Management and Prevention

of Preeclampsia
Sarma Nursani Lumbanraja

Maternal Fetal Medicine Division - Faculty of Medicine

Universitas Sumatera Utara
 Hypertension in pregnancy
• Chronic hypertension
• Gestational hypertension
• Preeclampsia
• Chronic hypertension superimposed with preeclampsia

Brown MA, Lindheimer MD, de Swiet M, et al. The classification and diagnosis of the hypertensive disorders of pregnancy: statement from the
international society for the study of hypertension in pregnancy (ISSHP). Hypertens Pregnancy 2001; 20(1):ix–xiv.
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(5):1122.
 PREECLAMPSIA
Preeclampsia is defined as hypertension in association with either
• Proteinuria (>300 mg in 24 hours)
• Thrombocytopenia (<100,000/ml)
• Impaired liver function
• Renal insufficiency (>1.1 mg/dl)
• Pulmonary edema
• New-onset cerebral or visual disturbances.
Brown MA, Lindheimer MD, de Swiet M, et al. The classification and diagnosis of the hypertensive disorders of pregnancy: statement from the
international society for the study of hypertension in pregnancy (ISSHP). Hypertens Pregnancy 2001; 20(1):ix–xiv.
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(5):1122.
Townsend R, O’Brien P, Khalil A. Current best practice in the management of hypertensive disorders in pregnancy.
Integrated Blood Pressure Control 2016:9 79–94
 PREECLAMPSIA
“Preeclampsia Affects Not Only the Mother but Also the Offspring”
• Therefore, focus of clinical management of preeclampsia are :
• Prevention of maternal morbidity
• Maternal seizure prevention in severe preeclampsia
• Limiting injury to the fetus.

Guillemette L, Lacroix M, Allard C, Patenaude J, Battista M, Doyon M et al. Preeclampsia is associated with an increased proinflammatory profile in newborns.
J Reprod Immunol. 2015;112: 111-4. 68.
Nomura Y, John R, Janssen A, Davey C, Finik J, Buthmann J et al. Neurodevelopmental consequences in offspring of mothers with preeclampsia during
pregnancy: underlying biological mechanism via imprinting genes. Arch Gyneccol Obstet. 2017;295(6):1319-29.
 PREECLAMPSIA
• If treatment fails to correct severe maternal hypertension or if there is
evidence of non-reassuring fetal status, delivery is warranted.

Guillemette L, Lacroix M, Allard C, Patenaude J, Battista M, Doyon M et al. Preeclampsia is associated with an increased proinflammatory profile in newborns.
J Reprod Immunol. 2015;112: 111-4. 68.
Nomura Y, John R, Janssen A, Davey C, Finik J, Buthmann J et al. Neurodevelopmental consequences in offspring of mothers with preeclampsia during
pregnancy: underlying biological mechanism via imprinting genes. Arch Gyneccol Obstet. 2017;295(6):1319-29.
Timing of Delivery
• Management of preeclamptic patients is focused on balancing the risks to both mother and
fetus of continuing the pregnancy with the benefits to the fetus of delivering it as fully
developed as possible.

• Current recommendations are to deliver women who present with severe preeclampsia at
or beyond 37 0/7 weeks of gestation. Additionally, women between 34 0/7 and 37 0/7
weeks with progressive labor, rupture of membranes, intrauterine growth retardation,
oligohydramnios, or a biophysical profile of 6/10 or less should also be delivered. Finally,
delivery should occur immediately in suspected cases of fetal abruption.
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(5):1122.
Magnesium Sulfate
• Prophylaxis against maternal seizures (eclampsia) : Magnesium sulfate IV or
IM
• Magnesium sulfate  favorable effect of lowering maternal blood pressure
• Superior to other anticonvulsants in the prevention of eclamptic seizures and
is considered first-line therapy.
• However, when magnesium sulfate is either contraindicated or unavailable,
traditional anticonvulsants may be used.

