An example of using data from multiple longitudinal studies to address a scientific hypothesis:...

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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 Group School of Food Science & Nutrition

Transcript of An example of using data from multiple longitudinal studies to address a scientific hypothesis:...

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

Thank you

[email protected]

Nutritional Epidemiology GroupSchool of Food Science & Nutrition