الفهرس 
PREECLAMPSIAOnly 14 pages are availabe for public view
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Abstract
P
reeclampsia is defined as new-onset hypertension after 20 weeks of gestation and proteinuria and/or any of the following:thrombocytopenia (platelets < 100,000/μL), renal insufficiency (serum creatinine > 1.1mg/dL or doubling of serum creatinine in the absence of other renal disease), impaired liver function (transaminases at twice normal concentrations in IU/L), evidence of pulmonary edema or the presence of cerebral (new onset headache) or visual symptoms/disturbances (ACOG, 2013).
Preeclampsia is associated with an imbalance of thromboxane and prostacyclin resulting in platelet activation and endothelial dysfunction (Correa et al., 2016). The efficacy of antiplatelet agents has thus been studied in the prevention of preeclampsia. In 2010, Bujold et al. published a systematic review suggesting that initiation of low-dose aspirin at < 16 weeks in women at high or moderate risk for preeclampsia significantly reduced the occurrence of preeclampsia (RR: 0.47, 95% CI: 0.34–0.65) (Bujold et al., 2010). A recent meta-analysis further supported the beneficial effects of low-dose aspirin initiated < 16 weeks. However, this study could find little to no reduction on the relative risk of preeclampsia, when aspirin was initiated after 16 weeks (Roberge et al., 2017). Although m ultiple studies have reaffirmed a benefit of aspirin in reducing the risk of preeclampsia, identifying the appropriate population to treat, when to initiate therapy, and the optimal dose of aspirin remain unclear (Correa et al., 2016).
Sildenafil is a phosphodiesterase 5 (PDE5) inhibitor, which enhances NO-mediated effects by inhibiting cyclic guanosine monophosphate degradation. During pregnancy, NO activity increases, mediating essential vascular adaptation, such as reducing maternal peripheral vascular resistance (Williams et al., 1997) and creating the low-resistance/high-caliber uteroplacental unit needed to provide adequate blood flow to the fetus (Krause et al., 2011).
Increasing NO availability during pregnancy might overcome deficits in placental and systemic NO reported in FGR and preeclampsia and thereby improve placental function and maternal endothelial function (Oyston et al., 2015). Moreover, sildenafil might counterbalance vascular dysfunction because of augmented vasoconstrictors and antiangiogenic factors (Burke et al., 2016).
Because no pronounced maternal and fetal side effects were observed in pregnant women using sildenafil for pulmonary artery hypertension, (Cartago et al., 2014).
Transition of sildenafil from preclinical to clinical studies was established for the indications FGR and preeclampsia. The first prospective studies and small clinical trials show beneficial effects of maternal oral sildenafil treatment on fetal growth (Von Dadelszen et al., 2011) and maternal blood pressure (BP) (Trapani et al., 2016) at fairly low dosages.
This study was conducted at outpatient Obstetric clinic of Ain Shams maternity hospital in the period between June 2018 and June 2019.
The patients who were fulfilling the inclusion criteria, were recruited in the study, then an informed consent was taken before starting the trial.
Detailed history was taken and careful examination was done for all patients.
Also necessary investigations as hemoglobin, blood group, RH, complete urine analysis and trans-abdominal ultrasound scan were done for patients before the study.
400 Women at gestational age of < 16 wks will be randomized into one of the following drug regime:
group I; “Sildenafil citrate plus oral low dose aspirin group “ included 200 women that will receive a 25 mg tablet of sildenafil citrate (silden 25 mg, EIPICO, EGYPT) three times daily until delivery plus 100 mg tablet of aspirin (Aspirin® Protect 100 mg, BAYER, GERMANY) once daily until gestational age of 36 wk.
group II: “Aspirin group “ included 200 women that will receive a 100 mg tablet of aspirin (Aspirin® Protect 100 mg,BAYER,GERMANY) once daily until gestational age of 36 wk.
All patients will be followed up by:
1) Measuring blood pressure;
2) laboratory investigations;
Complete blood count, urine analysis, liver function tests, and kidney function tests.
3) Ultrasonic fetal growth assessment:
The patients were informed to return to the hospital if they were complainng from right upper quadrant, epigastric pain, new-onset headache unresponsive to acetaminophen and not accounted for by alternative diagnoses or visual disturbances.
The primary outcome of this study is the incidence of preeclampsia which will be diagnosed according to the ACOG criteria.
In the total of 400 women who were recruited in the study, 25 women dropped from the study, 15 women from the first group and 10 women from the second group.
400 women were analyzed according to the intention to treat analysis. 22 women (11.0 %) developed PE from the first group and 24 women (12.0 %) from the second group with p-value 0.754 which is insignificant.
CONCLUSION &
RECOMMENDATIONS
• The addition of sildenafil citrate to low dose aspirin had no impact on the prevention of preeclampsia for women at risk of PE, in addition, sildenafil did not improve maternal and fetal outcomes.
• Sildenafil citrate prophylaxis is not recommended for prevention of PE and it should not be prescribed for this indication outside of research studies with explicit participants consent. Nevertheless, further large-scale studies are still needed to confirm our findings.
• Low-dose aspirin (100 mg/day) prophylaxis is recommended in women at high risk of preeclampsia and should be initiated between 12 weeks and 28 weeks of gestation (optimally before 16 weeks) and continued daily until delivery.
• Low-dose aspirin prophylaxis is not recommended solely for the indication of prior unexplained stillbirth, in the absence of risk factors for preeclampsia.
• Low-dose aspirin prophylaxis is not recommended for prevention of fetal growth restriction, in the absence of risk factors for preeclampsia.
• Low-dose aspirin prophylaxis is not recommended for the prevention of spontaneous preterm birth, in the absence of risk factors for preeclampsia.
• Low-dose aspirin prophylaxis is not recommended for the prevention of early pregnancy loss.