The participants will be pregnant women with late-onset pre-eclampsia

Pre-Eclampsia

On admission, the blood samples of consenting participants will be collected and analysed using enzyme linked immunosorbent assay technique to determine the level of PlGF (pg/ml).

Placental growth factor

Alex Ekwuueme Federal University Teaching Hospital

Placental Growth Factor as a Predictor of Adverse Pregnancy Outcomes in Preeclamptic Women

Placental Growth Factor as a Predictor of Adverse Pregnancy Outcomes in Preeclamptic Women in Abakaliki

Adverse maternal outcomes will include one or more of: disseminated intravascular coagulation (DIC), HELLP syndrome, abruptio placentae, pulmonary oedema, intracerebral haemorrhage, acute left ventricular failure, renal insufficiency (creatinine >90 umol/l), liver disease (aspartate aminotransferase >40 U/l), eclampsia and maternal death.

Adverse fetal outcomes will include one or more of: Apgar score <7 at the 5th minute, small-for-gestational-age infant (SGA; <10th centile), admission to special-care nursery, fetal death and early neonatal death.

The researchers plan to make the data available to other authors

Johnbosco Ifunanya Nwafor

Principal investigator

Hypertension (>140 mmHg systolic or >90 mmHg diastolic) developing after 20 weeks gestation and the coexistence of one or more of the following new onset conditions:
Proteinuria (>300 mg/day)
Other maternal organ dysfunction
renal insufficiency (creatinine >90 μmol/L)
liver involvement (elevated transaminases - and/or severe right upper quadrant or epigastric pain)
neurological complications (eclampsia, altered mental status, blindness, stroke, hyperreflexia when accompanied by clonus, severe headaches when accompanied by hyperreflexia, persistent visual scotomata)
hematological complications (thrombocytopenia, disseminated intravascular coagulation, hemolysis)
Uteroplacental dysfunction

New onset of hypertension (>140 mmHg systolic or >90 mmHg diastolic) after 20 weeks gestation, without proteinuria, in a previously normotensive woman.

Babies born alive before 37 weeks of pregnancy are completed.

Moderate IUGR is an estimated fetal weight and / or abdominal circumference < 10th percentile for its gestational age Severe IUGR is an EFW (estimated fetal weight) and/ or AC (abdominal circumference) < 5th percentile for its gestational age

Pregnancy Complications

Endothelial Dysfunction

University Hospital Antwerp

Oxidative Stress and Endothelial Function in Pregnancy Complications

Oxidative Stress and Endothelial Function in Pregnancy Complications: Development of a New Screening Algorithm

Single center prospective longitudinal study: To evaluate the oxidative stress profile in normal pregnancies.
Multicenter matched case-control study: To compare the oxidative stress profile in normal versus complicated pregnancies.

Single center prospective longitudinal study: To evaluate endothelial function in normal pregnancies.
Multicenter matched case-control study: To compare endothelial function in normal versus complicated pregnancies.
To relate endothelial function (using Endopat ®) to nitric oxide/eNOS/superoxide concentration (using EPR and Western Blotting).

Single center prospective longitudinal study: To evaluate arterial stiffness in normal pregnancies.
Multicenter matched case-control study: To compare arterial stiffness in normal versus complicated pregnancies.
To relate Arterial stiffness (using Sphygmocor ®) to nitric oxide/eNOS/superoxide concentration (using EPR and Western Blotting).

Pregnancy outcome will be determined using the diagnostic criteria described in 'groups and interventions'.
Single center prospective longitudinal study and multicenter matched case-control study.
To relate oxidative stress profile to pregnancy outcome.

Single center prospective longitudinal study and multicenter matched case-control study.

Prof Yves Jacquemyn

Professor

Universiteit Antwerpen

University Hospital, Antwerp

Ziekenhuis Oost-Limburg

Maastricht University Medical Center

Erasmus Medical Center

After signing an informed consent form and filling a demographic and medical questionnaire, a randomization 1:1 will be carried. 50 women will be in the control arm. the group will be treated according to ACOG guidelines (Appendix). After the delivery, a small placenta sample will be collected.
Control group will be treated with placebo.

