Please select the eligibility criteria that correspond to the clinical trial below.
Title: The Dutch STRIDER (Sildenafil TheRapy In Dismal Prognosis Early-onset Fetal Growth Restriction)
Brief Summary: Rationale: Severe, early-onset fetal growth restriction (FGR) due to placental insufficiency is associated with a high risk of perinatal morbidity with long-lasting sequelae and mortality. Placental insufficiency is the result of abnormal formation and function of the placenta (placentation) with inadequate remodelling of the maternal spiral (uteroplacental) arteries. There is currently no therapy available with demonstrated effectiveness. Evidence suggests Sildenafil citrate improves uteroplacental blood flow, growth, and meaningful outcomes.

Objective: To evaluate the effectiveness of sildenafil (versus placebo) in achieving healthy perinatal survival.

Study design: Multicenter nationwide randomized placebo-controlled clinical trial.

Study population: Women with a singleton pregnancy between 20 and 30 weeks with severe fetal growth restriction of likely placental origin, and with estimated significant likelihood of perinatal death.

Intervention: Sildenafil 25mg or placebo tablet orally three times daily. Main study parameters/endpoints: Perinatal healthy survival, i.e. survival without severe neonatal morbidity at term age.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Taking tablets three times daily. No additional ultrasounds, other than standard clinical protocol, one extra blood sample at inclusion. No risks anticipated, unexpected medication-associated risks can't be excluded on beforehand.


Options:
A: Inclusion Criteria:

* Gestational age from 18+0 - 27+6 weeks

AND

* EO IUGR, defined as

  1. ultrasound (U/S) measurement of the fetal abdominal circumference (AC) \<10th percentile for gestational age and/or documented reduced fetal growth velocity complicating either a prior EO IUGR with adverse perinatal outcome or abnormal uterine artery waveform in the index pregnancy;

     OR
  2. U/S estimate of fetal weight (EFW) \<700g

AND

* Serum PlGF \< 5th percentile for gestational age

Exclusion Criteria:

* known fetal aneuploidy
* known fetal anomaly/syndrome/congenital infection confirmed at the time of enrolment
* decision made to terminate pregnancy
* current cocaine or vasoconstrictor use (e.g. crystal meth) (risk of acute cardiac events)
* contraindication to sildenafil therapy, e.g. known significant maternal cardiac disease, left ventricular outflow tract obstruction, concomitant treatment with nitrates or previous allergy to sildenafil
* known HIV positive status (due drug-drug interaction between sildenafil and antiretrovirals)
* receiving peripheral alpha-blockers (e.g. prazosin)
* prior participation in a STRIDER trials
* pre-eclampsia or gestational hypertension diagnosed
B: Inclusion Criteria:

Inclusion criteria ((I OR II) AND III):

* At 20+0-27+6 weeks: an ultrasound measurement of the fetal abdominal circumference (AC) \<3rd percentile for gestational age or an ultrasound estimate of fetal weight (EFW) \<5th percentile OR
* At 28+0-29+6 weeks: an ultrasound estimate of fetal weight (EFW) \<700 grams using Hadlock C formula AND
* Likely placental origin defined by (a AND/OR b AND/OR c AND/OR d)

  * The presence of uterine artery notching
  * Abnormal flow velocity patterns of the umbilical artery or middle cerebral artery
  * Maternal hypertensive disorders
  * Low PlGF in point-of-care assessment

Exclusion Criteria:

* Plan to terminate pregnancy for maternal or fetal indication within days
* Known multiple pregnancy
* Identified congenital anomalies or congenital infection
* Maternal age at eligibility \<18 years
* Cocaine use
* Current use of sildenafil
* Current use of cyp3A5 inhibitors: amiodaron, azitromycine, ciclosporine, claritromycine, diltiazem, erytromycine, fluconazol, itraconazol, ketoconazol, verapamil, voriconazol.
* Recent myocardial infarction or stroke
C: Inclusion Criteria:

* Multicenter randomized trial.
* Patients with a singleton pregnancy with IUGR defined by fetal abdominal circumference less than or equal to the third percentile for gestational age, and abnormal uterine Doppler. Uterine Doppler was considered pathologic if Pourcelot's resistance index (S-D/S) was equal to or higher than 0.7, and/or if an obvious notch was present. If the placenta was not median, the side of the pathologic Doppler had to be on the same side as the placenta

Exclusion Criteria:

* Acute fetal distress
* Non vascular and non severe IUGR (normal uterine doppler scans and/or abdominal circumference \> 3rd percentile)
* Maternal immune disorder
* IUGR from an infectious etiology
* IUGR associated with fetal malformation, multifetal pregnancy, and preeclampsia upon inclusion
D: Inclusion Criteria:

* Subjects with pre-eclampsia defined as new hypertension with a diastolic BP of \> or = 90 mmHg on two occasions separated by at least 4 hrs arising after 20 weeks of pregnancy, associated with \>500 mg/24 hr proteinuria. Subjects with pre-existing hypertension (on treatment) need only fulfill proteinuria requirement.
* Gestational age 24-34 w
* Singleton pregnancy

Exclusion Criteria:

* Where urgent delivery is indicated
* Where the fetus is suspected to have a structural or chromosomal abnormality

Answer: B