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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 GroupSchool of Food Science & Nutrition
Background
Nutritional Epidemiology GroupSchool 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
Maternal iron deficiency during pregnancy and offspring health: findings from animal studies
Nutritional Epidemiology GroupSchool 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.
Hypothesis
Maternal iron deficiency during pregnancy islinked to increased cardiovascular risk in the
offspring
Nutritional Epidemiology GroupSchool of Food Science & Nutrition
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 GroupSchool of Food Science & Nutrition
36/5228/52
Conception
1274 low-risk pregnancies in Leeds: 2003-06
12-18/52Recruitment
24-hour recall
Delivery
CAT1 CAT2 CAT3
Letter of invitation
The CARE studyNutritional Epidemiology GroupSchool 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 1st trimester
• 24%, 15% & 8% took iron-containing supplements in 1st, 2nd & 3rd 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.
UKWCS (Iron and blood pressure study)
Nutritional Epidemiology GroupSchool of Food Science & Nutrition
• UKWCS – 1st phase 35,372 women 35-69 years at recruitment across UK, 2nd 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
Nutritional Epidemiology GroupSchool of Food Science & Nutrition
Study desig
n
•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)
• 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 GroupSchool of Food Science & Nutrition
Vicorder kit
• 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 GroupSchool of Food Science & Nutrition
ALSPAC