Prins J, Boelens H, Heimweg J, Van der Heide S, Dubois A, Van Oosterhout A, et al. Preeclampsia is associated with
lower percentages of regulatory T cells in maternal blood. Hypertension in Pregnancy. 2009;28:300–11.
 SIDE EFFECTS OF MAGNESIUM SULFATE

Turner JA. Diagnosis and Management of Preeclampsia : an update. International Journal of Women’s Health. 2010 :
2.327-337
Antihypertensive
• Blood pressure targets differ slightly for postpartum patients compared with
undelivered mothers.
Antepartum:
• Reduce blood pressure to achieve ranges consistently below the severe range
(<160/110 mm Hg) as so-called high-normal levels.
• Therapy should be given within 1 hour of persistent severe-range blood
pressures (ideally within 15 minutes).
• Blood pressure should be reduced to approximately 140 to 150 over 90 to 100
mm Hg and not any lower to avoid hypoperfusion of the fetus and maternal
organs.
Elfarra J, Bean C, Martin JN. Management of Hypertensive Crisis for the Obstetrician/Gynecologist. Obstet Gynecol Clin
N Am.Elsevier.2016
Antihypertensive
Postpartum:
• Therapy should be given within 1 hour of persistent severe-range blood
pressures.
• Reduce blood pressure to achieve levels consistently less than 150/90 mm Hg.
• Blood pressure should be monitored closely for the first 72 hours postpartum.
• Outpatient surveillance should be considered for those discharged before 72
hours (eg, home nursing visit).
• Reevaluate the patient within 7 to 10 days of discharge.
• Avoid nonsteroidal antiinflammatory drugs in the hypertensive postpartum
patient.
Elfarra J, Bean C, Martin JN. Management of Hypertensive Crisis for the Obstetrician/Gynecologist. Obstet Gynecol Clin
N Am.Elsevier.2016
American College of Obstetrics and Gynecology Committee opinion no. 623:emergent therapy for acute-onset, severe hypertension during
pregnancy and the postpartum period. Obstet Gynecol 2015;125(2):521–5.
Balogun OAA, Sibai BM. Counseling, Management, and Outcome in Women With Severe Preeclampsia at 23 to 28
Weeks’ Gestation. Clinical Obstetrics And Gynecology. Volume 60, Number. 2017
Townsend R, O’Brien P, Khalil A. Current best practice in the management of hypertensive disorders in pregnancy.
Integrated Blood Pressure Control 2016:9 79–94
Townsend R, O’Brien P, Khalil A. Current best practice in the management of hypertensive disorders in pregnancy.
Integrated Blood Pressure Control 2016:9 79–94
Anesthesia

• Current guidelines support placing spinal or epidural catheter early for

preeclamptic patients to reduce the need for general anesthesia in an
emergency requiring urgent delivery.
• Unless contraindicated, the preferred method of analgesia for both laboring
patients and cesarean section is neuraxial anesthesia.
• General anesthesia is used when the preeclamptic patients present with
eclampsia, pulmonary edema, depressed levels of consciousness, or signs or
symptoms of cerebral edema.

Dhariwal NK, Lynde GC. Update in The Management of Patients With Preeclampsia. Anesthesiology Clin.2016
 Postpartum Management
• After delivery, all women with SPE should be given magnesium sulfate
for 24 hours from when diagnosis is made.
• Antihypertensive therapy : when blood pressure is persistently higher
than 150 mm Hg systolic or 100 mm Hg diastolic on at least 2 occasions
that are 4 to 6 hours apart.
• In women with SPE, blood pressure usually decreases within 48 hours
after delivery; however, there can be an increase again 3 to 6 days
postpartum
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(5):1122.
Sibai BM. Etiology and management of postpartum hypertension-preeclampsia. Am J Obstet Gynecol. 2012;206:470–475.
 Counseling for Future Pregnancies
• In women with SPE, the rate of preeclampsia in subsequent pregnancy
is approximately 50%, and the rate of preterm SPE is around 10%.
• Ideally counseling of patients with a history of SPE should begin
preconceptually; however, because late entry into prenatal care may
occur, these recommendations can be given at the 6 week postpartum
visit.

