Biomarkers in Management of Post Partum Preeclampsia

The research procedures, including patient enrollment, will occur while admitted to the Labor and Delivery Unit at University of Kentucky Chandler Hospital prior to birth, and no additional visits for the purpose of this research are anticipated. The experimental group will include pregnant participants with preeclampsia with severe features who are randomized to 12 hours of magnesium post-partum. The control group will consist of participants with preeclampsia with severe features randomized to 24 hours of magnesium administration post-partum.

After their initial enrollment, care will not be impacted leading up to the delivery of the neonate. Following delivery, the magnesium sulfate administration will remain a continuous infusion at 2 grams per hour (diluted in lactated ringers for total infusion volume of 50mL per hour) as is standard practice. Care for both groups will remain as standard for nursing monitoring including exam and vital signs at least hourly while on magnesium sulfate continuous infusion.

Both groups at completion of magnesium sulfate, either 12 hours after delivery for the intervention group or 24 hours after delivery for control group, will continue with standard monitoring procedures per institutional protocol.

Both groups will have blood (serum) analysis collected at time of delivery, 12 hours later, then at 18 hours following delivery, and 24 hours. After 24 hours of collection, the lab evaluation will be spaced to daily until discharge. While laboratory evaluation, being collected and analyzed, every 6 hours is a standard practice for many clinical circumstances while admitted for pre-eclampsia with severe features, there is the potential to increased cost if not felt to be clinically indicated post-partum. This cost would not be passed along to patients and would instead be covered by funding acquired for this study. Additionally, some of the serum analytes collected, such as soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) are not part of routine analysis, and costs will be covered by research funding rather than billed to patients.

Analysis will consist of typical preeclampsia markers such as liver transaminases, serum creatinine, platelet counts. Additional analytes will include sFlt-1, PlGF, intracellular adhesion molecule (ICAM), vascular cell adhesion molecule (VCAM), B-type natriuretic peptide (BNP). Clinical analysis will consist of chart analysis floor policy but will include vital signs (blood pressure, respiratory rate, oxygen saturation, pulse), standard review of systems to assess for magnesium side effects/toxicity, and other evaluation that was clinically indicated based on patient status such as imaging if necessary. No clinical interventions will be altered by study protocol other than the determination of 12-hour or 24-hour magnesium sulfate administration post-partum. Patients will receive standard postpartum outpatient follow-up. No additional clinical visits related to the study will be necessary, and chart review will be completed until 6 weeks post-partum as that is the duration in which preeclampsia is anticipated to resolve.

Per floor policy, the magnesium bolus of 4g will already have been received prior to randomization, and the standard administration rate of 2g/hr will be continued through delivery, and into the post-partum period where the study takes place. Clinicians often adjust magnesium dosing in the setting of pulmonary edema, renal dysfunction (creatinine >1.1), or if concern presents for magnesium toxicity. If these concerns present, clinician judgement to alter magnesium dosing, or length of administration, will not be influenced.

The patient will continue in the study, with necessary annotations in the data analysis to specify these findings. Similarly, hemolysis elevated liver enzymes low platelets (HELLP) syndrome, eclampsia, persistent (non-improving) neurologic symptoms like a headache or vision change, would all necessitate 24-hour administration of magnesium given the underlying severity of the disease. The patients would be analyzed in their original group with intent-to-treat analysis.

Medical records will be abstracted to collect demographic information, medical and prenatal history, treatment course, information related to delivery and neonate after birth (Birth weight, gender, APGARS and neonatal complications). The blood samples collected during the study will be stored in a locked freezer behind locked doors in the participating laboratory. All identifiable information will be removed from the samples. All information will be de-identified and assigned unique identification codes before storing the specimens. Only the bank staff will have access to the master list that links the code to participants. All coded information in a secured computer behind locked doors. All digital information will be protected with passwords/encryption. Encryption changes the information to another format to protect it from being accessed by anyone outside of the approved staff.

Inclusion criteria

• The study population will consist of pregnant people ages 18 to 45 years old undergoing delivery in setting of preeclampsia with severe features as the experimental group and control (standard of care) groups
• Diagnosis of PreEclampsia with severe featues must be made by standard clinical guidelines based on symptoms (persistent headache not responsive to medications, persistent right upper quadrant pain not responsive to medications), laboratory values (creatinine >1.1mg/dL or twice the participants' baseline, AST or ALT > twice the upper limit of normal or twice patient's blood line, platelets <100,000), or blood pressure criteria (Systolic >160 mmHg or Diastolic >110mmHg persistent over 15 minutes such that short acting antihypertensives are required, or Systolic >160mmHg or Diastolic>110mmHg present 4 hours or more apart)

Exclusion criteria

• Exclusion criteria included Hemolysis Elevated Liver enzymes Low Platelets (HELLP) Syndrome, pulmonary edema, chronic or acute kidney injury, eclampsia, worsening neurologic symptoms, medical contraindication to magnesium (ex. Myasthenia Gravis)
• Multiple gestations (twins, triplets, etc)
• Inability to consent in English