A Perinatal Strategy For Preventing Adult Disease: The Role Of Long-Chain Polyunsaturated Fatty Acids

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In women with both milder and more severe hyperglycemia, n-3 LCPUFA may be acting as insulin-sensitizing agents 27 , reducing maternal hyperglycemia and subsequent fetal hyperinsulinemia driving adiposity accumulation in the offspring The general lack of associations in offspring of women with GDM and GIGT, which are more progressive states of maternal glucose intolerance, may be due monitoring or treatment of these women as well as dietary or medical interventions altering the level of n-3 LCPUFA or hyperglycemia. However, treatment guidelines during the enrollment period generally did not include GIGT, although this does not preclude that decisions on monitoring or treatment were taken by individual healthcare providers.

It should also be noted that both groups had small sample sizes. More well-powered dietary studies of these women and their offspring would further clarify the function of nutritional agents in mitigating adverse metabolic outcomes in the offspring. There were some limitations to this study. Sample size was small for the models evaluating cord blood measures with some of the outcome biomarkers.

However, the strongest associations were still found for cord blood, suggesting a lower exposure measurement error or more proximate exposure to the developing fetus. Nutrient intake reported in the FFQ is subject to measurement error, although the error is more likely to be non-differential given the prospective nature of the study. As such non-differential measurement error would attenuate the effect estimates toward the null. Maternal fatty acids were assessed only in second trimester and we can therefore not rule out effects earlier in pregnancy.

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While most fetal growth takes place in second and third trimesters and may be more important for anthropometric outcomes, much of the organ architecture is laid down earlier in pregnancy and nutritional influences during this time period may affect physiology. We did not have DXA measurements for early childhood and were not able to directly compare DXA body composition measures between the two time points.

The collected data included detailed prospective information on many covariates, including maternal education, pre-preegnancy BMI, smoking, and glucose tolerance status.

However, we cannot exclude the possibility of residual confounding. This study included numerous exposure and outcome associations, raising the likelihood of chance findings due to multiple comparisons. Instead of imposing a conservative correction for multiple testing we looked for consistency and strength in findings, as well as biological plausibility. There were some differences in maternal sociodemographic and lifestyle covariates, but not exposures, between mothers with and without outcome data, pointing to limited selection bias.

Project Viva participants had health insurance, and many were lege-educated There were several strengths to this study. The prospective, longitudinal design allowed for the comprehensive study of prenatal fatty acid status in relation to cardiometabolic outcomes at two time points in childhood. With outcome data in both early and mid-childhood we could examine whether prenatal effects persisted across a relatively short time period.

We included biomarker measures of the exposure as well as of intake to examine whether associations with biomarkers translated to findings in maternal intake. While intake may be more relevant for making recommendations, biomarkers are closer to the physiological pathways of interest. We had detailed outcome data that were measured objectively rather than self-reported and allowed us to examine a broader cardiometabolic profile that included not only classical risk factors such as adiposity, HOMA-IR, and BP but also adipokines.

A perinatal strategy to prevent adult diseases: The role of long-chain polyunsaturated fatty acids

In this study, we found that higher umbilical cord plasma DHA was associated with lower offspring BMI z -scores, waist circumference, and leptin level in early, but not in mid-childhood. These associations tended to be stronger among offspring born to mothers with isolated hyperglycemia. This study supports early, limited, and potentially transient effects of prenatal n-3 LCPUFA status on offspring metabolic health, but longitudinal studies of offspring are needed to clarify effects that may emerge over time.

Further dietary studies of mother—offspring dyads exposed to prenatal hyperglycemia are warranted. Juturu, V. Omega-3 fatty acids and the cardiometabolic syndrome. Maternal dietary fat determines metabolic profile and the magnitude of endocannabinoid inhibition of the stress response in neonatal rat offspring. Endocrinology , — Hollander, K. Dietary enrichment with alpha-linolenic acid during pregnancy attenuates insulin resistance in adult offspring in mice.

Hussain, A. Acta Physiol. Sardinha, F. Sex-dependent nutritional programming: fish oil intake during early pregnancy in rats reduces age-dependent insulin resistance in male, but not female, offspring. Siemelink, M. Dietary fatty acid composition during pregnancy and lactation in the rat programs growth and glucose metabolism in the offspring. Diabetologia 45 , — Courville, A. Consumption of a DHA-containing functional food during pregnancy is associated with lower infant ponderal index and cord plasma insulin concentration. Much, D. Voortman T. Lucia Bergmann, R. Does maternal docosahexaenoic acid supplementation during pregnancy and lactation lower BMI in late infancy?

Campoy, C. Effects of prenatal fish-oil and 5-methyltetrahydrofolate supplementation on cognitive development of children at 6. Association between polyunsaturated fatty acid concentrations in maternal plasma phospholipids during pregnancy and offspring adiposity at age 7: the MEFAB cohort. Prostaglandins, Leukot. Fatty Acids 91 , 81—85 Helland, I. Pediatrics , e—e Moon, R. Maternal plasma polyunsaturated fatty acid status in late pregnancy is associated with offspring body composition in childhood. Rytter, D. Intake of fish oil during pregnancy and adiposity in y-old offspring: follow-up on a randomized controlled trial.

