Normal reference ranges for laboratory values in pregnancy
- F Gary Cunningham, MD
F Gary Cunningham, MD
- Professor and Holder of Beatrice and Miguel Elias Distinguished Chair in Obstetrics and Gynecology
- University of Texas Southwestern Medical Center
Numerous physiological changes occur during pregnancy to accommodate the maternal and fetal needs. Most of these changes begin soon after conception and continue until late gestation. Not surprisingly, these physiologic adaptations of pregnancy result in many significant changes in laboratory test values. Some of these changes are well-known, such as the reduction in hematocrit and hemoglobin levels, which is termed physiological or dilutional anemia of pregnancy. Similarly, the renal changes leading to lower creatinine values in pregnancy are well-described and a "normal" serum creatinine value of 1.0 mg/dL in a nonpregnant woman is immediately recognized as elevated in the pregnant woman.
Despite the well-recognized phenomenon of pregnancy-induced physiological changes and their potential for altering normal laboratory values, very few laboratories provide clinicians with normal reference ranges during pregnancy. Indeed, many laboratories do not even report normal values for women versus men. This topic will discuss normal reference ranges for laboratory values during pregnancy based upon our review of the literature [1-74].
NORMAL REFERENCE RANGES IN PREGNANCY
Previous investigators have compiled information on normal laboratory reference ranges in pregnancy [30,40,43,75]. Using these references, as well as publications by other researchers in which normal values were determined across pregnancy for a number of analytes, we compiled a table of the most common, and some not so common, laboratory test values across pregnancy (table 1) [2-74].
Laboratory test values are grouped by system and listed for each trimester and for nonpregnant adults. The table shows that some analytes, such as the leukocyte count and alkaline phosphatase levels, continue to rise during normal pregnancy. Similarly, the upper limit of normal for D-dimer nearly doubles from the first to the third trimester. Several hormones and coagulation factors all increase markedly. Unless these normal, pregnancy-related alterations are taken into account when evaluating laboratory values in a pregnant woman, many of the physiologic adaptations of pregnancy can be misinterpreted as pathologic or may mask diagnosis of a disease process.
We consider these data the best available information on normal reference ranges in pregnancy; however, with some limitations. The analysis is subject to the inherent limitations of abridged data, and does not account for potential variations between racial groups, regions of the world, and time of day of sampling. Although we have tried to include comparisons of analytes performed by similar analytic methods, some variation is inevitable. In the majority of instances, reference ranges for analytes are expressed as 5th to 95th percentiles, but some are reported with standard deviations. In addition, pregnancy-specific information is not always available for laboratory tests that have been newly introduced into medical care or have recently gained in popularity. For example, there is sparse information on some tests currently used in cardiac evaluation (atrial natriuretic peptide, B-type natriuretic peptide [BNP], troponin, creatine kinase, and creatine kinase-MB) in pregnancy. Despite these limitations, the table is intended to provide a quick reference for most laboratory values needed to provide care for the pregnant woman.To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- Stagnaro-Green A, Abalovich M, Alexander E, et al. Guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and postpartum. Thyroid 2011; 21:1081.
- Acromite MT, Mantzoros CS, Leach RE, et al. Androgens in preeclampsia. Am J Obstet Gynecol 1999; 180:60.
- Izquierdo Alvarez S, Castañón SG, Ruata ML, et al. Updating of normal levels of copper, zinc and selenium in serum of pregnant women. J Trace Elem Med Biol 2007; 21 Suppl 1:49.
- Ardawi MS, Nasrat HA, BA'Aqueel HS. Calcium-regulating hormones and parathyroid hormone-related peptide in normal human pregnancy and postpartum: a longitudinal study. Eur J Endocrinol 1997; 137:402.
- Karim SA, Khurshid M, Rizvi JH, et al. Platelets and leucocyte counts in pregnancy. J Pak Med Assoc 1992; 42:86.
- Bacq Y, Zarka O, Bréchot JF, et al. Liver function tests in normal pregnancy: a prospective study of 103 pregnant women and 103 matched controls. Hepatology 1996; 23:1030.
- Balloch AJ, Cauchi MN. Reference ranges for haematology parameters in pregnancy derived from patient populations. Clin Lab Haematol 1993; 15:7.
- Beguin Y, Lipscei G, Thoumsin H, Fillet G. Blunted erythropoietin production and decreased erythropoiesis in early pregnancy. Blood 1991; 78:89.
