Using Placental Pathology to Prevent Recurrent Adverse Pregnancy Outcomes: a Pilot Project

The goal of this randomized clinical trial is to evaluate if we can use placental pathology in a prior pregnancy which had an adverse outcome, such as early delivery, stillbirth, a baby born smaller than expected, or severe forms of high blood pressure during pregnancy, to guide treatment in the subsequent pregnancy and reduce risk of recurrent adverse pregnancy events.

The main questions it aims to answer are:

* Whether enoxaparin prevents recurrent adverse pregnancy outcomes among patients with a prior adverse pregnancy outcome that occurred in the setting of maternal vascular malperfusion (MVM).
* If enoxaparin reduces the occurrence or severity of MVM among patients with a prior adverse pregnancy outcome that occurred in the setting of MVM.

In this clinical trial, participants will undergo consent, blood samples will be collected, and participants will be randomized in a 1:1 ratio to the enoxaparin or control groups at their first study visit.

* Participants will return for a study visit within 1 week following randomization.
* If assigned to the enoxaparin, the participant will be asked to take a dose of the enoxaparin once a day (40 mg daily) daily from 12 0/7 weeks and/or the start of enrollment (whichever is later) and continue until 36 weeks gestational age, after which enoxaparin will be discontinued.
* Participants in the control group will have care as usual, with no additional medications.
* During this study, a study team member will collect a blood sample from all participants at 20-24 weeks, 32-34 weeks, and at delivery.
* Participants in the enoxaparin group will have their blood work checked a week after starting medication to ensure that they have no unanticipated side effects.

Researchers will compare the enoxaparin group to the control group to see if enoxaparin prevents or reduces the occurrence or severity of maternal vascular malperfusion (MVM) among patients with a prior adverse pregnancy outcome.

Eligibility Criteria:
Eligibility Criteria:

Inclusion (must meet all three criteria):

1. Subjects with a prior adverse outcome in a prior pregnancy. Adverse outcome is defined as prior singleton preterm birth ( \< 37 weeks), SGA infant (defined as birthweight \< 10th percentile), preeclampsia with severe features, or stillbirth (fetal demise after 20 weeks gestation), as certified by an obstetrician
2. Patients with maternal vascular malperfusion on pathology from pregnancy with prior adverse pregnancy outcome, as certified by a perinatal placental pathologist
3. Current singleton pregnancy at \<16 6/7 weeks gestational age.

Exclusion Criteria:

1. Anticoagulation planned for current pregnancy (including warfarin, enoxaparin, heparin)
2. Known major fetal anomaly
3. Contraindication to enoxaparin: Specifically active major bleeding, known thrombocytopenia (platelets \<100), hypersensitivity to enoxaparin sodium, hypersensitivity to heparin or pork products, hypersensitivity to benzyl alcohol
4. Chronic kidney disease with eGFR\< 60
5. Known chronic liver disease with baseline AST/ALT \> 3 x upper limit of normal
6. Subjects with mechanical prosthetic heart valves