Placental Insufficiency

This study aims to evaluate the patterns of aortic isthmus Doppler in fetuses diagnosed with early fetal growth restriction (FGR) and to correlate these findings with the severity of FGR and other Doppler parameters. A cross-sectional comparative observational study will be conducted on singleton pregnant women attending the fetal medicine unit at Assiut University Hospital. Participants will be divided into two groups: fetuses with FGR and normal controls. Doppler measurements including aortic isthmus indices, uterine artery, umbilical artery, middle cerebral artery, cerebroplacental ratio, and ductus venosus will be assessed at a single time point. The study will help to clarify the clinical value of aortic isthmus Doppler in early detection and assessment of fetal compromise in FGR cases.

The goal of this proof-of-concept, case-control, clinical trial is to evaluate the efficacy of using two newer ultrasound technologies, quantitative ultrasound (QUS) and ultrafast power Doppler imaging (uPDI), to evaluate the health of the placenta, visualize blood flow through the placental vasculature by color Doppler imaging in singleton pregnancies with and without fetal growth restriction (FGR). * Our primary objective is to investigate the ability of using these ultrasound technologies to distinguish healthy pregnancies from those affected by FGR, a condition characterized by a fetal weight below the 10th percentile for the gestational age or abdominal circumference of the pregnancy. * Secondary aims include longitudinal evaluation of differences in QUS and uPDI imaging over gestation and changes in these measures with evolution of utero-placental insufficiency including with the development of abnormal umbilical-artery Doppler testing, diagnosis of severe FGR, identification of stillbirth, and detection of preeclampsia or preterm birth. Investigators will compare QUS/uPDI imaging and values in pregnancies determined to be healthy by approved, standard-of-care growth ultrasounds to those diagnosed with FGR. Participants will receive research ultrasounds with the experimental Verasonics Vantage 256 system (Verasonics, Inc, Kirkland, WA) utilizing uPDI/QUS every three weeks following their routine growth ultrasound evaluation until delivery. Demographic, obstetric, and delivery-related information, as well as portions of subjects' past medical history will be utilized by researchers to further contextualize imaging and variables gathered during the research ultrasounds.

In pregnancies with placental insufficiency, the only available treatment is close monitoring to determine the point at which the risks of preterm birth for the baby are lower than the risks of continuing the pregnancy. Therefore, safely prolonging pregnancy is the current management goal for this condition. Statins, such as pravastatin, are approved and marketed drugs used to prevent cardiovascular disease. Recent studies suggest that statins may help treat pregnancy complications and prolong pregnancy, thereby avoiding extreme prematurity and improving long-term health outcomes for both mother and baby. Previous clinical trials have shown the ability of statins to stabilize angiogenic factors, thus reducing obstetric complications associated with placental insufficiency. In 2015, a study reported that pravastatin was effective in stabilizing blood pressure and reducing proteinuria associated with preeclampsia. More recently, in 2020, it was demonstrated that in pregnant women with fetal growth restriction treated with pravastatin, the sFlt-1/PlGF ratio was lower than in untreated women, indicating a slower progression of placental insufficiency. This study proposes administering a daily dose of 40 mg of pravastatin between 24 and 29.6 weeks of gestation to mothers diagnosed with preeclampsia and/or fetal growth restriction. One group of women will receive the medication, while another group will receive a visually identical but inactive pill (a placebo), allowing us to determine whether any observed improvement in pregnancy is attributable to the medication. Assignment to the treatment or placebo group will be random, and neither the mothers nor the healthcare professionals caring for them will know which group they are in. The investigators also aim to examine whether this intervention during pregnancy protects the cardiovascular system. For this reason, the investigators will assess both the mother and the baby six months after birth using an ultrasound of the heart and blood vessels, and the investigators will also perform a blood test on the mothers. Additionally, the investigators want to explore the needs and expectations of women who experience these complications during pregnancy and postpartum, so that their stories can guide us in finding answers and solutions that are as personalized as possible to the real needs of families. After the visit at six months postpartum, yhe investigators will follow up with annual phone calls over the next four years to check on the participants' health and their baby's. During each call, the investigators will review the participant's health status and talk about how the participant is feeling. All of this will help us ensure that the treatment does not cause any long-term issues and will improve future care for other mothers and babies. A total of 154 pregnant women are expected to be included in order to meet the study's objectives.

This is a prospective observational study with the goal of developing and assessing a predictive model of placental insufficiency.

An essential part of clinical research is the availability and accessibility of human biospecimens for the identification of biomarkers, new treatments and measurement of response to therapy. Proteins, RNA and DNA can be extracted and studied as well. This is a critical first step in performing many fundamental molecular biology experiments. A variety of biospecimens are utilized for research including but not limited to normal and malignant tissues, blood, and other body fluids. In order to obtain high-quality biospecimens, they must be acquired serially, stored according to current standards, and matched with clinical information for maximum value. As such, the investigators would like to create a repository of biospecimens collected from pregnant patients who are seen at Mount Sinai Hospital and other research hospitals in Toronto. Mount Sinai provides personnel and infrastructure to serve the largest (7500 births/year) and highest complex Maternity program in Ontario. Of the 7500 patients a year, at least 2500 are considered high risk pregnancies, where there's a possibility of preeclampsia, placenta accreta and a host of other complications. For this study, biological specimens - blood, cervical and placental samples - will be collected from these high-risk groups in order to better understand the causes of the underlying conditions.

In this project there are 2 time points during the pregnancy included, namely at 21 weeks and 30 weeks of gestation, to measure the predictive values of FGR, strain and strain rate. The fetal growth parameters will be collected at the same time points, to define the growth (differences) throughout gestation of both fetuses. A maternal blood sample will be taken at 21 weeks of gestation to identify the level of exposure to air pollution (black carbon) and the level of biochemical markers of placental dysfunction. Doppler ultrasounds will be used for antenatal identification of placenta insufficiency. At birth, umbilical cord blood and the placenta will be collected. The placenta will be examined, to identify morphological findings which are associated with FGR. The umbilical cord blood and placental biopsy will be used for the level of exposure to air pollution and the level of oxidative stress. One to three days after birth, neonatal strain and strain rate will be measured to define postnatal cardiac remodeling as well as the neonatal blood pressure as cardiovascular risk factor.