- Belo L, Caslake M, Gaffney D, et al. Changes in LDL size and HDL concentration in normal and preeclamptic pregnancies. Atherosclerosis 2002; 162:425.
- Belo L, Santos-Silva A, Rocha S, et al. Fluctuations in C-reactive protein concentration and neutrophil activation during normal human pregnancy. Eur J Obstet Gynecol Reprod Biol 2005; 123:46.
- Bianco I, Mastropietro F, D'Asero C, et al. Serum levels of erythropoietin and soluble transferrin receptor in the course of pregnancy in non beta thalassemic and beta thalassemic women. Haematologica 2000; 85:902.
- Borghi C, Esposti DD, Immordino V, et al. Relationship of systemic hemodynamics, left ventricular structure and function, and plasma natriuretic peptide concentrations during pregnancy complicated by preeclampsia. Am J Obstet Gynecol 2000; 183:140.
- Hauser, SL, Longo, DL. Harrison's Principles of internal medicine, 15th ed. In: Braunwald, E, Fauci, AS, Kasper, DL, Jameson, JL (Eds), McGraw-Hill, New York 2001.
- Carranza-Lira S, Hernández F, Sánchez M, et al. Prolactin secretion in molar and normal pregnancy. Int J Gynaecol Obstet 1998; 60:137.
- Carter J. Serum bile acids in normal pregnancy. Br J Obstet Gynaecol 1991; 98:540.
- Cerneca F, Ricci G, Simeone R, et al. Coagulation and fibrinolysis changes in normal pregnancy. Increased levels of procoagulants and reduced levels of inhibitors during pregnancy induce a hypercoagulable state, combined with a reactive fibrinolysis. Eur J Obstet Gynecol Reprod Biol 1997; 73:31.
- Choi JW, Pai SH. Tissue plasminogen activator levels change with plasma fibrinogen concentrations during pregnancy. Ann Hematol 2002; 81:611.
- Davison JM, Vallotton MB, Lindheimer MD. Plasma osmolality and urinary concentration and dilution during and after pregnancy: evidence that lateral recumbency inhibits maximal urinary concentrating ability. Br J Obstet Gynaecol 1981; 88:472.
- Desoye G, Schweditsch MO, Pfeiffer KP, et al. Correlation of hormones with lipid and lipoprotein levels during normal pregnancy and postpartum. J Clin Endocrinol Metab 1987; 64:704.
- Dunlop W. Serial changes in renal haemodynamics during normal human pregnancy. Br J Obstet Gynaecol 1981; 88:1.
- Dux S, Yaron A, Carmel A, Rosenfeld JB. Renin, aldosterone, and serum-converting enzyme activity during normal and hypertensive pregnancy. Gynecol Obstet Invest 1984; 17:252.
- Elsheikh A, Creatsas G, Mastorakos G, et al. The renin-aldosterone system during normal and hypertensive pregnancy. Arch Gynecol Obstet 2001; 264:182.
- Ezimokhai M, Davison JM, Philips PR, Dunlop W. Non-postural serial changes in renal function during the third trimester of normal human pregnancy. Br J Obstet Gynaecol 1981; 88:465.
- Fadel HE, Northrop G, Misenhimer HR, Harp RJ. Acid-base determinations in amniotic fluid and blood of normal late pregnancy. Obstet Gynecol 1979; 53:99.
- Faught W, Garner P, Jones G, Ivey B. Changes in protein C and protein S levels in normal pregnancy. Am J Obstet Gynecol 1995; 172:147.
- Francalanci I, Comeglio P, Liotta AA, et al. D-dimer concentrations during normal pregnancy, as measured by ELISA. Thromb Res 1995; 78:399.
- Handwerker SM, Altura BT, Altura BM. Serum ionized magnesium and other electrolytes in the antenatal period of human pregnancy. J Am Coll Nutr 1996; 15:36.
- Higby K, Suiter CR, Phelps JY, et al. Normal values of urinary albumin and total protein excretion during pregnancy. Am J Obstet Gynecol 1994; 171:984.
- Hwang HS, Kwon JY, Kim MA, et al. Maternal serum highly sensitive C-reactive protein in normal pregnancy and pre-eclampsia. Int J Gynaecol Obstet 2007; 98:105.
- Hytten, FE, Lind T. Diagnostic Indices in Pregnancy. Summit, New Jersey, CIBAGEIGY Corporation, 1975.
