Supplementation of Omega-3 Fatty Acids During Pregnancy: Inflammation, Endocannabinoids, and Infant Adiposity

Non-Technical Summary:<br/>
Pregnancy makes it difficult for the body to regulate blood glucose (sugar) levels and this condition (insulin resistance) is worsened by excess weight and excessive weight gain in pregnancy. The insulin resistance during pregnancy is known to be accompanied by inflammation. Naturally occurring signaling lipids that help maintain reproductive health and regulate inflammation have been identified (endocannabinoids). Overweight or excessive weight gain in pregnancy affects the developing fetus during the pregnancy and can increase adiposity for the offspring and increase the risk for chronic diseases for the infant later in life. Our broad research hypothesis is that supplementing overweight pregnant women with omega 3 long chain polyunsaturated fatty acids (LCPUFAs), such as the fats found in cold water marine fish, will decrease inflammation and result in leaner infants and toddlers; the signaling lipids will be modulated (decreased for some, increased for others). The specific aims of this 3 year intervention trial are to assess, for women consuming omega 3 LCPUFAs versus a control oil (placebo) during pregnancy, beginning at 17 to 20 weeks of pregnancy: i) severity of inflammation; ii) maternal weight gain; and iii) infant and toddler body fatness at 2 wks and 6 and 12 months. To our knowledge, there has been no prior research focused on examining the effects of omega 3 LCPUFAs during pregnancy complicated by overweight on inflammation and infant and toddler fatness. The significance of this research is that we can expand on what is known about the effectiveness of omega 3 fatty acids on pregnancy outcome. We will be better positioned to make dietary recommendations to pregnant women and women of child bearing ages about the health benefits of omega 3 fatty acids in pregnancy.
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Approach:<br/>
Pregnant women (18 to 35 years, BMIs of 25.0 to 29.9 kilograms per meter squared) will be recruited from Woman's Hospital, Baton Rouge, LA. Exclusion criteria are: parity greater than 5, history of chronic hypertension, metabolic syndrome, polycystic ovary syndrome, hyperlipidemia, renal or liver diseases, thyroid disorder, multiple gestations or pregnancy induced complications [e.g., gestational diabetes mellitus (GDM), hypertension, preterm labor, premature rupture of the membranes, or advanced maternal age (36 years or greater)]. Women will be primiparous or will not have been pregnant or lactating for the past year. Design: Double blind placebo controlled trial. Neonatal evaluation: Neonatal data will be collected prospectively and will include the mode of delivery, birth weight, head circumference, physical exam, Apgar scores, size for age, ponderal index, maturity rating and classification, the development of neonatal hypoglycemia or hyperbilirubinemia and birth trauma. Sample Collections, Measurements and Analyses: Maternal and cord blood samples will be collected into EDTA vacutainer tubes. Plasma and red blood cells will be stored at 80 degrees C until analyses. Fatty acids: Fatty acids will be quantified by gas liquid chromatography (Hewlett Packard 5890) using established methods. Inflammatory markers: The following will be measured at PBRC's Clinical Chemistry Core Laboratory using enzyme linked immunosorbent assays (ELISA): adiponectin, TNF alpha, IL 6; radioimmunoassay will be used for CRP. Insulin (venous cord blood): Plasma insulin will be analyzed using the human insulin ELISA kit from Linco Research, Inc (St. Charles, MI). Endocannabinoids: Identification and Quantification: As established and detailed by our laboratory plasma samples and deuterated internal standards will be analyzed using a TSQ Quantum Ultra triple quadrupole mass spectrometer (Thermo Electron, San Jose, CA) with Aligent 1100 LC front end (Aligent Technologies, Wilmington, DE). Nutrient Composition will be assessed using the University of Minnesota Nutrition Data System for Research (NDSR). Infant Birth Weight (kg) and Length (cm): Infant body weight at birth (gm) will be obtained using a standard electrical scale. Infant and Toddler Body Composition at 2 weeks, 6 and 12 months: These determinations will be made using the PEA POD and the BOD POD with the Pediatric Option (Life Measurement, Inc., www.lifemeasurement.com). Statistical Analyses Outcomes: Maternal primary outcome measures: maternal plasma inflammatory markers and endocannabinoids, and red blood cell fatty acids levels [measured at 17 to 20 weeks (baseline), 24, 30 and 36 weeks]. Covariates for the maternal measures: maternal dietary omega 3 LCPUFAs, socioeconomic status, age, prepregnancy BMI, gestational age and gestational weight gain. Infant/toddler primary outcome measures: infant birth weight; cord venous insulin concentration; body composition at 2 weeks, 6 and 12 months. Covariates for infant measures: gestational age, maternal dietary omega 3 LCPUFA, socioeconomic status, maternal gestational weight gain, maternal prepregnancy BMI and gestational age.
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Progress:<br/>
2012/03 TO 2013/02<br/>
OUTPUTS: Agreement with a supplier for omega-3 and placebo capsules for the intervention has been made, and the capsules have been in production and are scheduled for delivery to the PI approximately 04/2013. The agreement between the capsule supplier and Pennington Biomedical Research Center is in the final stage of approval by the two parties. IRB approval for the study has been obtained from Woman's Hospital, Baton Rouge, LA, Pennington Biomedical Research Center, Baton Rouge, LA, and the Agricultural Center, Louisiana State University, Baton Rouge, LA. IRB approval is currently being reviewed for re-approval by all institutions. The PEA POD has been purchased and installed at Woman's Hospital. The staff has been trained for assessments of infant body composition. <br/>PARTICIPANTS: The PI (CJL-K) worked with IRB at Woman's Hospital, Baton Rouge and Pennington Biomedical Research Center, Baton Rouge for IRB approval. Staff at Woman's Hospital have been trained to conduct assessment of infant body composition using the PEA POD and by measurments of circumference and skinfolds.
<br/>TARGET AUDIENCES: Nothing significant to report during this reporting period.
<br/>PROJECT MODIFICATIONS: Not relevant to this project.
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IMPACT: The investigators have reviewed the option of using the BOD POD Pediatric Option for assessment of infant/toddler body composition when infants exceed the PEA POD's capability at body weights greater than 8 kg. Based on inability to validate the BOD POD Pediatric Option, we will rely on measurements using the PEA POD to its weight limit and make measurements of circumference and skinfold from 2 weeks to 12 months.