50 women will be in the treatment arm. the group will be treated according to ACOG guidelines (Appendix). After the delivery, a small placenta sample will be collected. In addition, following randomization experimental group will be treated with Rosuvastatin 40mg that will be administrated orally with or without food. Treatment will be carried within the first hour following delivery. Another dose will be given 24 hours after first administration. Control group will be treated with placebo.

Severe Pre-eclampsia

Rosuvastatin is a hydrophilic statin, short treatment (hours to days) with this type of statin improved the outcome of patients during acute myocardial infarction, sepsis, contrast-induced nephropathy, hepatic ischemia/reperfusion injury, emphasizing its preferential pleiotropic effects. Currently, the FDA classiﬁes all statins as pregnancy category X and discourages their use during pregnancy due to higher abortion rate and teratogenicity that were observed in animals exposed to hydrophobic statins during pregnancy. Since the use of statins after delivery is allowed, the present study will aim to evaluate whether Rosuvastatin may accelerates preeclampsia resolution following delivery and potentially reduce postpartum preeclampsia complications.

Rosuvastatin

Placebo

Rosuvastatin in Order to Induce Preeclampsia Resolution in Severe PET up to 48 Hours Following Delivery

Rosuvastatin Use in Order to Induce Preeclampsia Resolution in Severe Preeclampsia Cases up to 48 Hours Following Delivery

systolic pressure below 140mm\Hg or diastolic pressure below 90mm\Hg. Measurement will be carried out according to standard Protocol: before delivery, every 30 minutes during the first 2 hours post-delivery then every hour until discharge.

We intend to test the following metrics:
The amount and activity of NK cells in the placenta.
The rate of secretion of angiogenic factors VEGF, SFLT-1, PLGF and inflammation factors TGF-ALFA I and IL-6.

Ofer Beharier

Physician at Obstetrics and Gynecology Division

Soroka University Medical Center

One group of 12 subjects, each under 4 conditions (each phase is 4 weeks)

LNAA, washout, Kuvan, and LNAA+Kuvan
One group of 10 subjects, each under 4 conditions (each phase is 4 weeks)
Kuvan: Dosed at 20 mg/kg; PO; Phase 3, Phase 4
Large Neutral Amino Acid Therapy: Dosed by weight: weight x .5 = total tablets per day; PO; Phase 1, Phase 4; taken with food

All Study Participants

Gender

Region of Enrollment

Evaluated for each subject under 4 conditions (washout, LNAA only, Kuvan only and LNAA+Kuvan)

LNAA
Large Neutral Amino Acid Therapy: Dosed by weight: weight x .5 = total tablets per day; PO; Phase 1, Phase 4; taken with food

LNAA

no Kuvan or LNAA or any medical food products. Limited protein intake diet.

Washout

Kuvan (BH4): Dosed at 20 mg/kg; PO; Phase 3, Phase 4

BH4 (Kuvan)

Kuvan: Dosed at 20 mg/kg; PO; Phase 3, Phase 4
Large Neutral Amino Acid Therapy: Dosed by weight: weight x .5 = total tablets per day; PO; Phase 1, Phase 4; taken with food

BH4 and LNAA

Serum Melatonin at the End of 4 Weeks

Urine 6-sulfatoxymelatonin at the End of 4 Weeks

Urine Dopamine at the End of 4 Weeks

LNAA (4 Weeks)

Washout (4 Weeks)

BH4 Therapy (4 Weeks)

BH4 and LNAA (4 Weeks)

Shoji Yano

Phenylketonuria (PKU)

Kuvan

Dosed by weight: weight x .5 = total tablets per day; PO; Phase 1, Phase 4; taken with food

Large Neutral Amino Acid Therapy

Keck School of Medicine, Clinical Trials Unit at Keck Medical Center of USC

Effects of Kuvan on Melatonin Secretion

Pilot Study to Evaluate Melatonin Secretion as a Marker of Decreased Serotonin in Individuals With PKU: Evaluation of the CNS Effects of Tetrahydrobiopterin

hemolysis/tyrosine

Placental Growth Factor as a Predictor of Adverse Pregnancy Outcomes in Preeclamptic Women

Oxidative Stress and Endothelial Function in Pregnancy Complications

Rosuvastatin in Order to Induce Preeclampsia Resolution in Severe PET up to 48 Hours Following Delivery

Effects of Kuvan on Melatonin Secretion

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