- Ilhan N, Ilhan N, Simsek M. The changes of trace elements, malondialdehyde levels and superoxide dismutase activities in pregnancy with or without preeclampsia. Clin Biochem 2002; 35:393.
- Jimenez DM, Pocovi M, Ramon-Cajal J, et al. Longitudinal study of plasma lipids and lipoprotein cholesterol in normal pregnancy and puerperium. Gynecol Obstet Invest 1988; 25:158.
- Karsenti D, Bacq Y, Bréchot JF, et al. Serum amylase and lipase activities in normal pregnancy: a prospective case-control study. Am J Gastroenterol 2001; 96:697.
- Kato T, Seki K, Matsui H, Sekiya S. Monomeric calcitonin in pregnant women and in cord blood. Obstet Gynecol 1998; 92:241.
- Kim EH, Lim JH, Kim YH, Park YW. The relationship between aldosterone to renin ratio and RI value of the uterine artery in the preeclamptic patient vs. normal pregnancy. Yonsei Med J 2008; 49:138.
- Kline JA, Williams GW, Hernandez-Nino J. D-dimer concentrations in normal pregnancy: new diagnostic thresholds are needed. Clin Chem 2005; 51:825.
- Koscica KL, Bebbington M, Bernstein PS. Are maternal serum troponin I levels affected by vaginal or cesarean delivery? Am J Perinatol 2004; 21:31.
- Kratz, A, Pesce, MA, Fink, DJ. Appendix: Laboratory values of clinical importance. In: Harrison's Principles of Internal Medicine, 17th ed, Fauci, AS, Braunwald, E, Kasper, DL (Eds), New York, McGraw-Hill, 2008, Appendix 1. p.A-1.
- Larrea F, Méndez I, Parra A, Espinosa de los Monteros A. Serum pattern of different molecular forms of prolactin during normal human pregnancy. Hum Reprod 1993; 8:1617.
- Larsson A, Palm M, Hansson LO, Axelsson O. Reference values for clinical chemistry tests during normal pregnancy. BJOG 2008; 115:874.
- Lefkowitz JB, Clarke SH, Barbour LA. Comparison of protein S functional and antigenic assays in normal pregnancy. Am J Obstet Gynecol 1996; 175:657.
- Leiserowitz GS, Evans AT, Samuels SJ, et al. Creatine kinase and its MB isoenzyme in the third trimester and the peripartum period. J Reprod Med 1992; 37:910.
- Lockitch, G. Handbook of diagnostic biochemistry and hematology in normal pregnancy. Boca Raton (FL): CRC Press; 1993.
- López-Quesada E, Vilaseca MA, Lailla JM. Plasma total homocysteine in uncomplicated pregnancy and in preeclampsia. Eur J Obstet Gynecol Reprod Biol 2003; 108:45.
- Louro MO, Cocho JA, Tutor JC. Assessment of copper status in pregnancy by means of determining the specific oxidase activity of ceruloplasmin. Clin Chim Acta 2001; 312:123.
- Milman N, Bergholt T, Byg KE, et al. Reference intervals for haematological variables during normal pregnancy and postpartum in 434 healthy Danish women. Eur J Haematol 2007; 79:39.
- Milman N, Byg KE, Hvas AM, et al. Erythrocyte folate, plasma folate and plasma homocysteine during normal pregnancy and postpartum: a longitudinal study comprising 404 Danish women. Eur J Haematol 2006; 76:200.
- Milman N, Graudal N, Nielsen OJ, Agger AO. Serum erythropoietin during normal pregnancy: relationship to hemoglobin and iron status markers and impact of iron supplementation in a longitudinal, placebo-controlled study on 118 women. Int J Hematol 1997; 66:159.
- Mimouni F, Tsang RC, Hertzberg VS, et al. Parathyroid hormone and calcitriol changes in normal and insulin-dependent diabetic pregnancies. Obstet Gynecol 1989; 74:49.
- Montelongo A, Lasunción MA, Pallardo LF, Herrera E. Longitudinal study of plasma lipoproteins and hormones during pregnancy in normal and diabetic women. Diabetes 1992; 41:1651.
- Moran P, Baylis PH, Lindheimer MD, Davison JM. Glomerular ultrafiltration in normal and preeclamptic pregnancy. J Am Soc Nephrol 2003; 14:648.
- Morse M. Establishing a normal range for D-dimer levels through pregnancy to aid in the diagnosis of pulmonary embolism and deep vein thrombosis. J Thromb Haemost 2004; 2:1202.
