Defining a Strategy for Laboratory Evaluation with Expectant Management of Preeclampsia

Abstract

Objective The objective of this study was to compare the frequency and timing of laboratory abnormalities and evaluate optimal laboratory testing strategies in women with preeclampsia (PE) undergoing expectant management.

Study Design Retrospective cohort study of women with inpatient expectant management of PE at ≥23 weeks at a tertiary center from 2015 to 2018 was conducted. Women ineligible for expectant management or with less than two laboratory sets (platelets, aspartate aminotransferase, and serum creatinine) before the decision to deliver were excluded. Women were categorized as per the American College of Obstetricians and Gynecologists' definitions by initial diagnosis: PE without severe features, superimposed preeclampsia (SiPE) without severe features, and their forms with severe features. The frequency and timing of laboratory abnormalities were compared across the four PE categories. Kaplan–Meier curves modeled time to a laboratory abnormality (event) with censoring for delivery and were compared using log-rank tests. Logistic regression analysis modeled the development of a laboratory abnormality as a function of testing time intervals (days) for each PE type. Receiver operating characteristic curves and areas under the curve (AUC) were calculated; optimal cut points were determined using the Liu method.

Results Among 636 women who met inclusion criteria, laboratory abnormalities were uncommon (6.3%). The median time to a laboratory abnormality among all women was ≤10 days, time being shortest in women with PE with severe features. Time to laboratory abnormality development did not differ significantly between the four PE groups (p = 0.36). Laboratory assessment intervals were most predictive for PE and SiPE with severe features (AUC = 0.87, AUC = 0.72). Optimal cutoffs were every 4 days for PE without severe features, 2 days for PE with severe features, 8 days for SiPE without severe features, and 3 days for SiPE with severe features.

Conclusion Most laboratory abnormalities in PE occur earlier and more frequently in those with severe features. Individual phenotypes should undergo serial evaluation based on this risk stratification.

Key Points

• Most laboratory abnormalities occur within 10 days of diagnosis.

• Laboratory abnormalities occur more often with severe features.

• Laboratory testing should occur according to disease severity.

Keywords

laboratory abnormality - optimal testing - severe features - preeclampsia

Note

Paper Presentation: This data was presented in two posters, nos.: 978 and 1136, at the Society for Maternal Fetal Medicine Annual Meeting in Grapevine, TX, February 2020.

Publication History

Received: 24 October 2020

Accepted: 04 October 2021

Article published online:
16 November 2021

• References

• 1 Cunningham FG, Lindheimer MD. Hypertension in pregnancy. N Engl J Med 1992; 326 (14) 927-932
• 2 Roberts JM, Cooper DW. Pathogenesis and genetics of pre-eclampsia. Lancet 2001; 357 (9249): 53-56
• 3 Ananth CV, Keyes KM, Wapner RJ. Pre-eclampsia rates in the United States, 1980-2010: age-period-cohort analysis. BMJ 2013; 347: f6564
• 4 Bodnar LM, Ness RB, Markovic N, Roberts JM. The risk of preeclampsia rises with increasing prepregnancy body mass index. Ann Epidemiol 2005; 15 (07) 475-482
• 5 Flegal KM, Carroll MD, Kit BK, Ogden CL. Prevalence of obesity and trends in the distribution of body mass index among US adults, 1999-2010. JAMA 2012; 307 (05) 491-497
• 6 Wallis AB, Saftlas AF, Hsia J, Atrash HK. Secular trends in the rates of preeclampsia, eclampsia, and gestational hypertension, United States, 1987-2004. Am J Hypertens 2008; 21 (05) 521-526
• 7 Creanga AA, Syverson C, Seed K, Callaghan WM. Pregnancy-related mortality in the United States, 2011-2013. Obstet Gynecol 2017; 130 (02) 366-373
• 8 Sibai BM, Barton JR. Expectant management of severe preeclampsia remote from term: patient selection, treatment, and delivery indications. Am J Obstet Gynecol 2007; 196 (06) 514.e1-514.e9
• 9 Zhang J, Meikle S, Trumble A. Severe maternal morbidity associated with hypertensive disorders in pregnancy in the United States. Hypertens Pregnancy 2003; 22 (02) 203-212
• 10 McDonald SD, Malinowski A, Zhou Q, Yusuf S, Devereaux PJ. Cardiovascular sequelae of preeclampsia/eclampsia: a systematic review and meta-analyses. Am Heart J 2008; 156 (05) 918-930
• 11 Williams D. Long-term complications of preeclampsia. Semin Nephrol 2011; 31 (01) 111-122
• 12 Buchbinder A, Sibai BM, Caritis S. et al; National Institute of Child Health and Human Development Network of Maternal-Fetal Medicine Units. Adverse perinatal outcomes are significantly higher in severe gestational hypertension than in mild preeclampsia. Am J Obstet Gynecol 2002; 186 (01) 66-71
• 13 American College of Obstetricians and Gynecologists, Task Force on Hypertension in Pregnancy. Hypertension in pregnancy. Report of the American College of Obstetricians and Gynecologists' task force on hypertension in pregnancy. Obstet Gynecol 2013; 122 (05) 1122-1131
• 14 Gestational Hypertension and Preeclampsia. Gestational hypertension and preeclampsia: ACOG Practice Bulletin Summary, Number 222. Obstet Gynecol 2020; 135 (06) 1492-1495
• 15 Cantu J, Clifton RG, Roberts JM. et al; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Maternal-Fetal Medicine Units (MFMU) Network. Laboratory abnormalities in pregnancy-associated hypertension: frequency and association with pregnancy outcomes. Obstet Gynecol 2014; 124 (05) 933-940
• 16 Li X, Zhang W, Lin J. et al. Risk factors for adverse maternal and perinatal outcomes in women with preeclampsia: analysis of 1396 cases. J Clin Hypertens (Greenwich) 2018; 20 (06) 1049-1057
• 17 Martin Jr JN, May WL, Magann EF, Terrone DA, Rinehart BK, Blake PG. Early risk assessment of severe preeclampsia: admission battery of symptoms and laboratory tests to predict likelihood of subsequent significant maternal morbidity. Am J Obstet Gynecol 1999; 180 (6 Pt 1): 1407-1414
• 18 Shih T, Peneva D, Xu X. et al. The rising burden of preeclampsia in the United States impacts both maternal and child health. Am J Perinatol 2016; 33 (04) 329-338
• 19 Stevens W, Shih T, Incerti D. et al. Short-term costs of preeclampsia to the United States health care system. Am J Obstet Gynecol 2017; 217 (03) 237-248.e16 , e216
• 20 Liu X. Classification accuracy and cut point selection. Stat Med 2012; 31 (23) 2676-2686
• 21 Mol BWJ, Roberts CT, Thangaratinam S, Magee LA, de Groot CJM, Hofmeyr GJ. Pre-eclampsia. Lancet 2016; 387 (10022): 999-1011
• 22 Possomato-Vieira JS, Khalil RA. Mechanisms of endothelial dysfunction in hypertensive pregnancy and preeclampsia. Adv Pharmacol 2016; 77: 361-431
• 23 Rana S, Karumanchi SA, Lindheimer MD. Angiogenic factors in diagnosis, management, and research in preeclampsia. Hypertension 2014; 63 (02) 198-202