Normal Plasma Volume Expansion and Micronutrient Status in Pregnancy

Abstract

Plasma volume expansion is widely known as an important physiologic change in pregnancy, yet normal expansion in healthy pregnancies has not been well described. This expansion influences plasma micronutrient concentrations and may impact interpretation of biomarkers. Our objective was to review studies that measured plasma volume longitudinally across gestation to describe normal plasma volume expansion; secondarily, we examined the impact of plasma volume expansion on micronutrient biomarkers. We systematically searched PubMed for original articles that directly measured plasma volume in pregnant women at more than one time across gestation. We also searched reference lists from these publications for additional papers. We found 15 studies published from 1963 to 2006 that directly measured plasma volume in pregnancy more than one time. We excluded 3 studies because the measurements were not longitudinal and one study because it used an unconventional measurement technique (iron dextran) and some values appeared extreme. Of the 11 longitudinal studies included, 8 studies were conducted in the UK and one each was conducted in India, Chile, and Nigeria. All studies used the Evans blue dye (T‐1824) indicator dilution method to measure the plasma volume. The total number of women in all studies was 524; study size ranged from 11 to 95. Plasma volume was measured 3 to 7 times in women across the studies. Two studies measured plasma volume before conception and 5 studies measured postpartum values (6–8 weeks after birth) as a proxy for pre‐conception. Plasma volume increases varied across the studies. Plasma volume increased by 8% between preconception and 12 weeks, 18% by 16 weeks, 27% by 20 weeks and 36% by 25 weeks gestation. The maximum mean plasma volume increase was 52% (1267 ± 38 ml) at 33–34 weeks gestation. This peak mean expansion ranged from 48% to 59% (1218 to 1323 ml) across studies, while reports of expansion for individual women ranged from 25% to 80%. Plasma volume slightly declined from late third trimester to term. Only one plasma volume study measured micronutrient status. In that study, plasma zinc concentrations declined across gestation to 30 weeks but intravascular zinc mass (the product of zinc concentration and plasma volume) increased across pregnancy. Plasma copper concentration increased up to gestational week 35 but intravascular copper mass was not reported. Few studies have measured plasma volume longitudinally in pregnancy. Studies of healthy pregnancies similarly show plasma volume increases progressively to approximately 52% above the non‐pregnant state in the third trimester with a slight decline to term. Plasma zinc concentration changes in pregnancy did not reflect actual changes in zinc status. Future studies in pregnancy should measure plasma volume to have a valid estimation of micronutrient status and to understand underlying physiologic changes that may be related to adverse outcomes.Support or Funding InformationNIH BIRCWH 12HD055882 (Dr. Gernand)