- O'Leary P, Boyne P, Flett P, et al. Longitudinal assessment of changes in reproductive hormones during normal pregnancy. Clin Chem 1991; 37:667.
- Ozerol E, Ozerol I, Gökdeniz R, et al. Effect of smoking on serum concentrations of total homocysteine, folate, vitamin B12, and nitric oxide in pregnancy: a preliminary study. Fetal Diagn Ther 2004; 19:145.
- Parente JV, Franco JG Jr, Greene LJ, et al. Angiotensin-converting enzyme: serum levels during normal pregnancy. Am J Obstet Gynecol 1979; 135:586.
- Piechota W, Staszewski A. Reference ranges of lipids and apolipoproteins in pregnancy. Eur J Obstet Gynecol Reprod Biol 1992; 45:27.
- Pitkin RM, Gebhardt MP. Serum calcium concentrations in human pregnancy. Am J Obstet Gynecol 1977; 127:775.
- Price A, Obel O, Cresswell J, et al. Comparison of thyroid function in pregnant and non-pregnant Asian and western Caucasian women. Clin Chim Acta 2001; 308:91.
- Qvist I, Abdulla M, Jägerstad M, Svensson S. Iron, zinc and folate status during pregnancy and two months after delivery. Acta Obstet Gynecol Scand 1986; 65:15.
- Radder JK, van Roosmalen J. HbA1c in healthy, pregnant women. Neth J Med 2005; 63:256.
- Reiter EO, Braunstein GD, Vargas A, Root AW. Changes in 25-hydroxyvitamin D and 24,25-dihydroxyvitamin D during pregnancy. Am J Obstet Gynecol 1979; 135:227.
- Risberg A, Larsson A, Olsson K, et al. Relationship between urinary albumin and albumin/creatinine ratio during normal pregnancy and pre-eclampsia. Scand J Clin Lab Invest 2004; 64:17.
- Romslo I, Haram K, Sagen N, Augensen K. Iron requirement in normal pregnancy as assessed by serum ferritin, serum transferrin saturation and erythrocyte protoporphyrin determinations. Br J Obstet Gynaecol 1983; 90:101.
- Shakhmatova EI, Osipova NA, Natochin YV. Changes in osmolality and blood serum ion concentrations in pregnancy. Hum Physiol 2000; 26:92.
- Sharma SC, Sabra A, Molloy A, Bonnar J. Comparison of blood levels of histamine and total ascorbic acid in pre-eclampsia with normal pregnancy. Hum Nutr Clin Nutr 1984; 38:3.
- Shivvers SA, Wians FH Jr, Keffer JH, Ramin SM. Maternal cardiac troponin I levels during normal labor and delivery. Am J Obstet Gynecol 1999; 180:122.
- Singh HJ, Mohammad NH, Nila A. Serum calcium and parathormone during normal pregnancy in Malay women. J Matern Fetal Med 1999; 8:95.
- Spiropoulos K, Prodromaki E, Tsapanos V. Effect of body position on PaO2 and PaCO2 during pregnancy. Gynecol Obstet Invest 2004; 58:22.
- Strickland DM, Hauth JC, Widish J, et al. Amylase and isoamylase activities in serum of pregnant women. Obstet Gynecol 1984; 63:389.
- Suri D, Moran J, Hibbard JU, et al. Assessment of adrenal reserve in pregnancy: defining the normal response to the adrenocorticotropin stimulation test. J Clin Endocrinol Metab 2006; 91:3866.
- van Buul EJ, Steegers EA, Jongsma HW, et al. Haematological and biochemical profile of uncomplicated pregnancy in nulliparous women; a longitudinal study. Neth J Med 1995; 46:73.
- van den Broe NR, Letsky EA. Pregnancy and the erythrocyte sedimentation rate. BJOG 2001; 108:1164.
- Walker MC, Smith GN, Perkins SL, et al. Changes in homocysteine levels during normal pregnancy. Am J Obstet Gynecol 1999; 180:660.
- Wickström K, Edelstam G, Löwbeer CH, et al. Reference intervals for plasma levels of fibronectin, von Willebrand factor, free protein S and antithrombin during third-trimester pregnancy. Scand J Clin Lab Invest 2004; 64:31.
- Ramsay M. Appendix of normal values. In: High-risk pregnancy: management options, 3rd ed, James DK, Steer P, Weiner C, Gonik B (Eds), WB Saunders, New York 2005.