Balogun OAA, Sibai BM. Counseling, Management, and Outcome in Women With Severe Preeclampsia at 23 to 28
Weeks’ Gestation. Clinical Obstetrics And Gynecology. Volume 60, Number. 2017
Counseling for Future Pregnancies
• Recommendations should include risk modification strategies to
reduce SPE recurrence.
• Preeclampsia is correlated with the severity of maternal hypertension,
glycemic control, and obesity
• Therefore, tight control of blood pressures along with lifestyle
modifications should be attempted before conception.

Balogun OAA, Sibai BM. Counseling, Management, and Outcome in Women With Severe Preeclampsia at 23 to 28
Weeks’ Gestation. Clinical Obstetrics And Gynecology. Volume 60, Number. 2017
Prevention of Preeclampsia

• Currently, delivery is the only cure for preeclampsia; therefore,

effective prevention and treatment options for this condition are
sorely needed.
INTERVENTION FOR PREVENTION OF PREECLAMPSIA

Bramham K, Hladunewich MA, Jim B, Maynard SE. Pregnancy and kidney disease. NephSAP. 2016;15:1-104.
 Prevention of Preeclampsia
• A systematic review and meta analysis from 45 randomized controlled
trials were performed in 2015, which included a total of 20,909
pregnant women randomized to between 50-150 mg of aspirin daily.
• The results of this meta-analysis suggest that in high-risk women the
effect of aspirin for the prevention of PE, severe PE, and FGR is dose-
dependent and optimal when initiated less than 16 weeks of
gestation.

Roberge S et al. The role of aspirin dose on the prevention of preeclampsia and fetal growth restriction:
systematic review and meta-analysis. Am J Obstet Gynecol 2017.
Prevention of Preeclampsia
• Other studied modality for preeclampsia prevention is vitamin D
serum level.
• It is not clear how vitamin d may influence preeclampsia risk
• Vitamin D likely plays a role in placental development, possibly by
regulating genes associated with placental invasion and implantation
as well as influencing immune reactions and inflammation at the
maternal-fetal interface

Grotegut CA.Prevention of Preeclampsia. J Clin Invest. 2016;126(12):4396-4398

 Novel Therapy for the
Treatment of Early-Onset Preeclampsia
Preclinically Assessed Therapeutics
• ETA Receptor Blockade
• Mesenchymal Stem Cells (MSCs)
• Regulatory T Cells
• Anti-inflammatory And Immunosuppressant Agents (Celecoxib,
Sulfasalazine, Azathioprine, Mycophenolate Mofetil, Cyclosporine A)
• Hydrogen Sulfide (H2S)
• Angiogenic Molecules Replacement
• Antiangiogenic Molecules Inhibitors
• a-1 Microglobulin (A1M)
Ornaghi S, Paidas MJ. Novel Therapy For The Treatment Of Early-onset Preeclampsia. Clinical Obstetrics And Gynecology.
Volume 60, Number 1, 169–182
 Novel Therapy for the
Treatment of Early-Onset Preeclampsia
Clinically Assessed Therapeutics
• Antithrombin (AT)
• Lipid-regulating Agents (Statin, apheresis)
• Serelaxin Or RLX030 (RECOMBINANT HUMAN RELAXIN-2)
• Sildenafil
• NO Donors And Precursors
• Antidigoxin Antibody (Digibind)
• Recombinant Human-Activated Protein C (APC)
• Melatonin
• Antiangiogenic Molecules Inhibitors

Ornaghi S, Paidas MJ. Novel Therapy For The Treatment Of Early-onset Preeclampsia. Clinical Obstetrics And Gynecology.
Volume 60, Number 1, 169–182
 “Currently, no therapies are available to slow or reverse
the disease.“

Ornaghi S, Paidas MJ. Novel Therapy For The Treatment Of Early-onset Preeclampsia. Clinical Obstetrics And Gynecology.
Volume 60, Number 1, 169–182
THANK YOU