Impact of long chain polyunsaturated fatty acids during pregnancy and lactation on infant body composition up to 5 years of life – Results of the INFAT-study Christina Brei*, Stefanie Brunner, Karina Pusch, Daniela Much, Lynne Stecher, Ulrike Amann-Gassner and Hans Hauner Else Kröner-Fresenius-Center for Nutritional Medicine, Chair of Nutritional Medicine, Technische Universität München, Georg-Brauchle Ring 60/62, 80992 Munich Background & Aim There is a strong need for the prevention of childhood overweight and obesity starting early in life. The ratio of long-chain polyunsaturated fatty acids (LCPUFAs) in the maternal diet may have an impact on offspring body composition. We investigated the effect of reducing the n-6/n-3 LCPUFA ratio in maternal diet during pregnancy and lactation on offspring growth and body composition from birth up to 5 years of life. Study Design & Methods 208 healthy pregnant women (pre-pregnancy BMI: 18-30 kg/m2) were randomly assigned to either a dietary intervention [supplementation with 1.2 g n-3 LCPUFAs as 3 fish oil capsules/day and dietary counseling to reduce arachidonic acid (AA) intake] from the 15th week of gestation until 4 months postpartum or to a control group, receiving general recommendations on a healthy diet. Skinfold thickness (SFT) measurements as primary outcome, abdominal ultrasonography (US) and other anthropometric measurements were determined at study visits (1). To investigate long-term effects, a follow-up program up to 5 years was initiated (Figure 1). 2006: Study start 2014: End of follow-up Randomization Intervention: Supplementation with n-3 LCPUFAs and dietary counseling to reduce AA in the diet Abbreviations Maternal blood A = anthropometry SFT = skinfold thickness measurement US = ultrasonography wk gest. = weeks of gestation wk = week pp = postpartum Control: Recommendations for a healthy diet Blood infant 15th wk gest. 32nd wk gest. Delivery 6 wks pp 4 months pp 1 year pp 2 years pp 3 years pp 4 years pp 5 years pp Umbilical cord blood Placental tissue A+SFT A+SFT+US A+SFT+US A+SFT+US A+SFT+US A+SFT+US A+SFT+US A+SFT+US N=208 N=189 N=188 N=180 N=174 N=170 N=118 N=120 N=107 N=114 Figure 1: Study design and follow-up Results & Interpretation A total of 208 women of Caucasian origin, relatively well-educated, nonsmoking, with an average age of 32 years, and a mean prepregnancy BMI of 22 kg/m2 were enrolled in the study. Maternal clinical characteristics, diet, lifestyle factors, and sociodemographic variables of the 2 groups were comparable at baseline (data not shown). Compliance was confirmed by blood fatty acid composition/dietary records before and after intervention (data not shown) (2). Newborns in the intervention group showed a higher weight and growth indices at birth (weight-for length, BMI and ponderal index), which were caused by prolonged gestation (2). Differences disappeared and were not detectable at 6 weeks postpartum or at any other timepoint. Only BMI showed a significant difference between the groups in the adjusted model at 4 years of life with higher values in the intervention group [mean difference: 0.4 kg/m2 (95% CI: 0.0; 0.8 kg/m2); p=0.05] (data not shown), which was no longer present at 5 years of age. Longitudinal SFT measurements as primary outcome variable did not differ between groups at any of the 8 time points investigated, neither the 4 individual SFTs nor their calculated sum. Data for growth indices and body composition at 5 years of age are given in Table 1. a b Table 1 Growth indices and body composition at 5 years of age by study group Parameter Group N Mean ± SD Adjusted mean difference (95% CI) p Weight [kg] Intervention 58 19.2 ± 3.0 0. (-0.5; 1.5)1 0.338 Control 56 18.7 ± 2.1 Height [cm] 111.2 ± 4.8 0.5 (-1.1; 2.2)1 0.522 110.7 ± 4.0 BMI [kg/m2] 15.5 ± 1.4 0.2 (-0.3; 0.7)1 0.434 15.2 ± 1.1 Waist circ. [cm] 53.4 ± 5.2 0.5 (-1.1; 2.1)1 0.556 52.8 ± 2.9 Head circ. [cm] 51.2 ± 1.3 0.0 (-0.5; 0.5)1 0.990 Sum 4 SFT 57 23.9 ± 4.7 -0.7 (-2.5; 1.1)1 0.453 55 24.5 ± 5.0 Body fat [%] 17.9 ± 3.4 -0.0 (-1.3; 1.3)2 0.976 18.1 ± 3.6 Fat mass [g] 3502.9 ± 1140.4 113.1 (-275.6; 501.9)2 0.565 3406.1 ± 847.2 Lean body mass [g] 15781.3 ± 2060.8 305.6 (-409.6; 1020.8)2 0.399 15306.6 ± 1694.9 Figure 2 Development of abdominal subcutaneous (a) and preperitoneal (b) fat distribution by study groups assessed by ultrasonography Area sag sc = Area of subcutaneous fat in sagittal plane Area sag pp = Area of preperitoneal fat in sagittal plane Multiple regression analysis controlling for sex, pregnancy duration, PI at birth and breastfeeding status at 4 months, current weight, current height; * p < 0.05; ** p < 0.02; *** p < 0.001 Conclusion 1 Multiple regression analysis controlling for sex, pregnancy duration, PI at birth, breastfeeding status at 4 months 2 Multiple regression analysis controlling for pregnancy duration, PI at birth, breastfeeding status at 4 months Results from the present study and the current scientific view (3) indicate that a modification of dietary fatty acid intake during pregnancy and lactation seems not to be a reasonable strategy to limit adipose tissue growth and thereby prevent obesity in early life. Thickness of abdominal subcutaneous fat layers assessed by US differed significantly at 2, 4 and 5 years of age in the adjusted model, but not at 3 years of age, showing slightly more subcutaneous fat in the control group (Figure 2a). Preperitoneal fat was not significantly different in the two groups at any time point of investigation (Figure 2b). Literature 1) Hauner et al. (2009) Ann Nutr Metab. 54:97-103; 2) Hauner et al. (2012) AJCN. 95:383-394; 3) Hauner and Brunner (2015) Curr Opin Clin Nutr Metab Care. 18:113-117. Funding * Contact person: Christina Brei, M. Sc., christina.brei@tum.de The INFAT-study was funded by the Else Kröner-Fresenius-Foundation, Bad Homburg, the International Unilever Foundation, Hamburg, Danone Baby Nutrition Research, Friedrichsdorf, German Ministry of Education and Research, Competence Network Obesity, and the EU-Consortium EARNEST *Contact person: Christina Brei, M. Sc., christina.brei@tum.de