropometry, were adjusted for maternal LCPUFA intakes, energy and macronutrient intakes, prepregnancy body mass index and gestational weight gain. Positive associations between maternal docosahexaenoic acid intake and ponderal index in male offspring (β=0.165; 95% confidence interval (CI): 0.031-0.299; P=0.017), and between n-6:n-3 LCPUFA ratio intake and fat mass (β=0.021; 95% CI: 0.002-0.041; P=0.034) and percentage of fat mass (β=0.636; 95% CI: 0.125-1.147; P=0.016) in female offspring were found. Using a reliable validated method to assess body composition, adjusted positive associations between maternal docosahexaenoic acid intake and birth size in male offspring and between n-6:n-3 LCPUFA ratio intake and adiposity in female offspring were found, suggesting that maternal LCPUFA intake strongly influences fetal body composition.

Differential levels of long chain polyunsaturated fatty acids in women with preeclampsia delivering male and female babies

Maternal long chain polyunsaturated fatty acids (LCPUFA) play a key role in fetal growth and development. This study for the first time examines the maternal and cord LCPUFA levels in preeclamptic mothers delivering male and female infants. In this study 122 normotensive control pregnant women (gestation≥37 weeks) and 90 women with preeclampsia were recruited. Results indicate lower maternal plasma docosahexaenoic acid (DHA) levels (p<0.05) in women with preeclampsia delivering male babies as compared to normotensive control women delivering male babies. Similarly, cord nervonic acid levels were lower (p<0.01) in women with preeclampsia delivering male babies as compared to normotensive control group. However, cord nervonic acid levels were comparable in women with preeclampsia and normotensive control women delivering female babies. This data suggests that male babies born to mothers with preeclampsia may be at an increased risk of developing neurodevelopmental disorders as compared to female babies. Future studies need to follow up both male and female children born to mothers with preeclampsia since altered levels of LCPUFA at birth may have differential implications for the growth and development.

Prenatal exposure to methylmercury and LCPUFA in relation to birth weight

BackgroundEpidemiologic studies have been inconclusive regarding the impact of coexposure to long chain polyunsaturated fatty acids (LCPUFA) and methylmercury (MeHg) from fish consumption during pregnancy on measures of fetal development. ObjectivesWe evaluated the association between birth weight and prenatal maternal LCPUFA status and MeHg exposure in the Republic of Seychelles. MethodsWe measured LCPUFA in maternal whole blood collected at 28 weeks of gestation and following delivery and MeHg in maternal hair obtained at delivery. There were 230 births with complete data on birth weight and covariates. Multiple linear regression models controlled for infant sex, gestational age, maternal age, smoking during pregnancy, intrapartum weight gain, prepregnancy body mass index, maternal socioeconomic status, parity, gestational diabetes, and alcohol use during pregnancy. ResultsThe average birth weight was 3252 g (range 1654–4450) and the average gestational age was 39 weeks (range 34–41). Prenatal MeHg exposure and maternal LCPUFA status were not associated with birth weight. Infant sex and length of gestation were the only predictors, with male sex and increased gestational age consistently associated with greater birth weight. ConclusionsThese findings do not support a relationship between prenatal exposure to LCPUFA and/or MeHg from fish consumption and birth weight.