No association between the intake of marine n-3 PUFA during the second trimester of pregnancy and factors associated with cardiometabolic risk in the year-old offspring. Stein, A. Growth to age 18 months following prenatal supplementation with docosahexaenoic acid differs by maternal gravidity in Mexico. Fish oil supplementation during late pregnancy does not influence plasma lipids or lipoprotein levels in young adult offspring. Lipids 46 , — Hauner, H.

The role of dietary fatty acids for early human adipose tissue growth. Muhlhausler, B. Effect of long-chain polyunsaturated fatty acid supplementation during pregnancy or lactation on infant and child body composition: a systematic review. Rodriguez, G. Effect of n-3 long chain polyunsaturated fatty acids during the perinatal period on later body composition.

Effect of reducing the nn-3 long-chain PUFA ratio during pregnancy and lactation on infant adipose tissue growth within the first year of life: an open-label randomized controlled trial. Stratakis, N. Fish intake in pregnancy and child growth: a pooled analysis of 15 European and US birth cohorts. JAMA Pediatr.

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Yogev, Y. Obesity, gestational diabetes and pregnancy outcome. Fetal Neonatal Med. Clausen, T. Overweight and the metabolic syndrome in adult offspring of women with diet-treated gestational diabetes mellitus or type 1 diabetes. Regnault, N. Sex-specific associations of gestational glucose tolerance with childhood body composition. Diabetes Care. Oh, D. GPR is an omega-3 fatty acid receptor mediating potent anti-inflammatory and insulin-sensitizing effects. Cell , — Pagan, A. Materno-fetal transfer of docosahexaenoic acid is impaired by gestational diabetes mellitus.

Wijendran, V. Fetal erythrocyte phospholipid polyunsaturated fatty acids are altered in pregnancy complicated with gestational diabetes mellitus. Lipids 35 , — Maternal plasma phospholipid polyunsaturated fatty acids in pregnancy with and without gestational diabetes mellitus: relations with maternal factors.

Donahue, S. Prenatal fatty acid status and child adiposity at age 3 y: results from a US pregnancy cohort. Oken, E. Cohort profile: project viva.

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Fawzi, W. Calibration of a semi-quantitative food frequency questionnaire in early pregnancy. Associations of maternal prenatal dietary intake of n-3 and n-6 fatty acids with maternal and umbilical cord blood levels. Prostaglandins Leukot.

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Fatty Acids 80 , — Nutrient Data Laboratory Homepage. Willett, W. Nutritional Epidemiology 2nd edn Oxford Univ. Press, New York, Lin, Y. Automated high-throughput fatty acid analysis of umbilical cord serum and application to an epidemiological study. Lipids 47 , — Maternal prenatal fish consumption and cognition in mid childhood: Mercury, fatty acids, and selenium. Neurotoxicology Teratol. National Center for Health Statistics. Accessed 20 July Goran, M. Intra-abdominal adipose tissue in young children.

Shorr, I. Louer, A. Assessment of child anthropometry in a large epidemiologic study. Mueller, W. Human Kinetics Books, Champaign, 83— Chobanian, A. Hypertension 42 , — Matthews, D. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28 , — Cespedes, E. Longitudinal associations of sleep curtailment with metabolic risk in mid-childhood. Obesity Silver Spring. Obesity Silver Spring 22 , — Eisenmann, J. Construct validity of a continuous metabolic syndrome score in children.


Viitasalo, A. Validation of metabolic syndrome score by confirmatory factor analysis in children and adults and prediction of cardiometabolic outcomes in adults. Diabetologia 57 , — American Diabetes Association. Gestational diabetes mellitus. Diabetes Care 27 Suppl 1 , S88—S90 Food and Drug Administration. Available at www.

Accessed 6 May Olsen, S. Intake of marine fat, rich in n-3 -polyunsaturated fatty acids, may increase birthweight by prolonging gestation. Lancet 2 , — Chen, B. Fish oil supplementation improves pregnancy outcomes and size of the newborn: a meta-analysis of 21 randomized controlled trials. Further on the association between retarded foetal growth and adult cardiovascular disease. Could low intake or marine diets be a common cause?

Innis, S. Docosahexaenoic acid and arachidonic acid enhance growth with no adverse effects in preterm infants fed formula. Koletzko, B. Fatty acid profiles, antioxidant status, and growth of preterm infants fed diets without or with long-chain polyunsaturated fatty acids. A randomized clinical trial. Rump, P. Components of the insulin resistance syndrome in seven-year-old children: relations with birth weight and the polyunsaturated fatty acid content of umbilical cord plasma phospholipids. Standl, M. Associations of seafood and elongated n-3 fatty acid intake with fetal growth and length of gestation: results from a US pregnancy cohort.

Dabelea, D. Intrauterine exposure to diabetes conveys risks for type 2 diabetes and obesity: a study of discordant sibships. Diabetes 49 , — Silverman, B. Long-term prospective evaluation of offspring of diabetic mothers. Diabetes 40 Suppl. Voortman, T. Effects of polyunsaturated fatty acid intake and status during pregnancy, lactation, and early childhood on cardiometabolic health: a systematic review.

Lipid Res. Zhao, J. Circulating docosahexaenoic acid levels are associated with fetal insulin sensitivity. The effect of maternal fish oil supplementation during the last trimester of pregnancy on blood pressure, heart rate and heart rate variability in the year-old offspring.

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