Aspirin Dose Escalation for the Prevention of Recurrent Preterm Delivery Trial

Inclusion Criteria:

* 14 years or older
* Singleton gestation. Twin gestation reduced to a singleton, either spontaneously or therapeutically, is not eligible unless the reduction occurred before 13 weeks 6 days project gestational age. Higher-order multifetal gestations reduced to singletons are not eligible.
* Gestational age at randomization between 10 weeks 0 days and 15 weeks 6 days based on clinical information and evaluation of the earliest ultrasound.
* Prior preterm birth between 20 weeks 0 days and 34 weeks 6 days with one of the following in the proximal birth reaching 20 weeks or greater:

  * Spontaneous preterm birth is defined as spontaneous preterm labor or premature rupture of membranes
  * Ischemic placental disease is defined as preeclampsia, small for gestational age, fetal growth restriction, or placental abruption, as defined clinically.
  * Stillbirth excluding those with known genetic disorders or major congenital anomalies.

Exclusion Criteria:

* Known allergy or hypersensitivity to aspirin or any medical condition where aspirin is contraindicated (e.g., history of peptic ulcer disease, nasal polyps, NSAID-induced asthma, history of gastrointestinal bleeding, known G6PD deficiency, severe hepatic dysfunction, bleeding disorders, and consumption of 3 or more alcoholic drinks per day)
* Taking other anticoagulants such as Heparin or Low-Molecular weight Heparin
* Thrombocytopenia defined as a platelet count defined as a platelet count \<100,000 microliters
* Gastric bypass surgery, regardless of type
* Aspirin use \>81 mg daily during the current pregnancy who are not willing or able to go through a 2-week washout before randomization.
* Known major Mullerian anomaly of the uterus (specifically bicornuate, unicornuate, or uterine septum not resected) due to increased risk of preterm delivery.
* Known fetal genetic disease or major malformations
* Fetal demise or planned termination of pregnancy. Selective reduction by 13 weeks 6 days gestation, from twins to singleton, is not an exclusion.
* Any fetal/maternal condition requiring invasive in-utero assessment or treatment, for example, significant red cell antigen sensitization or neonatal alloimmune thrombocytopenia.
* Patients with any of the following medical conditions because of increased risk for adverse pregnancy outcome or indicated preterm birth:

  * Treated hypertension requiring more than one agent
  * Chronic renal disease with baseline serum creatinine ≥1.5 mg/dL
  * Conditions treated with chronic oral glucocorticoid therapy (e.g., systemic lupus erythematosus)
  * Uncontrolled hyper- and hypothyroid disease
  * New York Heart Association (NYHA) stage II or greater cardiac disease
* Planned indicated delivery prior to 37 weeks.
* Participation in another interventional study that influences the primary outcome in this study (gestational age at delivery).
* Participation in this trial in a previous pregnancy.
* Delivery planned at a non-participating site