Society of Obstetric Medicine of Australia and New Zealand: tests, treatments and procedures clinicians and consumers should question
While older retrospective studies suggested that inherited thrombophilia is associated with adverse pregnancy outcomes such as stillbirth, recurrent miscarriage and placental abruption, more recent and more rigorous studies have either failed to find an association or have found only a weak association. Moreover, the association is a moot point as there is now good quality evidence from randomised controlled trials that low-molecular-weight heparin does not significantly reduce the rate of placental mediated complications.
- Clark P, Walker ID, Langhorne P, et al. SPIN: the Scottish Pregnancy Intervention Study: a multicentre randomised controlled trial of low molecular weight heparin and low dose aspirin in women with recurrent miscarriage. Blood 2010; 115(21):4162-7.
- Rodger MA, Walker MC, Smith GN, et al. Is thrombophilia associated with placenta-mediated pregnancy complications? A prospective cohort study. J of Thrombosis & Haemostasis 2014; 12:469-78.
- Rodger MA, Hague WM, Kingdom J, et al. Antepartum dalteparin versus no antepartum dalteparin for the prevention of pregnancy complications in pregnant women with thrombophilia (TIPPS): a multinational open-label randomised trial. Lancet 2014; 384:1673-83.
- Said JM, Higgins JR, Moses EK, et al. Inherited thrombophilias and adverse pregnancy outcomes: a case-control study in an Australian population. Acta Obstet Gynecol Scand 2012; 91(2):250-5.
- Silver RM, Saade GR, Thorsten V, et al. Factor V Leiden, prothrombin G20210A, and methylene tetrahydrofolate reductase mutations and stillbirth: the Stillbirth Collaborative Research Network. Am J Obstet Gynecol 2016; 215:468.e1-17.
Measuring proteinuria is useful as a diagnostic but not as a prognostic criterion for pre-eclampsia. This is because the level of proteinuria does not correlate with the severity of maternal complications in women with pre-eclampsia, nor are these levels useful in determining the timing of delivery. Thus, repeat testing for proteinuria in managing established pre-eclampsia is not recommended, particularly given the availability of superior prognostic models.
- Lowe SA, Bowyer L, Lust K, et al. The SOMANZ guidelines for the management of hypertensive disorders of pregnancy 2014. ANZJOG 2015; 55:11-6.
- Payne B, Magee LA, Côté AM, et al. PIERS proteinuria: relationship with adverse maternal and perinatal outcome. J Obstet Gynaecol Can 2011; 33(6):588-97.
- Thangaratinam S, Coomarasamy A, O’Mahony F, et al. Estimation of proteinuria as a predictor of complications of pre-eclampsia: a systematic review. BMC Med 2009; 7:10.
- von Dadelszen P, Payne B, Li J, et al. Prediction of adverse maternal outcomes in pre-eclampsia: development and validations of the fullPIERS model. Lancet 2011; 377:219-27.
Patients with the thermolabile variant of the methylenetetrahydrofolate reductase (MTHFR) polymorphism are at higher risk of hyperhomocysteinaemia which has been associated with venous thrombosis. However, these associations appear to hold only in countries lacking grain products nutritionally fortified as a public health measure. Moreover, homozygous variants are found in up to 15 per cent of some populations, so that detection of this variant would lead to many women undergoing complex counselling unnecessarily and may also be a cause of distress. Polymorphism is not more prevalent in women with pregnancy-associated venous thromboembolism and testing for this polymorphism is not recommended as part of a routine evaluation for thrombophilia in pregnancy.
- Den Heijer M, Lewington S, Clarke R. Homocysteine, MTHFR and risk of venous thrombosis: a meta-analysis of published epidemiological studies. J Thromb Haemost 2005; 3:292-9.
- Eldibany MM, Caprini JA. Hyperhomocysteinemia and thrombosis: an overview. Arch Pathol Lab Med 2007; 131:872-84.
- Holmes MV, Newcombe P, Hubacek JA, et al. Effect modification by population dietary folate on the association between MTHFR genotype, homocysteine, and stroke risk: a meta-analysis of genetic studies and randomised trials. Lancet 2011; 378:584-594.
