Dr Fergus McCarthy takes a monthly look at articles just published in the area of hypertension & pre-eclampsia.

 

The prediction of what women and babies will have adverse outcomes remains one of the huge challenges for clinicians. Conveying this information accurately to women is equally as challenging and difficult.

Balogun et al explore the counseling, management, and outcome in women with severe pre-eclampsia at 23 to 28 weeks’ gestation. They reviewed the scientific literature and presented their recommendations on the management of severe pre-eclampsia under 28 week’s gestation.1 Severe pre-eclampsia was classified as having hypertension with or without proteinuria, in the presence of thrombocytopenia (platelet count <100,000 mL), impaired liver function, (elevated blood levels of liver transaminases to twice the upper limit of normal for local laboratories), new development of renal insufficiency (elevated serum creatinine >1.1 mg/dL), pulmonary oedema or new-onset cerebral or visual disturbances.

The literature review included observational studies totaling 305 women with a gestational age between 18 and 27+6 weeks’ gestation. Some interesting findings are reported. Most studies on expectant management report 7 to 10 days of prolongation of pregnancy prior to requiring delivery. Admission before 25 weeks’ gestation with co-existing severe fetal growth restriction (estimated fetal weight <5%) had 100% fetal mortality in some studies. As a result, some studies recommended that immediate delivery, rather than expectant management, should be considered when severe pre-eclampsia is diagnosed under 23 or 24 weeks gestation. Overall, the authors conclude that expectant management of severe pre-eclampsia at <28 weeks is appropriate in selected cases.

Previously we had discussed the adverse long-term cardiovascular morbidity observed in women with pre-eclampsia. What causes this increased risk remains unclear. Mohseni et al examined the association between the concentric left ventricle remodeling that occurs in pre-eclampsia and its association with heart failure later in life by evaluating microRNAs.2 They performed a literature review by firstly extracting data on miRNA expression in relation to cardiac remodeling. Next, data was extracted on miRNAs in relation to pregnancy complicated by pre-eclampsia. Both were compared in order to extract the overlapping miRNA’s between pre-eclampsia and concentric remodeling.

Nine miRNAs overlapped between concentric remodeling and pregnancy complicated by pre-eclampsia; miR-1, miR-18, miR-21, miR-29b, miR-30, miR-125b, miR-181b, miR-195 and miR-499-5p. Five miRNA’s were found to be up-regulated in both PE pregnancy and cardiac remodeling (miR-18, miR-21, miR-125b, miR-195 and miR-499-5p) and two miRNA were downregulated in both (miR-1 and miR-30). Two other miRNAs showed an up-regulation during pre-eclampsia while showing a downregulation in cardiac remodeling (miR-29b and miR-181b).

This study suggests an innovative approach for identifying relevant biomarkers for pregnancy complicated by pre-eclampsia and subsequent cardiovascular disease. This may suggest possible means by which we could stratify those women at high risk of cardiovascular disease following complicated pregnancy.

The search for biomarkers linking both pre-eclampsia and cardiovascular dysfunction was further explored in work by Alma et al who conducted a systematic review examining possible biomarkers which may represent common pathogenic pathways between heart failure with preserved ejection fraction (HFpEF) and pre-eclampsia.3

Two systematic searches were conducted. The first yielded 3014 studies on biomarkers discriminating women with HFpEF from female controls, of which 13 studies on 11 biochemical markers were included. The second search was for studies discriminating women with pre-eclampsia from women with non-hypertensive pregnancies with at least one of the biomarkers found in Search I. This yielded 1869 studies, of which 51 studies on seven biomarkers were included in meta-analyses and 79 studies on 12 biomarkers in the systematic review.

Eleven biological markers differentiated women with diastolic dysfunction from controls, of which the following 10 markers differentiated women with pre-eclampsia from controls as well: C-reactive protein, HDL, insulin, fatty acid-binding protein 4, brain natriuretic peptide, N terminal pro brain natriuretic peptide, adrenomedullin, mid-region pro adrenomedullin, cardiac troponin I, and cancer antigen 125. These biomarkers represent markers of inflammatory states, disturbances in myocardial function/structure, and unfavourable lipid metabolism.

Finally, it is clear the overlap that often co-exists between intrauterine growth restriction and pre-eclampsia. It is also imperative that the impact of interventions in the developed world are examined critically in developing countries as effects in low resource settings may be very different.

Hoffman et al present their study protocol in which they describe a prospective randomized, placebo-controlled, double-blinded multi-national clinical trial to be conducted in seven low and middle-income countries.4 Nulliparous women between the ages of 14 and 40, with a singleton pregnancy recruited, will be administered daily administration of low-dose (81 mg) aspirin, initiated between 6 0/7 weeks and 13 6/7 weeks GA and continued to 36 0/7 weeks GA, compared to an identical appearing placebo.

The primary outcome: will be the incidence of PTB (<37 0/7 weeks GA). Secondary outcomes will include incidence of pre-eclampsia/eclampsia, small for gestational age and perinatal mortality.

 

References

  1. Balogun OA, Sibai BM. Counseling, Management, and Outcome in Women With Severe Preeclampsia at 23 to 28 Weeks’ Gestation. Clinical obstetrics and gynecology. Mar 2017;60(1):183-189.
  2. Mohseni Z, Spaanderman MEA, Oben J, Calore M, Derksen E, Al-Nasiry S, de Windt L, Ghossein-Doha C. Cardiac remodelling and preeclampsia: an overview of overlapping circulating miRNAs. Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology. May 03 2017.
  3. Alma LJ, Bokslag A, Maas A, Franx A, Paulus WJ, de Groot CJM. Shared biomarkers between female diastolic heart failure and pre-eclampsia: a systematic review and meta-analysis. ESC heart failure. May 2017;4(2):88-98.
  4. Hoffman MK, Goudar SS, Kodkany BS, Goco N, Koso-Thomas M, Miodovnik M, McClure EM, Wallace DD, Hemingway-Foday JJ, Tshefu A, et al. A description of the methods of the aspirin supplementation for pregnancy indicated risk reduction in nulliparas (ASPIRIN) study. BMC pregnancy and childbirth. May 03 2017;17(1):135.