1. An example of using data from multiple longitudinal studies to address a scientific hypothesis: Maternal iron in pregnancy and offspring’s cardiovascular risk Dr Nisreen Alwan Wellcome Trust Clinical Research Fellow Nutritional Epidemiology Group School of Food Science & Nutrition

2. Background Nutritional Epidemiology Group School of Food Science & Nutrition Iron deficiency is a common problem during pregnancy No solid evidence to support routine iron supplementation programmes during pregnancy in relation to offspring outcomes Maternal nutrition during pregnancy is potentially linked to chronic disease risk in the offspring

3. Maternal iron deficiency during pregnancy and offspring health: findings from animal studies Nutritional Epidemiology Group School of Food Science & Nutrition McArdle et al (2006). Fetal programming: causes and consequences as revealed by studies of dietary manipulation in rats – a review. Placenta (27): 56-60.

4. Hypothesis Maternal iron deficiency during pregnancy is linked to increased cardiovascular risk in the offspring Nutritional Epidemiology Group School of Food Science & Nutrition

5. Aim Assess the relationship between maternal iron status / intake during pregnancy and both short-term and long-term cardiovascular risk indicators in the offspring Nutritional Epidemiology Group School of Food Science & Nutrition

7. 36/5228/52 Conception 1274 low-risk pregnancies in Leeds: 2003-06 12-18/52 Recruitment 24-hour recall Delivery CAT1CAT2CAT3 Letter of invitation

8. The CARE study Nutritional Epidemiology Group School of Food Science & Nutrition Dietary iron intake <UK RNI (14.8 mg/day) = 80% – More likely to be younger, lower socioeconomic profile – Less likely to take supplements during the 1 st trimester 24%, 15% & 8% took iron-containing supplements in 1 st, 2 nd & 3 rd trimester Total iron intake from diet and supplements associated with customised birthweight centile (adjusted change = 2.5 centiles/10 mg, 95% CI: 0.4, 4.6) Alwan, NA et al (2011). Dietary iron intake during early pregnancy and birth outcomes in a cohort of British women. Human Reproduction, 26, 911.

9. UKWCS (Iron and blood pressure study) Nutritional Epidemiology Group School of Food Science & Nutrition UKWCS – 1 st phase 35,372 women 35-69 years at recruitment across UK, 2 nd phase 15,000 C282Y is a common mutation (around 13% of Europeans), homozygotes more likely to develop haemochromatosis C282Y heterozygotes are asymptomatic but less likely to be iron-deficient C282Y used as an instrument for the exposure of interest (maternal iron status) to control for confounding

10. Nutritional Epidemiology Group School of Food Science & Nutrition Study design Mendelian randomisation Target sample – mothers 1416 mothers (716 C282Y carrier, 700 wild-type) Target sample - children 3376 Children (1686 of C282Y mothers, 1690 of wild-type mothers) Response 517 gave consent (17%) 348 Completed the study (10%) UKWCS (Iron and blood pressure study)

11. Pulse wave velocity is a strong predictor of CVD mortality in adults, and has been linked to CV risk factors such as lipids, body fat, blood pressure & glucose in children Retrospective cohort design Outcome – Neonatal arterial stiffness (Brachio-femoral PWV) Exposure – body iron stores in early pregnancy (serum transferrin receptor /serum ferritin) Nutritional Epidemiology Group School of Food Science & Nutrition Vicorder kit

12. Exposures: maternal dietary intake at 32 weeks gestation (FFQ), maternal supplement intake during pregnancy, maternal haemoglobin during pregnancy, cord ferritin Outcomes: Offspring’s pulse wave velocity and flow mediated dilatation at 10-12 years Potential mediators: maternal BMI, gestational age, birthweight, offspring dietary iron intake (FFQ) Nutritional Epidemiology Group School of Food Science & Nutrition ALSPAC

14. Thank you n.alwan@leeds.ac.uk Nutritional Epidemiology Group School of Food Science & Nutrition