Please select the eligibility criteria that correspond to the clinical trial below.
Title: Pentaerithrityltetranitrat (PETN) Zur Sekundärprophylaxe Der Intrauterinen Wachstumsretardierung
Brief Summary: Approximately 10% of all pregnancies experience mal perfusion of the placenta resulting in fetal growth restriction (FGR) of the fetus. FGR is the most important cause of perinatal mortality and morbidity. Impaired placental function determined by insufficient transformation of the uterine arteries and mal-perfusion of the placenta is the leading cause of FGR. So far, there is no treatment option for pregnancies complicated by FGR and the clinical management is restricted to close monitoring, assessing for the optimal time point of delivery of the fetus threatened by intrauterine death. In a pilot study a risk reduction of 38% for the development of severe FGR and FGR or death could be demonstrated by giving the organic nitrate pentaerithrityl-tetranitrate (PETN) to patients recognized at risk for FGR by impaired uterine artery Doppler at mid gestation (Schleussner, 2014). To confirm these results this prospective randomized placebo controlled double-blinded multicentre trial, was initiated.


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:

* abnormal uterine artery Doppler at 19+0 to 22+6 weeks of gestation, defined by a mean pulsatility index (PI) Exceeding 1.6
* singleton pregnancy
* age\>/= 18 years
* informed consent

Exclusion Criteria:

* known fetal chromosomal or suspected major structural defects at time of enrollment
* premature rupture of membranes at time of enrolment; maternal disease defined as contraindication for intake of PETN
* anamnestic known insensitivity to Pentalong® or its ingredients or to medications with similar chemical structure
* participation of the patient in another clinical trial (parallel or within the waiting period of a previous clinical trial)
* multiple pregnancy

Answer: D