Letter to the Editor

Editor, – In addition to the tests mentioned in the article 'Abnormal laboratory results: Biochemical tests in pregnancy' (Aust Prescr 2005;28:98-101), there are several other tests where the changes in the normal ranges during pregnancy are of clinical importance.

  • Serum bicarbonate falls by approximately 4 mmol/L to compensate for the respiratory alkalosis which results from elevated progesterone concentrations stimulating respiratory drive.1
  • Serum vitamin B12falls in 25% of pregnant women such that a value of greater than 100 pmol/L should be regarded as normal for pregnancy. In the absence of folate deficiency serum homocysteine is of value in establishing true B12deficiency in pregnancy.2,3
  • Erythrocyte sedimentation rate rises significantly (often up to 100 mm/hour).4
  • White cell count rises due to neutrophil leucocytosis.5
  • D-dimer becomes elevated in second and third trimesters.6
  • Free protein S concentrations fall significantly.7
  • Creatine kinase (MB subfraction) rises after vaginal delivery.8
  • Serum troponin may be elevated in pre-eclampsia making diagnosis of myocardial ischaemia problematic if mothers develop pulmonary oedema.9
  • Plasma renin activity and serum aldosterone rise masking detection of primary aldosteronism as a cause of pre-gestational hypertension in pregnancy.10

Adam Morton
Senior staff specialist, Endocrinology and Obstetric Medicine
Mater Adult Hospital


Author's comments

Dr H.A. Tran, author of the article, comments:

Dr Morton's comments on other laboratory parameters that change during pregnancy are very much appreciated. The article aimed to highlight biochemical changes in common tests without being overly exhaustive. Generally speaking, pregnancy is a volume retentive, prothrombotic and nutritionally challenged state which results in all the corresponding changes described.

The hypervolaemic state is the result of an activated renin-angiotensin system with markedly elevated aldosterone concentrations and plasma renin activity. The normal physiological control of this system however remains intact, distinguishing it from primary hyperaldosteronism during pregnancy.11

The prothrombotic state is highlighted by the elevated d-dimer concentrations and reduced free protein S concentrations. The latter is the result of elevated protein binding capacity which is typical of pregnancy. Similarly, elevated transcobalamin and haptocorrin concentrations contribute to the reduction in cobalamin concentrations12although preferential fetal transfer during pregnancy also adds to the problem, particularly in vegans. It is probably more cost-effective to replenish B12storage empirically for the duration rather than relying on homocysteine concentrations to diagnose B12deficiency. Erythrocyte sedimentation rate, by way of physiological anaemia during pregnancy, is expected to be elevated but usually not to 100 mm/hour. The mean peak ranges from 50-70 mm/hour depending on the gestational age.13Thus, where it exceeds 100 mm/hour it is important that active inflammation or infection is excluded. Similarly, while white cell count can rise up to 15-16 x 106/mL, the majority often do not exceed the non-pregnant reference range.14



  1. McAuliffe F, Kametas N, Krampl E, Ernsting J, Nicolaides K. Blood gases in pregnancy at sea level and at high altitude. BJOG 2001;108:980-5.
  2. Metz J, McGrath K, Bennett M, Hyland K, Bottiglieri T. Biochemical indices of vitamin B12 nutrition in pregnant patients with subnormal serum vitamin B12 levels. Am J Hematol 1995;48:251-5.
  3. Pardo J, Gindes L, Orvieto R. Cobalamin (vitamin B12) metabolism during pregnancy. Int J Gynaecol Obstet 2004;84:77-8.
  4. Salawu L, Durosinmi MA. Erythrocyte rate and plasma viscosity in health and disease. Niger J Med 2001;10:11-3.
  5. Karim SA, Khurshid M, Rizvi JH, Jafarey SN, Rizwana I. Platelets and leucocyte counts in pregnancy. J Pak Med Assoc 1992;42:86-7.
  6. Kline JA, Williams GW, Hernandez-Nino J. D-dimer concentrations in normal pregnancy: new diagnostic thresholds are needed. Clin Chem 2005;51:825-9.
  7. Wickstrom K, Edelstam G, Lowbeer CH, Hansson LO, Siegbahn A. 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;64:31-40.
  8. Leiserowitz GS, Evans AT, Samuels SJ, Omand K, Kost GJ. Creatine kinase and its MB isoenzyme in the third trimester and the peripartum period. J Reprod Med 1992;37:910-6.
  9. Fleming SM, O'Gorman T, Finn J, Grimes H, Daly K, Morrison JJ. Cardiac troponin I in pre-eclampsia and gestational hypertension. BJOG 2000;107:1417-20.
  10. 10. Bentley-Lewis R, Graves SW, Seely EW. The renin-aldosterone response to stimulation and suppression during normal pregnancy. Hypertens Pregnancy 2005;24:1-16.
  11. Bentley-Lewis R, Graves SW, Seely EW. The renin-aldosterone response to stimulation and suppression during normal pregnancy. Hypertens Pregnancy 2005;24:1-16.
  12. Koebnick C, Heins UA, Dagnelie PC, Wickramasinghe SN, Ratnayaka ID, Hothorn T, et al. Longitudinal concentrations of vitamin B(12) and vitamin B(12)-binding proteins during uncomplicated pregnancy. Clin Chem 2002;48:928-33.
  13. van den Broe NR, Letsky EA. Pregnancy and the erythrocyte sedimentation rate. BJOG 2001;108:1164-7.
  14. Hiss RG. Evaluation of the anaemic patient. In: Laros Jr RK, editor. Blood disorders in pregnancy. Philadelphia: Lea & Febiger; 1986. p. 9.

The Editorial Executive Committee welcomes letters, which should be less than 250 words. Before a decision to publish is made, letters which refer to a published article may be sent to the author for a response. Any letter may be sent to an expert for comment. When letters are published, they are usually accompanied in the same issue by their responses or comments. The Committee screens out discourteous, inaccurate or libellous statements. The letters are sub-edited before publication. Authors are required to declare any conflicts of interest. The Committee's decision on publication is final.

Adam Morton

Senior staff specialist, Endocrinology and Obstetric Medicine, Mater Adult Hospital, Brisbane

Huy A. Tran

Head and Associate Professor, Department of Clinical Chemistry, Hunter Area Pathology Service, John Hunter Hospital, Newcastle University, Newcastle, New South Wales