Background

Maternal anemia during pregnancy has previously been reported to be associated with elevated offspring blood pressure in later life1;2. However, this has only been reported in a small number of studies, with others failing to replicate this association3-5. Indeed, we previously explored this in ALSPAC6 and did not observe any consistent relationship between indicators of maternal iron status and offspring blood pressure at 7 years. A potential limitation of such studies is that assessing maternal iron status from haemoglobin measures is complicated by the tendency for low antenatal haemoglobin levels to reflect the natural haemodilution of pregnancy, rather than being indicative of pathological iron deficiency anemia. As such, there may be limited ability to identify causal effects of maternal iron deficiency anemia within such studies and this may have contributed to the inconsistent associations previously observed. We would like to build on our previous work carried out in ALSPAC by a) exploring maternal genetic variants affecting iron status as proxies for maternal iron, in order to better identify causal effects of maternal iron status and b) using trajectories of blood pressure across childhood and adolescence as the outcome measure, rather than one single measure of blood pressure. This will allow us to examine whether maternal iron status influences blood pressure across childhood or only at specific ages.

In contrast to the hypothesised adverse effects of maternal anemia during pregnancy, some have argued that iron depletion during pregnancy might in fact represent an adaptive physiological condition to prevent the adverse effects of oxidation, insulin resistance and thrombosis7. Indeed, whether iron supplementation in pregnancy is necessary, or even toxic, is still controversial and there is some evidence that maternal iron supplementation in pregnancy is associated with adverse outcomes such as increased risk of gestational diabetes and hypertensive disorders of pregnancy7;8. Thus, in addition to studying trajectories of child blood pressure, we would also like to assess the relationship between genetic variation in maternal iron status and trajectories of maternal blood pressure during pregnancy and gestational diabetes/glycosuria in ALSPAC.

Research Questions:

1) Is maternal iron status in pregnancy (as indicated by maternal iron genotypes) causally associated with offspring baseline BP at age 7 and BP trajectories between ages 7 and 15 years?

2) Is maternal iron status in pregnancy (as indicated by maternal iron genotypes) causally associated with maternal BP trajectories in pregnancy? For these analyses women with existing hypertension will be excluded.

3) Is maternal iron status in pregnancy (as indicated by maternal iron genotypes) causally associated with maternal gestational diabetes/glycosuria? This combined outcome will be used because there are too few cases of gestational diabetes alone for meaningful analyses; the use of glycosuria is justified by previous research in ALSPAC showing that it is associated with macrosomia9. For these analyses mothers with existing diabetes will be excluded.

Reference List

(1) Law CM, Barker DJ, Bull AR, Osmond C. Maternal and fetal influences on blood pressure. Arch Dis Child 1991; 66(11):1291-1295.

(2) Godfrey KM, Forrester T, Barker DJ, Jackson AA, Landman JP, Hall JS et al. Maternal nutritional status in pregnancy and blood pressure in childhood. Br J Obstet Gynaecol 1994; 101(5):398-403.

(3) Whincup P, Cook D, Papacosta O, Walker M, Perry I. Maternal factors and development of cardiovascular risk: evidence from a study of blood pressure in children. J Hum Hypertens 1994; 8(5):337-343.

(4) Bergel E, Haelterman E, Belizan J, Villar J, Carroli G. Perinatal factors associated with blood pressure during childhood. Am J Epidemiol 2000; 151(6):594-601.

(5) Belfort MB, Rifas-Shiman SL, Rich-Edwards JW, Kleinman KP, Oken E, Gillman MW. Maternal iron intake and iron status during pregnancy and child blood pressure at age 3 years. Int J Epidemiol 2008; 37(2):301-308.

(6) Brion MJ, Leary SD, Davey Smith G, McArdle HJ, Ness AR. Maternal anemia, iron intake in pregnancy, and offspring blood pressure in the Avon Longitudinal Study of Parents and Children. Am J Clin Nutr 2008; 88(4):1126-1133.

(7) Bo S, Menato G, Villois P, Gambino R, Cassader M, Cotrino I et al. Iron supplementation and gestational diabetes in midpregnancy. Am J Obstet Gynecol 2009; 201(2):158-6.

(8) Ziaei S, Norrozi M, Faghihzadeh S, Jafarbegloo E. A randomised placebo-controlled trial to determine the effect of iron supplementation on pregnancy outcome in pregnant women with haemoglobin greater than or = 13.2 g/dl. BJOG 2007; 114(6):684-688.

(9) Lawlor DA, Fraser A, Lindsay RS, Ness A, Dabelea D, Catalano P et al. Association of existing diabetes, gestational diabetes and glycosuria in pregnancy with macrosomia and offspring body mass index, waist and fat mass in later childhood: findings from a prospective pregnancy cohort. Diabetologia 2010; 53(1):89-97.