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Plasma volume expansion is widely quoted as being 50% above the nonpregnant volume, as if this is a well-established value. Methods for measuring plasma volume are reviewed elsewhere. The concentration of the tracer is measured and used to back-extrapolate the concentration of dye at the time of complete mixing, allowing calculation of plasma volume. Most methods are indicator dilution techniques, requiring a blood draw, injection of a tracer (usually Evans blue dye or indocyanine green), and serial blood collection post-injection. Studies describing plasma volume expansion across gestation are limited, in part because measurements are costly and somewhat invasive. Diagnostic biomarkers could be misinterpreted due to abnormal plasma volume expansion. For instance, higher plasma volume has been associated with lower plasma zinc and folate concentrations but higher plasma copper and ceruloplasmin concentrations. However, the relationship between plasma volume and plasma-based biomarker concentrations may be complicated. Hemoglobin concentrations decrease as plasma volume increases to a greater extent than red blood cell mass, and diagnostic cut-offs for anemia vary by trimester. As well, plasma volume expansion affects blood-based biomarker concentrations during pregnancy. The increase in plasma volume has even been suggested to be more important than maternal stature in terms of its influence on birthweight. Plasma volume in the third trimester and total plasma volume expansion are both positively associated with birthweight. Adverse pregnancy outcomes, including hypertensive disorders of pregnancy, have been linked to reduced plasma volume expansion during pregnancy.
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Since that time, there have been additional studies of plasma volume, but not many. As with other physiologic changes during pregnancy that were not well understood or characterized, more knowledge was needed on the range of healthy plasma volume expansion in order to identify abnormal changes that could be part of a disease process. They serially measured plasma volume in the same group of women across pregnancy, and at varying times after pregnancy. In 1934, Dieckmann and Wegner’s formative paper on plasma volume crystalized our understanding that plasma volume increases substantially as part of normal pregnancy. Yet, there were conflicting reports about the nature of the expansion, in part because most studies were not longitudinal.
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Additional longitudinal studies are needed to better characterize the range of normal plasma volume expansion across maternal characteristics.Įarly in the twentieth century, there was emerging evidence that plasma volume increased during pregnancy.
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The patterns observed from these studies may not reflect the current population, partly due to the changes in BMI over the last several decades. In healthy pregnancies, plasma volume begins to expand in the first trimester, has the steepest rate of increase in the second trimester, and peaks late in the third trimester. Included studies were rated from moderate to high quality 7 out of 10 studies were conducted over 30 years ago. The highest rate of increase occurred in the first half of the second trimester. In the third trimester, plasma volume was increased by 42% (95% CI 38–46) in weeks 28–34 and 48% (95% CI 44–51) in weeks 35–38. In the second trimester, plasma volume was increased by 18% (95% CI 12–24) in gestational weeks 14–20 and 29% (95% CI 21–36) in weeks 21–27 above the nonpregnant state. Plasma volume increased by 6% (95% CI 3–9) in the first trimester compared to the nonpregnant state. Ten observational studies with a total of 347 pregnancies were eligible. We combined data across studies using a random effects model. PubMed, Web of Science, Cochrane, CINAHL, and databases were searched from the beginning of each database to February 2019. Specifically, we included studies that measured plasma volume at least two times across gestation and one time before or after pregnancy in the same women. We conducted a systematic review and meta-analysis to identify original studies that measured plasma volume in singleton pregnancies of healthy women. We aimed to evaluate the pattern of plasma volume expansion across healthy pregnancies from longitudinal studies. High or low expansion has been related to adverse pregnancy outcomes, yet there is a limited understanding of normal/healthy plasma volume expansion. Plasma volume expansion is an important physiologic change across gestation.