Please select the eligibility criteria that correspond to the clinical trial below.
Title: Aspirin Supplementation for Pregnancy Indicated Risk Reduction In Nulliparas (ASPIRIN)
Brief Summary: Available data suggest that low dose aspirin may be a safe, widely available and inexpensive intervention that may significantly reduce the risk of preterm birth. However, this possibility needs to be proven in a properly designed randomized controlled trial (RCT) with preterm birth as the primary outcome. Such a clinical trial in a racially, ethnically and geographically diverse population could best be accomplished by the established infrastructure of the Global Network for Women's and Children's Health Research (GN).


Options:
A: Inclusion Criteria:

* Women experiencing one or two pregnancy losses at any point in gestation in the past that were not elective termination(s). At least one of these losses must be well documented by one of the following:

  * Sonogram demonstrating anembryonic loss, embryonic loss or fetal death.
  * Histologic confirmation of products of conception that were spontaneously passed per vagina or surgically obtained.
  * Hospital records of fetus delivery.
  * Late menses and positive serum hCG or positive urine hCG documented by hospital or clinic records followed by either a negative hospital/clinic pregnancy test or a decline in urinary hCG level over 3 days.
  * Home pregnancy tests without hCG confirmation from a healthcare provider (either serum or urine) will not be accepted.
* No more than 5 pregnancies in total including the pregnancy loss(es).\*
* Up to two prior pregnancies that did not end in a loss.\*

  \*Women may have up to two pregnancies beyond 20 weeks that were not losses, two spontaneous pregnancy losses at any time in the past, and up to one therapeutic or elective termination (two therapeutic or elective terminations if no other pregnancies). Ectopic and molar pregnancies would, for the purpose of enrollment, be considered in the same category as therapeutic termination pregnancies. Women with more than two live births or those with more than two losses, regardless of the week of gestation of the loss, are excluded.
* Presence of intact tubes (both), ovaries (both), and uterus.
* Between 18 and 40 years of age at time of baseline visit.
* Regular menstrual periods between 21 - 42 days in length (within the last 12 months). Regular menstrual periods are defined as no more than an 8-day difference between the woman's shortest and longest cycle.
* No more than one missed menses in the past 12 months (other than those missed due to pregnancy or breastfeeding).
* Actively trying to conceive with a male partner and not using contraception by the baseline visit.
* Not currently pregnant at the baseline or randomization visits.
* Ability and willingness to give informed consent.
* Willingness to be randomized and to take daily study pills for 6 months to a possible 15 months

Exclusions Criteria:

* Known allergies to aspirin or non-steroidal anti-inflammatory agents.
* Clinical indication for anticoagulant therapy. These include prior or current thrombosis, antiphospholipid syndrome (APS) or known major thrombophilia.
* Clinical indication for chronic use of NSAIDs such as rheumatoid arthritis.
* Indication for additional folic acid supplementation, such as prior infant with neural tube defect (NTD), seizure disorder.
* Medical contraindication to aspirin therapy. These include uncontrolled asthma, nasal polyps, bleeding disorders, or history of gastrointestinal ulcer.
* Presence of major medical disorders (regardless of severity). These include diabetes, hypertension, systemic lupus erythematosus (SLE), untreated or active cancer (any cancer in remission or non-melanoma skin cancer is not included in the exclusion criteria), liver disease, renal disease, rheumatoid arthritis, cardiac disease, pulmonary disease other than mild asthma, neurologic disease requiring medical treatment, uncontrolled hypothyroidism, uncontrolled seizure disorder. Untreated vitamin B12 deficiency, severe anemia (Hct \< 30%), hemophilia, gout, nasal polyps, among others.
* Currently undergoing/planned use of assisted reproductive techniques during trial (IVF; IUI; Clomid).
* History of infertility or sub-fertility. This includes any of the following:

  * No conception after ≥ 1 year of unprotected intercourse and actively trying to conceive.
  * Any prior medical treatment for infertility.
  * Prior treatment for known pelvic inflammatory disease.
  * Known male infertility or sperm abnormality (current partner).
  * Known tubal occlusion, anovulation, uterine abnormality, or endometriosis stage III or IV.
  * History of polycystic ovarian syndrome.
* Presence of unstable mental disorder. These include bipolar illness, schizophrenia, uncontrolled depression, uncontrolled anxiety disorder.
* Known current or recent alcohol abuse or illicit drug use.
* Current diagnosis of sexually transmitted infection (STI) (temporary exclusion)
B: Inclusion Criteria:

* Singleton pregnancy with a pre-pregnancy diagnosis of type I or type II diabetes of at least 6 months' duration

Exclusion Criteria:

* • Aspirin hypersensitivity (prior bronchospasm/ urticarial/ angioedema with aspirin)

  * Peptic ulcer disease
  * Known bleeding diathesis
  * Multifetal gestation
  * Severe early-onset preeclampsia in a previous pregnancy
  * Patient already on aspirin
  * Established chronic renal disease/ macroalbuminuria
  * Chronic hypertension (antihypertensive therapy in first trimester)
  * Current selective serotonin reuptake inhibitor (SSRI) use (or SSRI use within 7 days)
  * Inability to speak or read English
  * Age less than 18 years
  * Use of any other investigational medicinal product within previous 30 days
  * Presence of any illness or condition that might interfere with the patient's ability to comply with the study procedures
C: Inclusion Criteria:

* Nulliparous women.
* Ability to speak and .read English
* Singleton pregnancy at \<14 weeks.
* Willing to sign voluntarily a statement of informed consent to participate in the study.

Exclusion Criteria:

* Presence of fetal anomaly at the time of the first trimester scan
* Women with known major risk factors for pre-eclampsia who should already be on Aspirin as per National Institute of Clinical Excellence (NICE) guidance; specifically chronic hypertension, underlying connective tissue, renal or vascular disorder, type 1 diabetes mellitus.
* Under 18 years of age.
* Currently enrolled in other clinical trials.
* Contraindications to Aspirin therapy.
D: Inclusion Criteria:

* Nulliparous women between 18 - 40 years of age. Minors who are ≥ 14 years of age may be enrolled if permitted by the country's ethical guidelines.
* No more than two previous first trimester pregnancy losses
* No medical contraindications to aspirin;
* Single live intrauterine pregnancy (IUP) between 6 0/7 and 13 6/7 weeks GA corroborated by an early dating ultrasound and with presence of a heartbeat.

Exclusion Criteria:

* Women prescribed daily aspirin for more than 7 days;
* Multiple gestations;
* Fetal anomaly by ultrasound (Note most fetal anomalies are not detectable by ultrasounds done at this early gestation. Subsequent discovery of a fetal anomaly is not viewed as an exclusion.);
* Hemoglobin \< 7.0 gm/dl at screening;
* Any other medical conditions that may be considered a contraindication per the judgment of the site investigator (e.g., Lupus, Type 1 Diabetes, or any other known significant disease)
* Blood pressure ≥ 140/90 (Systolic blood pressure ≥ 140 and diastolic ≥ 90 at screening)

Answer: D