- McLintock C, Brighton T, Chunilal S, et al. Recommendations for the prevention of pregnancy-associated venous thromboembolism. ANZJOG 2012; 52:3-13.
Measuring the erythrocyte sedimentation rate (ESR) is a non-specific test to identify inflammation. An elevated result indicates inflammation but does not indicate where it is in the body or the cause. The normal range outside of pregnancy in women aged 18–50 is <20mm/h. One study found that levels varied 4–70mm/h and another found a range from 4-112mm/h, with levels being affected by gestational age and haemoglobin concentration. This is likely to reflect normal changes in pregnancy, meaning that testing for an elevated ESR does not sufficiently differentiate between healthy pregnant women and those who may be suffering from inflammatory diseases.
- Abbassi-Ghanavati M, Greer LG, Cunningham FG. Pregnancy and laboratory studies: A reference table for clinicians. Obstet Gynecol 2009; 114(6):1326–31.
- van den Broe NR, Letsky EA. Pregnancy and the erythrocyte sedimentation rate. BJOG 2001; 108(11):1164-7.
As evidence and clinical practice advances, Evolve recommendations will reflect these changes following a review. The latest SOMANZ recommendation developments are outlined below.
Removal of recommendation (2019)
The previous iteration of the SOMANZ ‘Top-Five’ recommendations included:
Do not perform a D-Dimer test for the exclusion of venous thromboembolism during any trimester of pregnancy.
Recent studies have shown that using a D-Dimer in combination with a clinical algorithm can increase the reliability of D-Dimer testing in ruling out DVT and PE in pregnancy.
Furthermore, the alternative to D-Dimer tests for these purposes is the use of imaging tests, which have their own set of risks from radiation exposure. Where previous evidence which suggested D-Dimer testing was highly unreliable would have tipped the scales towards discouraging D-Dimer testing, the new evidence suggests the results of D-Dimer testing can be made more reliable. Thus, it is no longer apparent there would be strong benefits from discouraging the use of D-Dimer testing in these settings if the alternative is imaging.
At a 7 August 2019 meeting of the SOMANZ Council it was agreed this recommendation be removed. The RACP Evolve team and the NPS MedicineWise Choosing Wisely Australia Clinical Lead also undertook a review.
Due to this change in evidence, and physician support, this recommendation was officially removed in August 2019.
Supporting evidence for the removal of this recommendation
- Langlois E, Cusson-Dufour C, Moumneh T, et al. Could the YEARS algorithm be used to exclude pulmonary embolism during pregnancy? Data from the CT-PE-pregnancy study. J Thromb Haemost. 2019;17(8):1329-1334
- van der Pol LM, Tromeur C, Bistervels IM, et al. Pregnancy-Adapted YEARS Algorithm for Diagnosis of Suspected Pulmonary Embolism. N Engl J Med 2019; 380:1139-1149.*
Original Recommendation: Do not perform a D-Dimer test for the exclusion of venous thromboembolism during any trimester of pregnancy
As D-Dimer levels are raised during pregnancy, they do not have a high positive predictive value for venous thromboembolism (VTE) in pregnancy (i.e. they are unreliable for ruling in VTE in pregnancy). However, nor are they a reliable rule-out test for VTE. One study estimated the sensitivity of the D-Dimer test at 73 per cent, meaning that 27 per cent of patients with a negative D-Dimer had VTE. There have also been case reports of pregnant women with pulmonary embolism presenting with a negative D-Dimer. Therefore, there is no value in performing a D-Dimer test for the exclusion of venous thromboembolism at any trimester in pregnancy.
- Damodaram M, Kaladindi M, Luckit J, et al. D-dimers as a screening test for venous thromboembolism in pregnancy: is it of any use? Journal of Obstetrics and Gynaecology 2009; 29(2):101-32.
- McLintock C, Brighton T, Chunilal S, et al. Recommendations for the diagnosis and treatment of deep venous thrombosis and pulmonary embolism in pregnancy and the postpartum period. Aust N Z J Obstet Gynaecol 2012; 52(1):14-22.
- To MS, Hunt BJ, Nelson-Piercy C. A negative D-Dimer does not exclude venous thromboembolism in pregnancy. Journal of Obstetrics and Gynaecology 2008; 28(2):222-40.