Please select the eligibility criteria that correspond to the clinical trial below.
Title: L-Arginine Treatment for Severe Vascular Fetal Intrauterine Growth Restriction: a Randomized Double Bind Controlled Trial
Brief Summary: Although there is a strong rationale to supplement gravid patients suffering intrauterine growth restriction (IUGR) or preeclampsia with Arginine or other nitric oxide donors, evidence in the literature has been inconclusive. The current study was designed to determine whether oral treatment with L-Arginine, a nitric oxide (NO) donor, would enhance birth weight and/or decrease neonatal morbidity in pregnancies with severe vascular intrauterine growth restriction (IUGR).


Options:
A: 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
B: Inclusion Criteria:

Patients were admitted to the study based on the following inclusion criteria:

1. Any age and any party.
2. Body mass index between 25 and 35.
3. Singleton pregnancy.
4. Gestational age of 24 weeks or more. Gestational age was established on the basis of menstrual dates and confirmed by first or second trimester ultrasound for booked patients, however, if a difference of \> 7 days or \> 10 days during first or second trimester respectively, then ultrasound value was used. For unbooked patients they still have the chance to be included in our study if they can bring a scan that showed gestational age during the same period mentioned before.
5. Idiopathic intrauterine growth restriction.
6. Intrauterine growth restriction due to maternal malnutrition, maternal medical disorder as anemia, pregnancy induced hypertension, or chronic renal disease.
7. Intrauterine growth restriction due to substance abuse (including smoking).
8. With or without past history of intrauterine growth restriction .

Exclusion Criteria:

1. Intrauterine growth restriction due to fetal causes as congenital abnormalities, fetal infection, or multiple gestation.
2. Any drug therapy that can affect fetal growth or fetal blood supply.
3. Maternal diseases that contraindicates the use of sildenafil citrate
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:

* 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

Answer: C