Effects of pre- versus post-conceptional iron and n-3 fatty acid supplementation of deficient rat dams on neurodevelopmental outcomes in the offspring

Abstract

This abstract was awarded the Student Competition Prize.Periconception is the period spanning the weeks directly before and after conception and is a crucial window for optimising neurodevelopment in offspring(1-4). Iron and omega-3 fatty acids (n-3 FAs) are two vital nutrients for the development of the nervous system however, little research has been conducted into their importance during the periconceptional window(5-8). This study investigated whether supplementing iron and n-3 FA deficient (ID and n-3 FAD) rat dams before conception compared to after conception results in different neurodevelopmental outcomes in offspring. We hypothesised that initiating iron and n-3 FA supplementation in deficient dams after conception would not be as efficacious in preventing impaired offspring neurodevelopment induced by double- deficiency, compared to initiating supplementation before conception.Female rats consuming an ID and n-3 FAD diet were randomly allocated to receive iron and DHA/EPA supplementation either 10 days before (Pre-Fe+DHA/EPA) or 10 days after conception (Post-Fe+DHA/EPA). Dams and offspring (Pre-: n = 24; Post-: n = 26) were subsequently maintained on supplemented diets throughout the experiment. Between postnatal days 31–41, cognitive and behavioural tests were conducted on offspring. Offspring were euthanised between postnatal day 42–45 and n-3 FAs, iron and monoamine concentrations were measured in the hippocampus, striatum and frontal cortex. All outcomes were compared to offspring who were either iron and n-3 FA deficient (ID+n-3 FAD: n = 24) or sufficient (Control+Fe+DHA/EPA: n = 22). One-way ANCOVA, with sex as a covariate, was used to determine between-group differences and two-way ANOVA was used to explore diet-sex interactions.There were no differences in brain iron or n-3 FA levels between Pre- and Post-Fe+DHA/EPA offspring (P > 0.05). Female Post-Fe+DHA/EPA offspring had greater norepinephrine concentrations in the frontal cortex (Pre-: 3.21 ± 0.57 ng/mg vs Post-: 2.50 ± 0.55 ng/mg; P = 0.014) and consumed less sucrose in the sucrose preference test (Pre-: 96.16 ± 1.73%; Post-: 90.15 ± 1.66%; P = 0.010) compared to Pre-Fe+DHA/EPA offspring. Female Post-Fe+DHA/EPA offspring also had significantly lower liver iron concentrations compared to female Pre-Fe+DHA/EPA offspring (Pre-: 537 ± 47.13 μg/L vs Post-: 310 ± 45.28 μg/L; P = 0.034). There were no other significant differences in monoamine concentrations or behavioural tests.Our results indicate that supplementing ID and n-3 FAD mothers both before and after conception is efficacious in preventing neurodevelopmental deficits associated with deficiency. However, ID and n-3 FAD during the periconceptional period may alter reward-based learning in female offspring(9-11). Additionally, optimising iron provision during periconception may have important implications for the prevention of postnatal ID-anaemia, particular during early infancy(12).